J Cancer [JOURNAL]
Sun
200 papers
Inflammation Drives Phosphorylation and Acetylation of MutS Homolog 3 and Interaction with Cytosolic HDAC6.
Tseng-Rogenski SS, Koi M, Carethers JM
J Cancer · 2026 · PMID 42038019 · Full text
BACKGROUND: MutS Homolog 3 (MSH3), part of the MutSβ DNA mismatch repair complex with MSH2, can reversibly translocate from the nucleus to cytosol via IL-6 signaling, abrogating nuclear MutSβ function and is associated w...
BACKGROUND: MutS Homolog 3 (MSH3), part of the MutSβ DNA mismatch repair complex with MSH2, can reversibly translocate from the nucleus to cytosol via IL-6 signaling, abrogating nuclear MutSβ function and is associated with metastasis and poor patient survival. A polymorphism consisting of deletion of 27-bp proximate to the nuclear localization signal (NLS) (Δ27bpMSH3) allows MSH3 cytosolic retention with IL-6 or oxidative stress. Here, we examined for IL-6-induced post-translational modifications associated with MSH3 cytosolic translocation. METHODS: We utilized MSH3-genotyped colon cancer cell lines after IL-6 treatment to assess post-translational modification of MSH3 via Western blots (WB). We modified sequences within the MSH3-NLS-EGFP reporter construct to assess MSH3 localization via immunofluorescent microscopy and WB after nuclear-cytosolic fractionation. Immunoprecipitation (IP) followed by WB was used to study post-IL-6-induced interactions with MSH3. RESULTS: MSH3 and Δ27bpMSH3 increased serine phosphorylation after 2 hours followed by tyrosine phosphorylation 18 hours post IL-6 treatment, with Δ27bpMSH3 showing more robust phosphorylation than MSH3 likely due to increased cytosolic translocation. MSH3 cytosolic localization was enhanced by acetylation of lysine residues within MSH3's NLS, specifically at residues K, K and K. With the observed acetylation control for MSH3 cytosolic localization, IP experiments demonstrate binding of cytosolic-located histone deacetylase 6 (HDAC6) to acetylated Δ27bpMSH3. CONCLUSIONS: Polymorphic MSH3 undergoes serine/tyrosine phosphorylation and NLS acetylation upon IL-6 signaling for its nuclear-cytosolic shift and binds HDAC6 in the cytosol which may contribute to anticipated deacetylation and MSH3 protein stability when separated from MSH2. These modifications might be targeted to regulate MSH3's intracellular localization.
Impact of Sarcopenia and Serum Creatinine on Clinical Outcomes after Tace in Hepatocellular Carcinoma.
Rossetto A, De Re V, Montaldo L … +8 more , Bresadola V, Zompicchiatti A, Sponza M, Piccolo D, Soardo G, Battista S, Mangogna A, Uzzau A
J Cancer · 2026 · PMID 42038018 · Full text
BACKGROUND: Transarterial chemoembolization (TACE) is the standard treatment for intermediate unresectable hepatocellular carcinoma (HCC); however, reliable prognostic markers are still lacking. Sarcopenia has been propo...
BACKGROUND: Transarterial chemoembolization (TACE) is the standard treatment for intermediate unresectable hepatocellular carcinoma (HCC); however, reliable prognostic markers are still lacking. Sarcopenia has been proposed as a negative prognostic factor in HCC, but its impact on TACE outcomes remains unclear. METHODS: We retrospectively analyzed 48 HCC patients treated with TACE or transarterial embolization (TAE) at our institution (between 2013 and 2020). Sarcopenia was assessed on computed tomography (CT) or magnetic resonance imaging (MRI) scans at baseline, one month, and six months after treatment according to RECIST criteria. RESULTS: At six months, 27 patients (61.4%) achieved complete or partial response, while 17 (38.6%) experienced stable or progressive disease; four patients were excluded due to missing follow-up data. Sarcopenia was more frequent among responders, increasing from 13.5% at baseline to 22.2% in 6 months, while it was initially absent in non-responders. Conversely, non-responders showed a later increase in sarcopenia (0% at baseline to 29.6% at 6 months), suggesting that late sarcopenia might reflect treatment-related metabolic changes. Overall, the prevalence of sarcopenia increased during follow-up. New-onset sarcopenia was more frequent in non-responders and was associated with lower serum creatinine levels , suggesting a possible link between treatment-related muscle loss and poor therapeutic response. Kaplan-Meier showed that smoking status was associated (p = 0.01) with poorer response at 6 months (), while sarcopenia and low creatinine levels showed borderline associations (p = 0.095). CONCLUSION: In this exploratory study, baseline CT-defined sarcopenia was not significantly associated with short-term response to TACE. However, treatment-related sarcopenia with low creatinine levels may reflect frailty during follow-up, and poorer therapeutic response. Given the small sample size and limited number of sarcopenic patients, these findings should be considered hypothesis-generating and require validation in larger prospective studies.
Prior Cancer among Men Diagnosed with Breast Cancer is Associated with Worse Overall Survival but Equivalent Breast Cancer-Specific Survival.
