Chahine S, Diab T, El Tannir M
… +3 more, Farhat G, Jurdi N, I Assi H
J Cancer Res Clin Oncol
· 2026 Jul · PMID 42402094
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BACKGROUND: Perivascular epithelioid cell tumors (PEComas) are rare mesenchymal neoplasms composed of epithelioid cells that co-express melanocytic and smooth muscle markers. They can arise in various anatomic sites, mos...BACKGROUND: Perivascular epithelioid cell tumors (PEComas) are rare mesenchymal neoplasms composed of epithelioid cells that co-express melanocytic and smooth muscle markers. They can arise in various anatomic sites, most commonly the uterus, retroperitoneum, gastrointestinal tract, and liver. While most PEComas are sporadic and associated with TSC1/TSC2 mutations leading to mTOR pathway activation, a distinct molecular subset harbors TFE3 gene rearrangements, often exhibiting more aggressive clinical behavior. Given their rarity, the diagnosis and management of PEComas remain challenging and largely unstandardized. CASE PRESENTATION: We report the case of a 37-year-old woman with no significant medical history who presented with fatigue, unintentional weight loss, and vomiting. Imaging revealed a large hepatic mass and pulmonary nodules. Histopathological and immunohistochemical evaluation confirmed a diagnosis of TFE3-rearranged PEComa involving the liver and left upper lung lobe. The patient underwent right partial hepatectomy with complete resection of the hepatic lesion. Subsequent disease progression was noted in the lung, lymph nodes, and bone despite treatment with an mTOR inhibitor. CONCLUSION: TFE3-rearranged PEComas represent a rare and aggressive molecular subset with limited therapeutic options. This case demonstrates resistance to mTOR inhibition, highlighting the critical importance of molecular subtyping to distinguish TFE3-rearranged from TSC1/TSC2-mutant disease and guide individualized management. Expanded molecular profiling is essential to refine treatment strategies for this uncommon entity.
Wu Q, Yang L, Bai B
… +4 more, Jiang J, Liu T, Sun Y, Wang C
J Cancer Res Clin Oncol
· 2026 Jul · PMID 42387192
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BACKGROUND: Polypeptide N-acetylgalactosaminyltransferase 5 (GALNT5), a member of the GALNT enzyme family, has been implicated in the pathogenesis of various malignancies. However, its precise role in colorectal cancer (...BACKGROUND: Polypeptide N-acetylgalactosaminyltransferase 5 (GALNT5), a member of the GALNT enzyme family, has been implicated in the pathogenesis of various malignancies. However, its precise role in colorectal cancer (CRC) progression and its contribution to acquired resistance to the FOLFOX components (oxaliplatin and 5-fluorouracil) remains poorly understood. This study aimed to elucidate the biological functions of GALNT5 in CRC pathogenesis and chemoresistance. METHODS: GALNT5 expression in CRC cell lines was evaluated through integrated bioinformatics analyses, RNA sequencing (RNA-Seq), RT-qPCR, and Western blotting. Isogenic CRC sublines resistant to oxaliplatin (LoVo/L) or 5-fluorouracil (LoVo/5FU) were established separately by chronic exposure to each drug. RNA-Seq was employed to identify downstream signaling pathways and effector genes modulated by GALNT5. VVL lectin pull-down assays were performed to confirm that GALNT5 mediates O-GalNAc glycosylation of EGFR-an upstream activator of the PI3K/Akt signaling pathway. Functional assays, including CCK-8 and Transwell, were conducted to assess cell proliferation, apoptosis, and invasion. The involvement of the PI3K pathway was examined using the PI3K agonist 740Y-P, while expression changes of the downstream effector ABCC1 were analyzed both in vitro and in vivo. RESULTS: GALNT5 was significantly upregulated in CRC cell lines compared to the normal colonic epithelial cell line NCM460. Knockdown of GALNT5 markedly suppressed proliferation and invasion, while promoting apoptosis in both parental and chemoresistant CRC cells. Silencing GALNT5 enhanced the sensitivity of resistant cells to oxaliplatin (L-OHP) and 5-fluorouracil (5FU), an effect that was reversible upon PI3K pathway activation, indicating the involvement of the PI3K/Akt axis. Mechanistically, GALNT5 activated the PI3K/Akt axis through O-GalNAc glycosylation of EGFR. Furthermore, GALNT5 depletion led to downregulation of the multidrug resistance-associated protein ABCC1 in vitro and in vivo. CONCLUSION: GALNT5 facilitates malignant progression in CRC by promoting O-GalNAc glycosylation of EGFR and thereby activating the PI3K/Akt pathway, and confers resistance to L-OHP and 5FU through upregulation of ABCC1. These findings suggest GALNT5 as a potential diagnostic biomarker and a promising therapeutic target for overcoming chemoresistance in CRC.