Rathod A, Murphy CC, Shahan KL … +1 more , Pruitt SL
J Cancer · 2026 · PMID 42038017 · Full text
BACKGROUND: Men newly diagnosed with breast cancer (BC) who have survived prior cancer are often excluded from clinical trials, despite limited evidence on how prior cancer impacts BC outcomes. Understanding survival of...
BACKGROUND: Men newly diagnosed with breast cancer (BC) who have survived prior cancer are often excluded from clinical trials, despite limited evidence on how prior cancer impacts BC outcomes. Understanding survival of those with prior cancer is crucial for trial sponsors and investigators to make informed eligibility decisions. Using Surveillance, Epidemiology, and End Results (SEER) data, we investigated the impact of prior cancer on survival in men diagnosed with BC between 2011 and 2015. METHODS: We evaluated the prevalence of prior cancer of a different type in adult men with BC and analyzed its effects on overall and BC-specific survival using Cox models and the Fine and Gray method to account for competing risks of death. Models adjusted for covariates including patient, tumor, and treatment factors. RESULTS: Among 1,923 men with BC, 241 (12.5%) had a prior cancer of different type. There were 904 deaths from any cause including 365 from BC. Median overall survival was 10.1 years. Adjusted models demonstrated worse overall survival for men with prior cancer (HR=1.3, 95% CI: 1.1, 1.6) but no statistically significant difference in BC-specific survival (sdHR=0.9, 95% CI: 0.7, 1.4) between the groups. CONCLUSIONS: Despite worse overall survival, men with prior cancer did not have worse BC-specific survival, suggesting their inclusion in trials is unlikely to introduce bias in BC-specific survival. IMPLICATIONS FOR CANCER SURVIVORS: Including men with prior cancer in trials may enhance trial accrual, inclusivity, and generalizability, critical aspects of research studies for this rare cancer in which accrual is already a challenge.
Myeloid-Derived Suppressor Cells and Radiotherapy: Regulation and Clinical Implications.
Yang L, Wang K, Zeng W … +4 more , Lu Y, Sheng H, Xiong H, Zhang H
J Cancer · 2026 · PMID 42038016 · Full text
Radiotherapy (RT) serves as a critical treatment modality for cancer, which not only destroys local tumor cells, but also exerts the "double-edged sword" impact on the immune system. While triggering anti-tumor immune re...
Radiotherapy (RT) serves as a critical treatment modality for cancer, which not only destroys local tumor cells, but also exerts the "double-edged sword" impact on the immune system. While triggering anti-tumor immune response, RT also induces a great number of immunosuppressive cells, including a predominant cell population, myeloid-derived suppressor cells (MDSCs). Notably, the RT-induced MDSCs play a vital role in radioresistance. To enhance the efficacy of RT, numerous preclinical studies have elucidated the mechanisms by which RT modulates MDSCs, and evaluated the MDSC-targeted strategies to sensitize RT. Moreover, some clinical studies have explored drugs involved in MDSC-targeting to enhance the effectiveness of RT. However, though generally tolerable, the clinical benefits of combining these agents with RT are limited. Lacking specificity of MDSC-targeted agents is a major concern. Furthermore, several fundamental challenges complicate the investigation of MDSCs and their interplay with RT. These include the lack of specific biomarkers for MDSCs, their dynamic behavior during RT, differences between murine and human immune systems, the complexity of standard-of-care regimens, and the involvement of other immunosuppressive cell populations. Future investigations need to keep focusing on uncovering the features of MDSCs and their roles in RT, so that we can develop specific therapies to target MDSCs individually. This review covers the complicated regulatory network between RT and MDSCs, as well as current preclinical and clinical strategies targeting MDSC to sensitize RT, aiming to provide some insights and directions for cancer therapy.
High PMS2 Expression-Based Nomogram for Risk Stratification in Resected Hepatocellular Carcinoma: Application to Recurrence and Neoadjuvant Therapy Selection.
Gong W, Han R, Sun L … +8 more , Gao Y, Han Z, Wang Y, Xia Y, Wei Y, Song T, Chen L, Tian X
J Cancer · 2026 · PMID 42038015 · Full text
Hepatocellular carcinoma (HCC) progresses rapidly with a poor prognosis due to the lack of reliable recurrence risk markers. Accurate prognostic stratification and individualized recurrence prediction remain major clinic...
Hepatocellular carcinoma (HCC) progresses rapidly with a poor prognosis due to the lack of reliable recurrence risk markers. Accurate prognostic stratification and individualized recurrence prediction remain major clinical challenges, hindering treatment optimization, particularly for adjuvant or neoadjuvant therapy. Although defects in mismatch repair (MMR) mechanisms are well studied, the role of elevated MMR protein expression-particularly post-meiotic segregation increased 2 (PMS2)-has remained unclear. This study aimed to investigate the prognostic value of PMS2 overexpression and develop an integrated predictive model to improve risk stratification and guide therapy selection. We analyzed 173 HCC patients and demonstrated that elevated PMS2 expression was significantly associated with poorer disease-free survival (DFS) ( < 0.001) and overall survival (OS) ( < 0.001). Cellular and animal models confirmed the pro-proliferative role of PMS2 in HCC progression. Multivariate analysis identified high PMS2 expression [HR: 3.109 (2.019-4.786), < 0.001], high Phosphorylated-Protein Kinase B (p-AKT) expression [HR: 2.201 (1.304-3.715), = 0.003], Barcelona Clinic Liver Cancer (BCLC) stage [HR: 2.635 (1.156-5.992), = 0.021], and poor pathological differentiation [HR: 1.729 (1.098-2.722), = 0.018] as independent risk factors for poor DFS. The nomogram based on these factors demonstrated good predictive performance and effectively stratified patients into high-risk and low-risk groups ( < 0.001). In an exploratory analysis of a separate cohort receiving neoadjuvant immunotherapy, preliminary data suggested that high-risk patients might derive greater survival benefit (p=0.044). These findings highlight PMS2 overexpression as a potential prognostic biomarker and provide a promising predictive tool for personalized treatment planning in HCC, warranting further validation in prospective studies.