Baruah TJ, Bora J, Mishra R
… +11 more, Dutta S, Borah AK, Baishya J, Singh C, Barman I, Thapliyal S, Malik S, Preetam S, Kumar D, Choudhary N, Kondaveeti SB
J Cancer Res Clin Oncol
· 2026 Jun · PMID 42380680
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Early detection of cancer remains a major challenge in oncology. Circulating tumour markers (CTMs), including circulating tumour cells, circulating tumour DNA, exosomes, microRNAs, and tumour-associated proteins, offer a...Early detection of cancer remains a major challenge in oncology. Circulating tumour markers (CTMs), including circulating tumour cells, circulating tumour DNA, exosomes, microRNAs, and tumour-associated proteins, offer a minimally invasive strategy for monitoring tumour dynamics through liquid biopsy. However, their clinical translation is limited by low abundance, heterogeneity, and instability in body fluids. Recent advances in nanotechnology have enabled the development of highly sensitive and specific nano-biosensors that address many of these barriers. This review highlights the current progress in CTM detection using electrochemical, optical, plasmonic, and microfluidic-integrated platforms. Advanced nanomaterials such as graphene, carbon nanotubes, noble metal nanoparticles, quantum dots, and nanozymes are discussed for their roles in signal amplification, surface functionalization, and biomarker selectivity. Special focus is placed on lab-on-a-chip and wearable biosensors for multi-marker, point-of-care testing. To amplify the signals associated with nanobiosensors, various technologies, such as surface functionalization, aptamer and antibody functionalization, and nanozymes, have been integrated with the nanobiosensors.
Zhou W, Song M, Song J
… +4 more, You L, Zhu Y, Chen H, Zhou J
J Cancer Res Clin Oncol
· 2026 Jun · PMID 42366272
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BACKGROUND: Postoperative recurrence and metastasis constitute critical obstacles for resected non-small cell lung cancer (NSCLC) patients, and reliable predictive biomarkers are still scarce. This study aimed to evaluat...BACKGROUND: Postoperative recurrence and metastasis constitute critical obstacles for resected non-small cell lung cancer (NSCLC) patients, and reliable predictive biomarkers are still scarce. This study aimed to evaluate whether folate receptor-positive CTC (FRCTC) predicts postoperative progressive disease (PD) in stage I-IIIA NSCLC and to explore noninvasive biomarkers for high-risk patients. METHOD: We retrospectively enrolled stage I-IIIA NSCLC patients undergoing radical resection from 2018 to 2021. Perioperative blood samples were collected for FRCTC detection. PD-related risk factors were analyzed to establish a postoperative prognostic model. RESULT: In total, 171 NSCLC patients were enrolled. Stage III disease had higher preoperative FR⁺CTC positivity than stage I-II (69.39% vs. 52.46%, P = 0.043). Male gender, smoke, squamous histology and stage III correlated with elevated postoperative FR⁺CTC positivity (all P < 0.05). Among 152 patients for survival analysis, 36 developed 36‑month PD. Multivariate Cox confirmed postoperative FR⁺CTC positivity (HR = 2.25, P = 0.018) and stage III (HR = 3.43, P = 0.005) as independent PD predictors. FR⁺CTC conversion from preoperative negative to postoperative positive conferred the highest PD risk and shortened PFS. CONCLUSION: Postoperative FRCTC positive and TNM stage III were independent risk factors for 36 months PD in NSCLC patients after radical resection. Postoperative FR⁺CTC positivity correlated with shortened PFS and effectively predicted postoperative PD. Conversion from preoperative FR⁺CTC negativity to postoperative positivity conferred the highest progression risk. Perioperative FR⁺CTC detection and dynamic monitoring are promising liquid biopsy biomarkers for postoperative progression prediction.