Integrative Multi-Omics and Single-Cell Profiling Identify Chitinase Domain Containing Protein 1 (CHID1) as a Prognostic Biomarker in Glioblastoma.
Kumar S, Wu CC, Solomon DD … +10 more , Ngadio JL, Xuan DTM, Ko CC, Palekkode N, Fathima A, Lin HY, Lin HR, Wang CY, Lee YK, Nguyen NUN
J Cancer · 2026 · PMID 41869455 · Full text
Glioblastoma multiforme (GBM), the most aggressive primary brain tumor, is characterized by high recurrence, metabolic plasticity, and complex tumor microenvironmental interactions. The human chitinase and chitinase-like...
Glioblastoma multiforme (GBM), the most aggressive primary brain tumor, is characterized by high recurrence, metabolic plasticity, and complex tumor microenvironmental interactions. The human chitinase and chitinase-like protein family includes five members (CHI3L1, CHI3L2, CHIA, CHID1, and CHIT1) that share conserved chitinase-related domains but exhibit diverse biological functions in immune regulation and tissue remodeling. While chitinase-like proteins are recognized as mesenchymal-associated markers, however, the role of CHID1 in GBM remains largely unexplored. An integrative multi-omics strategy combining TCGA-GBM and CGGA transcriptomic datasets, single-cell RNA sequencing, and enrichment analyses (GSEA, GO, KEGG, and MetaCore) were used to investigate CHID1 expression patterns and associated transcriptional programs. Pharmacogenomic correlations and molecular docking were used to explore potential drug-response associations. CHID1 showed higher expression in GBM compared to the normal brain and was associated with poor overall survival. A single-cell analysis showed tumor-associated expression patterns of CHID1 across malignant samples. Pathway enrichment analyses identified transcriptional programs related to oxidative phosphorylation, redox-related processes, DNA repair, and cell cycle pathways. Collectively, this study provides a comprehensive multi-cohort and multi-modal characterization of CHID1 expression in GBM, integrating bulk transcriptomics, single-cell RNA sequencing, and tissue-level validation. The findings establish CHID1 as a GBM-associated transcriptional marker linked to metabolic and redox-related programs and provide a systematic resource for future investigations into chitinase family-related biology in GBM.
FBXW7 suppresses cell proliferation, migration, and epithelial-mesenchymal transition in endometrioid ovarian carcinoma.
Tsai CC, Hsu CY, Suen JL … +5 more , Tu HP, Tsai KB, Huang SC, Ou YC, Tsai EM
J Cancer · 2026 · PMID 41869454 · Full text
Epithelial ovarian carcinoma is a common gynecologic malignancy. Evidence from several studies suggests that subtypes of this cancer-specifically clear-cell ovarian carcinoma and endometrioid ovarian carcinoma (ENOC)-are...
Epithelial ovarian carcinoma is a common gynecologic malignancy. Evidence from several studies suggests that subtypes of this cancer-specifically clear-cell ovarian carcinoma and endometrioid ovarian carcinoma (ENOC)-are associated with endometriosis. FBXW7 (F-box and WD repeat domain containing 7) is a tumor suppressor and component of an E3 ubiquitin ligase complex, which is responsible for tagging proteins for proteasomal degradation. FBXW7 is one of the most frequently dysregulated proteins of the ubiquitin-proteasome system in various human cancers. Thus, we investigated whether FBXW7 dysfunction contributes to epithelial ovarian carcinoma. We found that the level of FBXW7 was lower in endometriosis-associated ovarian carcinoma, especially ENOC. Functional assays revealed that overexpression of FBXW7 inhibited the proliferation and migration of ovarian carcinoma cells, whereas FBXW7 knockdown had the opposite effect. We also found that FBXW7 expression was associated with reduced vimentin levels, accompanied by changes in epithelial-mesenchymal transition (EMT) markers. Overexpression of FBXW7 increased E-cadherin levels while reducing N-cadherin and vimentin levels, thereby promoting the epithelial phenotype. Conversely, FBXW7 knockdown upregulated vimentin and N-cadherin levels, facilitating EMT. Co-immunoprecipitation assays indicated that FBXW7 co-precipitates with vimentin, suggesting a possible role for FBXW7 in influencing vimentin abundance. These findings highlight FBXW7 as a potential tumor suppressor in endometriosis-associated ovarian carcinoma, with effect on cell proliferation, migration, and EMT regulation. The FBXW7-vimentin association may represent previously unrecognized pathway with therapeutic relevance in ovarian carcinoma.
Recurrence of Adult Granulosa Cell Tumors: The Factors Affecting Secondary Recurrence and Survival After Recurrence.
Ege HV, Başaran D, Gültekin M … +35 more , Özgül N, Boran N, Koç S, Üstün Y, Çakır C, Yüksel D, Oktar O, Ege G, Tokalıoğlu AA, Şahin M, Uçar Y, Kılıç F, Aytekin O, Ersak B, Ünsal M, Tekin ÖM, Kılıç Ç, Koçak Ö, Öztürk Ç, Taşkın S, Ortaç F, Üreyen I, Toptaş T, Baş S, Narin MA, Taşçı T, Uçar G, Şendur MA, Civelek B, Uncu D, Erdoğan Ö, Sancı M, Yalçın HR, Selçuk İ, Turan T
J Cancer · 2026 · PMID 41869453 · Full text
INTRODUCTION: Adult-type granulosa cell tumors (AGCTs) are rare ovarian neoplasms with a low overall incidence of recurrence, and also data on secondary recurrence and survival after relapse remain limited. This study ai...
INTRODUCTION: Adult-type granulosa cell tumors (AGCTs) are rare ovarian neoplasms with a low overall incidence of recurrence, and also data on secondary recurrence and survival after relapse remain limited. This study aimed to identify factors associated with secondary recurrence and survival after recurrence in patients with recurrent AGCTs. METHODS: This multicenter retrospective study included 52 patients with recurrent AGCTs identified among 484 patients treated between 2000 and 2023. Clinical characteristics, treatment modalities, and outcomes were analyzed, with a particular focus on factors associated with secondary recurrence and survival after first recurrence. Recurrence-free survival and overall survival after first recurrence (OS-FR) were evaluated using Kaplan-Meier analysis. RESULTS: The mean follow-up duration was 99.2 ± 61.5 months. Secondary recurrence occurred in 17 patients (32.7%). A serum CA-125 level >35 U/mL at the time of first recurrence was significantly associated with an increased risk of secondary recurrence (p=0.01). Factors significantly associated with improved OS-FR included a CA-125 level ≤35 U/mL at initial diagnosis and at first recurrence, absence of residual disease following surgery for the first recurrence, and administration of salvage chemotherapy (all p<0.05). In subgroup analysis, salvage chemotherapy was associated with improved OS-FR in patients with residual disease or those who did not undergo surgery (p < 0.01), but not in patients who achieved complete cytoreduction (p = 0.67). CONCLUSIONS: Secondary recurrence remains a significant clinical challenge in AGCTs. Serum CA-125 levels, surgical outcomes at first recurrence, and the use of salvage chemotherapy may help management strategies in recurrent disease.
Impact of Skeletal Muscle-related Parameters on Survival in Patients with Advanced Pancreatic Cancer Treated with Gemcitabine plus Nab-paclitaxel as First-line Chemotherapy.
Matsuo N, Yamaguchi T, Yukami H … +7 more , Kodama H, Ikegami T, Kadono T, Kameisihi S, Okemoto D, Fakhrejahani E, Nishikawa H
J Cancer · 2026 · PMID 41869452 · Full text
BACKGROUND: Sarcopenia, defined as a reduction in muscle mass assessed using scales such as the psoas muscle mass index (PMI), is accompanied by decreased muscle strength or physical function. However, sarcopenia's effec...
BACKGROUND: Sarcopenia, defined as a reduction in muscle mass assessed using scales such as the psoas muscle mass index (PMI), is accompanied by decreased muscle strength or physical function. However, sarcopenia's effect in patients with pancreatic cancer (PC) receiving chemotherapy remains unclear. In addition, recent international studies have demonstrated that intramuscular fat infiltration, assessed using parameters such as FRPM, is associated with poor prognosis across various malignancies. However, evidence regarding its prognostic significance in pancreatic cancer remains limited. We aimed to evaluate the relationship between sarcopenia and the prognosis of patients with PC receiving palliative chemotherapy. METHODS: We retrospectively reviewed patients diagnosed with unresectable PC who received gemcitabine plus nab-paclitaxel (GnP) as the first-line therapy at our hospital between 2018 and 2021. We calculated PMI, defined as the sum of the bilateral psoas muscle mass at the lumbar three (L3) level and FRPM, defined as the sum of areas within the psoas muscles corresponding to fat at the L3 level from Vincent® on the CT images. We compared the overall survival (OS) between the PMI-high and PMI-low groups and the FRPM-high and FRPM-low groups. RESULTS: Of 46 patients, 37 were eligible. Eighteen (49%) and 19 (51 %) patients were classified into PMI-high and PMI-low groups, respectively. Twenty (54%) and 17 patients (46%) were classified into FRPM-high and FRPM-low groups, respectively. The median OS was 16.4 months in PMI-high and 8.7 months in PMI-low groups (hazard ratio [HR]: 0.45, 95% confidence interval [CI]: 0.23-0.90, P < 0.01). The median OS was 15.6 months in FRPM-low and 8.5 months in FRPM-high groups (HR: 0.36, 95% CI: 0.18-0.76, P < 0.01). In multivariate analysis, the presence of ascites (P < 0.01), PMI-low (P = 0.02), and FRPM-high (P = 0.03) were independent adverse prognostic factors for OS. CONCLUSION: Muscle-related parameters may be independent indicators of poor prognosis in patients with PC treated with first-line GnPs.