Chen R, Zha H, Zhu Q
… +5 more, Liu X, Huang L, Li C, Wang J, Zha X
J Cancer Res Clin Oncol
· 2026 Jun · PMID 42365133
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BACKGROUND: Accurate assessment of axillary lymph node status after neoadjuvant systemic therapy (NST) is essential for de-escalating surgery in node-positive breast cancer. Although various axillary surgeries based on s...BACKGROUND: Accurate assessment of axillary lymph node status after neoadjuvant systemic therapy (NST) is essential for de-escalating surgery in node-positive breast cancer. Although various axillary surgeries based on sentinel lymph node biopsy (SLNB) are widely reported, they still have limitations in this setting. Since metastatic lymph nodes inherently encompass sentinel nodes, we hypothesized that directly marking and retrieving these nodes could enable reliable restaging without SLNB. MATERIALS AND METHODS: In this single-arm, prospective cohort study, patients with pathologically confirmed axillary metastasis underwent ultrasound-guided injection of carbon nanoparticle suspension into the most suspicious lymph node(s) before NST. After completing NST, stained region lymph node biopsy (SrLNB) was performed to retrieve the marked nodes, followed by completion axillary lymph node dissection (ALND), without performing SLNB. The detection rate and false-negative rate (FNR) of SrLNB were evaluated to determine its feasibility. RESULTS: Between September 2020 and December 2022, 159 patients were included. The axillary pathological complete response (pCR) rate was 40.9% (65/159). SrLNB achieved a detection rate of 100% (159/159) and an overall FNR of 5.3% (5/94). The FNR remained within the 10% safety threshold across all patient subgroups. CONCLUSION: SrLNB is a feasible, economical, and straightforward technique for assessing axillary response after NST. With its high detection rate and acceptable FNR, SrLNB represents an alternative SLNB-independent strategy for axillary restaging in patients with initially node-positive breast cancer.
Doraczynska-Kowalik A, Matkowski R, Michalowska D
… +12 more, Chrusciel A, Semeniuk M, Blomka D, Lawicka P, Czykalko E, Abrahamowska M, Pietron A, Janus-Szymanska G, Pawlak I, Maciejczyk A, Szelachowska J, Laczmanska I
J Cancer Res Clin Oncol
· 2026 Jun · PMID 42334620
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PURPOSE: BRCA1 and BRCA2 are key susceptibility genes in hereditary breast and ovarian cancer (HBOC), with mutational status guiding PARP inhibitor therapy. While single-nucleotide variants (SNVs) predominate, the preval...PURPOSE: BRCA1 and BRCA2 are key susceptibility genes in hereditary breast and ovarian cancer (HBOC), with mutational status guiding PARP inhibitor therapy. While single-nucleotide variants (SNVs) predominate, the prevalence of copy number variants (CNVs) varies significantly across different populations. This study aims to determine the incidence of BRCA1/2 CNVs in the Polish population, where data remain scarce due to non-mandatory CNV testing. METHODS: We retrospectively analysed the results of genetic tests assessing the presence of BRCA1/2 CNVs performed in 2720 individuals tested at the Lower Silesian Oncology Centre (2021-2024), including 2702 breast/ovarian cancer patients and 18 unaffected relatives. The mean age was 54.7 ± 15.15 years. Genetic testing involved DNA extraction, NGS, and MLPA for CNV confirmation. Variants were classified according to ACMG-AMP guidelines and verified through independent testing. RESULTS: In this study, no BRCA2 CNVs were identified, consistent with previous Central European findings. Pathogenic BRCA1 CNVs were detected in 0.85% of the analyzed cohort and in 0.52% of the cancer patient subgroup, affecting 23 individuals from 13 families. Eight distinct BRCA1 CNVs were detected, the most common being exon 21 deletion. Affected families exhibited a high incidence of HBOC-related cancers, with early-onset breast cancer and a notable proportion of triple-negative breast cancer cases. CONCLUSIONS: This study highlights the clinical significance of BRCA1 CNVs in Polish patients with HBOC-spectrum cancers and their families. Although rare, these variants were associated with aggressive cancer phenotypes and early onset. Given their diagnostic and therapeutic implications, BRCA1 CNVs should be routinely analysed in high-risk families to ensure accurate detection and personalised treatment planning.