Mapping Myeloid Cell Diversity in Diffuse Large B-Cell Lymphoma: Impact on T Cell Exhaustion and Clinical Prognosis.
Wang J, Lv L, Li Z … +2 more , Yao X, Ding N
J Cancer · 2026 · PMID 41869451 · Full text
Diffuse large B-cell lymphoma (DLBCL) is an aggressive subtype of B-cell lymphoma characterized by genetic variability and clinical heterogeneity. Single-cell sequencing technology enables mapping of intra-tumoral hetero...
Diffuse large B-cell lymphoma (DLBCL) is an aggressive subtype of B-cell lymphoma characterized by genetic variability and clinical heterogeneity. Single-cell sequencing technology enables mapping of intra-tumoral heterogeneity and microenvironment interactions. In this study, we analyzed single-cell and RNA expression microarray data from over 3,000 DLBCL patients to investigate the immune landscape of the tumor microenvironment and its association with clinical prognosis. Malignant B cells identified through B-cell receptor (BCR) clonal analysis and copy number variation (CNV) assessment exhibited enrichment in pathways related to the cell cycle, DNA replication and p53 signaling, which were closely related to adverse survival outcomes. Next, the myeloid cells derived from DLBCL tumor tissues could be further clustered into several distinct types, primarily comprising dendritic cells and macrophages. The increased prevalence of macrophages within the tumor microenvironment was correlated with inferior overall survival. Additionally, CellChat analysis revealed that frequent interactions between macrophages and CD8 T cells may contribute to T cell exhaustion and create an immunosuppressive microenvironment. Collectively, the diverse sub-populations, particularly the immunosuppressive macrophages regulated immune suppression status within tumor microenvironment and represented a potential therapeutic target for DLBCL patients.
Clinical Outcomes and Individualized Seed Implantation Planning for Iodine-125 Seeds Brachytherapy in Lymph Node Metastases.
Huang D, Zhong Z, Zhang F … +1 more , Lin L
J Cancer · 2026 · PMID 41869450 · Full text
BACKGROUND: Lymph node metastasis (LNM) critically influences cancer prognosis and treatment. This study explored the efficacy and prognostic factors of CT-guided radioactive iodine-125 (¹²⁵I) seed brachytherapy (RISB) f...
BACKGROUND: Lymph node metastasis (LNM) critically influences cancer prognosis and treatment. This study explored the efficacy and prognostic factors of CT-guided radioactive iodine-125 (¹²⁵I) seed brachytherapy (RISB) for LNM and optimized the therapeutic dosage. METHODS: We conducted a single-center retrospective cohort study analyzing 81 cases with histologically confirmed LNM (≤ 5 cm) from diverse primary cancers treated with CT-guided RISB. Postoperative dosimetric parameters (D90, D100, V90, V100, V150, V200) were assessed. Treatment response was evaluated at 6 months using RECIST 1.1, calculating the objective response rate (ORR) and local control rate (LCR). Patients were categorized into objective response and non-objective response groups based on treatment efficacy, and factors influencing treatment efficacy were identified through logistic regression analysis. Based on the ROC curve, the Youden index method was used to determine the dose optimization cutoff value. RESULTS: The overall ORR was 71.6%, and LCR was 96.3%. The complication rate was 3.7%. Tumor size was an independent influencing factor for efficacy. Higher postoperative dosimetric parameters were associated with efficacy but were not independent influencing factors. ROC analysis identified the optimal D90 threshold as 102.7 Gy. The ORR in patients who achieved D90 > 102.7 Gy (n = 65, ORR = 81.54%) was significantly higher than in patients with D90 ≤ 102.7 Gy (n = 16, ORR = 31.25%) (p < 0.01). Complication rates did not differ between dose groups. CONCLUSION: Patients with LNM undergoing RISB can achieve a significantly higher ORR by ensuring a postoperative D90 > 102.7 Gy, without increasing the risk of complications. This dose threshold serves as a practical reference for clinical dose planning. Tumor size independently influences better response, guiding patient selection.
Potential influence of omentin-1 genetic variants on the clinicopathological features of patients with hepatocellular carcinoma.
Hu SL, Lee HL, Lien MY … +3 more , Wu ER, Yang SF, Tang CH
J Cancer · 2026 · PMID 41869449 · Full text
Hepatocellular carcinoma (HCC) ranks as the fifth supreme prevalent cancer within men globally and the ninth among female, serving as a significant contributor to cancer-associated deaths. The adipokine omentin-1 has bee...
Hepatocellular carcinoma (HCC) ranks as the fifth supreme prevalent cancer within men globally and the ninth among female, serving as a significant contributor to cancer-associated deaths. The adipokine omentin-1 has been demonstrated to have a defensive effect by decreasing the secretion of proinflammatory cytokines. The connections among lifestyle factors that promote cancer, polymorphisms, and HCC are still not well understood. Our investigation focused on the influence of clinicopathological characteristics and four variants of the gene (rs2274907, rs35779394, rs4656959, and rs79209815) on healthy controls as well as Taiwanese individuals with HCC. According to our data, individuals with the rs79209815 variant (TC or CC genotypes) are at an elevated risk of progressing to stage III/IV disease and larger tumors than those with the TT genotype. Males exhibited these associations more prominently than females. Moreover, expression levels were markedly reduced in individuals with the wild-type TT homozygous genotype when compared to those with the TC or CC genotypes of rs79209815. The complexity of genetic influences on HCC is highlighted by our study, which suggests that polymorphisms may have an impact on tumor stage and progression.
Integrative analysis of lysosome-dependent cell death related molecular subtypes and prognosis prediction in papillary thyroid carcinoma.
Xu Y, Wang Q, Zhang N … +2 more , He F, Mao X
J Cancer · 2026 · PMID 41869448 · Full text
BACKGROUND: Papillary thyroid carcinoma (PTC), the most common thyroid malignancy, shows marked clinical heterogeneity despite generally favorable outcomes. Lysosome-dependent cell death (LDCD), a form of programmed deat...
BACKGROUND: Papillary thyroid carcinoma (PTC), the most common thyroid malignancy, shows marked clinical heterogeneity despite generally favorable outcomes. Lysosome-dependent cell death (LDCD), a form of programmed death triggered by lysosomal membrane permeabilization, has emerged as a potential cancer therapy target, but its role in PTC remains unclear. METHODS: Transcriptomic data from public cohorts were analyzed to identify LDCD-related genes (LDCDRG) associated with PTC prognosis. Cox analysis and LASSO regression analyses were performed to construct a prognostic model. Immune landscape, drug sensitivity, and single-cell expression profiles were examined. Functional experiments were conducted to verify the biological effects of the key gene on PTC cell proliferation, viability, and invasion. RESULTS: Nineteen LDCDRG were differentially expressed between normal and tumor tissues, defining three molecular subtypes with distinct immune and prognostic profiles. A six-LDCDRG signature (, , , , and ) effectively stratified patients into high- and low-risk groups with significantly different survival outcomes and acceptable predictive performance. High-risk patients showed reduced immune infiltration and lower predicted immunotherapy-related immune activity. LMTK3, the highest-risk gene, was highly expressed in PTC cells, and its knockdown suppressed proliferation and invasion CONCLUSIONS: The established six-LDCDRG signature provides an exploratory tool for risk stratification and survival prediction, while emerges as potential target worthy of further investigation. These findings deepen our understanding of lysosome-dependent cell death in thyroid carcinogenesis and may provide insights into the development of personalized management strategies and novel treatment approaches for high-risk PTC patients.
Molecular Mechanisms of Symptom Fluctuations in Malignant Tumor Patients: Stable by Day and Severe at Night.
Xie Z, Jin W, Pang J … +2 more , Hu K, Li L
J Cancer · 2026 · PMID 41869447 · Full text
Patients with malignant tumors often experience fluctuations in the severity of their symptoms depending on the time of day. In traditional Chinese medicine, symptoms are said to follow a pattern of "mild in the morning,...
Patients with malignant tumors often experience fluctuations in the severity of their symptoms depending on the time of day. In traditional Chinese medicine, symptoms are said to follow a pattern of "mild in the morning, stable by day, worsening in the evening, and severe at night." This article investigates the circadian chronobiology of symptoms and examines their molecular pathophysiology. Evidence suggests that disruptions in core circadian clock genes, such as BMAL1 and PER, along with the dysregulation of cellular metabolic pathways, immune responses, and endocrine functions, synergistically facilitate tumor growth and metastasis during nocturnal periods. These molecular alterations contribute to symptom exacerbation through mechanisms which include direct tumor invasion, neural infiltration, inflammatory processes, dorsal root ganglion (DRG) sensitization, and abnormal melatonin secretion. The article further explores three chronotherapeutic strategies and assesses melatonin's role in targeted oncological therapy, aiming to optimize circadian regulation and symptom management, thereby providing a scientific foundation for personalized anti-tumor interventions that are based on circadian rhythms.
RNF216 as a Promising Biomarker for Prognosis, Immunotherapy, and Chemotherapy in LIHC: A Comprehensive Pan-Cancer Analysis and Experimental Validation.
Du K, Liang X, Qin B … +7 more , Liu Z, Liu N, Li P, Wang Q, Qi Y, Shi E, Li K
J Cancer · 2026 · PMID 41869446 · Full text
BACKGROUND: RNF216 belongs to the E3 ubiquitin ligase family and plays a role in the development of various diseases. However, its systematic role in pan-cancer development has not been systematically explored. METHODS:...
BACKGROUND: RNF216 belongs to the E3 ubiquitin ligase family and plays a role in the development of various diseases. However, its systematic role in pan-cancer development has not been systematically explored. METHODS: Publicly available data from The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO), and the Human Protein Atlas (HPA) were utilized. The analysis was conducted using R software and online platforms such as STRING, TISIDB, and TISCH to evaluate the role of RNF216. CCK-8 and other experiments have confirmed the function of RNF216 in liver hepatocellular carcinoma (LIHC). RESULTS: RNF216 was significantly elevated in most tumor tissues relative to adjacent normal tissues; meanwhile, the mutation rate of RNF216 in LIHC tissues was also significantly elevated relative to normal tissues. The expression levels of RNF216 vary in tumor mutational burden (TMB) and microsatellite instability (MSI) across different tumors. It demonstrated significant diagnostic and prognostic value and was associated with clinicopathologic features in multiple cancers, especially in LIHC. The protein-protein interaction (PPI) network and GSCALite suggested that RNF216 and its co-expressed genes may promote tumor growth by regulating mitosis, cell death, and DNA damage. Gene Set Enrichment Analysis (GSEA) further revealed a positive correlation between RNF216 and cell cycle regulation pathways. RNF216 is significantly related to immune cell infiltration and expressed in various types of immune cells. Knockout of RNF216 mediated by siRNA inhibits cell proliferation and reduces the migration and invasion capability of HepG2 and Hep3B cells. CONCLUSION: RNF216 is strongly upregulated in various tumors, including LIHC, and plays an extremely important role in tumor diagnosis and prognosis. Targeted knockout of RNF216 is beneficial for improving the efficacy of immunotherapy and chemotherapy.
Spatial Omics in Gastrointestinal Oncology: Recent Advances, Therapeutic Insights, and Clinical Translation.
Zhong L, Li Q, Xiong T … +6 more , Lin S, Wang K, Li G, Yan Y, Liu J, Xue C
J Cancer · 2026 · PMID 41869445 · Full text
Gastrointestinal (GI) cancers remain a leading cause of cancer-related morbidity and mortality worldwide, largely due to their molecular heterogeneity, complex tumor microenvironment (TME), and variable treatment respons...
Gastrointestinal (GI) cancers remain a leading cause of cancer-related morbidity and mortality worldwide, largely due to their molecular heterogeneity, complex tumor microenvironment (TME), and variable treatment responses. In recent years, the emergence of spatially resolved omics technologies-encompassing spatial transcriptomics, proteomics, metabolomics, and epigenomics-has revolutionized the ability to interrogate tumor architecture with unprecedented resolution. These methods enable precise mapping of cellular and molecular interactions within intact tissue contexts, thereby uncovering spatially defined niches that influence tumor progression, immune evasion, and therapeutic resistance. In GI malignancies such as colorectal, gastric, and esophageal cancers, spatial omics have provided critical insights into cancer-stromal-immune crosstalk, identified predictive biomarkers for immunotherapy and targeted agents, and guided the development of novel therapeutic strategies. This review synthesizes the latest advances in spatial omics applied to GI oncology over the past five years, with an emphasis on their integration into early diagnosis, treatment stratification, and real-time monitoring of therapeutic efficacy. We also discuss current challenges, including standardization, data integration, and clinical validation, as well as future directions for incorporating spatial profiling into routine oncology practice. By bridging the gap between bench discoveries and bedside applications, spatial omics hold transformative potential for achieving truly personalized treatment in gastrointestinal cancers.
C4orf3 Regulates HIF-1α Degradation Under Hypoxic Conditions and Contributes to the Malignant Phenotype in Small Cell Lung Cancer.
Sakanashi K, Onishi H, Iwamoto N … +11 more , Nakanishi Y, Itoyama S, Masuda S, Ozono K, Yanai K, Nakamura K, Nagami M, Nishiyama K, Kojima M, Oda Y, Nakamura M
J Cancer · 2026 · PMID 41869444 · Full text
Hypoxia is a critical feature of the tumour microenvironment in small cell lung cancer (SCLC) and contributes to malignant progression through hypoxia-inducible factor 1 alpha (HIF-1α)-mediated transcriptional programs....
Hypoxia is a critical feature of the tumour microenvironment in small cell lung cancer (SCLC) and contributes to malignant progression through hypoxia-inducible factor 1 alpha (HIF-1α)-mediated transcriptional programs. However, the upstream regulators that maintain HIF-1α stability under hypoxic conditions remain incompletely understood. In this study, we identified the chromosome 4 open reading frame 3 (C4orf3) as a hypoxia-inducible gene and investigated its functional significance in SCLC. C4orf3 expression is upregulated under hypoxic conditions, and its knockdown suppresses cell proliferation, migration, and invasion and reduces tumour growth . Mechanistically, C4orf3 depletion decreased HIF-1α protein levels even under chemically induced hypoxia, suggesting that its regulation is independent of the canonical PHD-VHL degradation pathway. Further analysis demonstrated that C4orf3 modulates HIF-1α stability through PIASy-mediated SUMOylation. Clinical relevance was supported by a positive association between C4orf3 and HIF-1α expression in resected SCLC tissues. These findings suggested that C4orf3 functions as a regulator of hypoxic adaptation in SCLC by maintaining HIF-1α stability and may represent a potential therapeutic target in hypoxia-driven tumour progression.
FAM188B promotes progression of hepatocellular carcinoma by regulating YAP/TAZ via interaction with USP10.
Hu S, Wen Y, Chen Y … +9 more , Fang Y, Mu M, Tu L, Chen W, Tu K, Liu X, Xu Q, Huang D, Li X
J Cancer · 2026 · PMID 41869443 · Full text
BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide and its incidence and mortality rates remain high. Therefore, new diagnostic and therapeutic approaches are urgently required. F...
BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide and its incidence and mortality rates remain high. Therefore, new diagnostic and therapeutic approaches are urgently required. Family with sequence similarity 188 member B (FAM188B) encodes an evolutionarily conserved protein that is highly expressed in various cancers. While FAM188B has been implicated in the progression of several tumors, its role in HCC progression remains unknown. METHODS: We analyzed FAM188B expression in HCC using The Cancer Genome Atlas (TCGA) and The University of Alabama at Birmingham Cancer data analysis Portal (UALCAN) databases. Functional studies included proliferation, migration, and invasion assays, as well as xenograft models. Co-immunoprecipitation (Co-IP), Western blotting, and immunofluorescence were used to investigate the FAM188B-Ubiquitin-specific peptidase 10 (USP10)-Yes-associated protein/Transcriptional coactivator with PDZ-binding motif (YAP/TAZ) interaction. RESULTS: FAM188B was found highly expressed in HCC cells and associated with poor prognosis. Both and , FAM188B promoted the proliferation, migration, and invasion of HCC. FAM188B directly interacts with and stabilizes USP10 and the downregulation of FAM188B by shRNA led to decreased USP10 and YAP/TAZ protein levels, suggesting that FAM188B may regulate the YAP/TAZ pathway through its interaction with USP10. CONCLUSION: Our findings reveal that FAM188B plays a crucial role in enhancing HCC cell proliferation, migration, and invasion, primarily through regulating the USP10/YAP/TAZ signaling axis, which was validated and .
MZB1 at the ER-immunity interface: from antibody folding to disease vulnerability in autoimmunity, inflammation, and cancer.
Zhang Y, Yang W, Yang X … +5 more , Pan Y, Guo R, Chen D, Tang S, Zhang X
J Cancer · 2026 · PMID 41869442 · Full text
MZB1 (marginal zone B and B1 cell-specific protein 1) is an endoplasmic reticulum-resident molecular chaperone that is predominantly expressed in marginal zone B cells, B1 cells, plasma cells, and pDCs. Functioning as a...
MZB1 (marginal zone B and B1 cell-specific protein 1) is an endoplasmic reticulum-resident molecular chaperone that is predominantly expressed in marginal zone B cells, B1 cells, plasma cells, and pDCs. Functioning as a co-chaperone of GRP94 and BiP, MZB1 selectively facilitates the proper folding and secretion of immunoglobulin M (IgM) and J-chain-containing immunoglobulin A (IgA) dimers, and maintains the homeostasis of highly secretory cells by upregulating the expression of partner proteins such as BiP/GRP94. This review highlights the emerging role of MZB1 across various pathological conditions. In autoimmune diseases such as systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA), MZB1 contributes to aberrant autoantibody and cytokine secretion. MZB1 also modulates inflammatory responses in conditions such as colitis and periodontitis by regulating the B cell-skewed inflammatory microenvironment. In oncology, MZB1 is overexpressed in breast cancer (BC), lymphoma, and multiple myeloma (MM), where it is associated with enhanced tumor cell proliferation and poor prognosis. Conversely, in hepatocellular carcinoma (HCC) and gastric cancer (GC), MZB1 is transcriptionally silenced due to promoter hypermethylation. In summary, the tissue-specific expression pattern of MZB1 endows it with potential as both a diagnostic biomarker and therapeutic target, holding significant implications for the exploration of future cancer prognosis and treatment strategies.
A Comprehensive Review of Nanotechnological Innovations in Cancer: from Molecular Pathways to Clinical Applications.
Nawaz S, Ho W, Nawaz A … +7 more , Rahman SU, Zahid A, Alzahrani KJ, Halawani IF, Alzahrani FM, Chen CC, Qadeer A
J Cancer · 2026 · PMID 41869441 · Full text
This review offers an inclusive overview of current cancer treatment options. It examines emerging trends in molecular mechanisms, therapeutic challenges, and nanotechnological innovations that may significantly improve...
This review offers an inclusive overview of current cancer treatment options. It examines emerging trends in molecular mechanisms, therapeutic challenges, and nanotechnological innovations that may significantly improve patient outcomes. Cancer is a complex disease characterized by unregulated cellular proliferation, invasion of adjacent tissues, and metastasis. It remains a leading cause of death worldwide, with increasing incidence attributed to factors such as an aging demographic, lifestyle habits, and environmental stimuli. This review examines various cancer types, their associated risk factors, and critical molecular pathways, with the PI3K/Akt/mTOR and Wnt/β-catenin pathways, that facilitate cancer progression. The intricate process of metastasis, the leading cause of cancer fatalities, is examined in depth. The discussion encompasses a comprehensive analysis of diagnostic methods and conventional treatment modalities, including surgical intervention, radiation therapy, chemotherapy, and targeted therapies, and addresses their limitations, including toxicity, drug resistance, and unintended side effects. The advent of nanoparticle-based platforms in cancer therapy has facilitated significant progress in targeted drug delivery, enhanced imaging for prompt diagnosis, and the advancement of treatments, such as photothermal and photodynamic therapies. Nanoparticles may provide a vital function in overcoming drug resistance, thereby improving treatment effectiveness. Furthermore, this review emphasizes cancer prevention strategies, which include lifestyle changes and vaccination efforts. The oncological treatment landscape is poised for transformation through advancements in precision medicine, gene therapy, and artificial intelligence. Incorporating nanotechnology into these emerging strategies holds substantial potential for developing more personalized and effective cancer therapies with reduced adverse effects.
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