Amann N, Krückel A, Brückner L
… +9 more, Gocke J, Müller C, Heindl F, Hack CC, Stumpf K, Emons J, Fasching PA, Beckmann MW, Hörner M
J Cancer Res Clin Oncol
· 2026 Jun · PMID 42323771
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PURPOSE: Ovarian cancer is frequently associated with gBRCA1/2 mutations, which also confer a high lifetime risk of breast cancer in non-affected patients. While risk-reducing salpingo-oophorectomy (RRSO) is established...PURPOSE: Ovarian cancer is frequently associated with gBRCA1/2 mutations, which also confer a high lifetime risk of breast cancer in non-affected patients. While risk-reducing salpingo-oophorectomy (RRSO) is established in hereditary breast and ovarian cancer prevention, the recommendation for risk-reducing bilateral mastectomy (RRBM) remains unclear in gBRCA1/2mutovarian cancer patients due to high recurrence rates and limited survival. This study evaluates the preventive strategies of these patients in a real-world setting. METHODS: This retrospective study included 49 patients with gBRCA1/2mut HGSC treated at the Hereditary Breast and Ovarian Cancer Centre, University Hospital Erlangen, between 2012 and 2024. Clinical, pathological, treatment-related, and genetic data were collected and analyzed from electronic records. RESULTS: Among 49 patients with gBRCAmut HGSC, 44 out of 49 did not undergo a RRBM during follow-up. Intensified breast cancer surveillance was recommended to 33 patients. Although 19 out of 49 patients were formally recommended a RRBM, only two proceeded with the preventive option. Three additional patients chose the surgery driven by the diagnosis of metachronous breast cancer. 80% of the operations occurred > 60 months after ovarian cancer diagnosis. CONCLUSIONS: In patients with gBRCA1/2mut and a history of HGSC, RRBM is rarely chosen. Most patients prefer an intensified surveillance program. Due to low metachronous breast cancer rate in follow up care, RRBM seems to be an option just for long-term survivors. Individual patient preferences play a crucial role in the management strategy.
J Cancer Res Clin Oncol
· 2026 Jun · PMID 42319496
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OBJECTIVE: Thyroid cancer (TC) is the most common malignant tumor of the endocrine system, and its incidence has increased annually. Although TC generally has a favorable prognosis, some patients experience recurrence af...OBJECTIVE: Thyroid cancer (TC) is the most common malignant tumor of the endocrine system, and its incidence has increased annually. Although TC generally has a favorable prognosis, some patients experience recurrence after treatment. Therefore, understanding the pathogenic mechanisms of TC is crucial for improving its treatment. It was hypothesized that ITGA7 suppresses TC by binding to FN1 and inhibiting the PI3K/AKT pathway. This study aimed to test this hypothesis and elucidate the underlying mechanism. METHODS: Expression of Integrin Subunit Alpha 7 (ITGA7) and Fibronectin 1 (FN1) was evaluated in paired samples of normal thyroid and TC tissues via reverse transcription quantitative real-time PCR (RT-qPCR) and immunohistochemistry (IHC). ITGA7 and FN1 mRNA and protein levels were further assessed using RT-qPCR and Western blot analysis. Functional assays included Cell Counting Kit-8 for cell viability, 5-Ethynyl-2'-deoxyuridine (EdU) incorporation for proliferation, Transwell for migration and invasion, and flow cytometry for apoptosis. Protein interaction and co-localization between ITGA7 and FN1 were confirmed through co-immunoprecipitation and immunofluorescence (IF). Western blot was used to examine Phosphatidylinositol 3-kinase/Protein Kinase B (PI3K/AKT) signaling pathway components, and IHC was applied to assess related protein expression in clinical specimens. A xenograft model in nude mice was established to investigate the role of ITGA7 in tumor growth in vivo. Bioinformatics tools including STRING and GEPIA were utilized to predict potential interactions involving ITGA7. RESULTS: RT-qPCR and IHC revealed decreased ITGA7 expression in TC compared to adjacent normal tissues. Consistent downregulation was observed at both mRNA and protein levels in TC cell lines. Functional loss-of-function experiments showed that ITGA7 knockdown enhanced viability, proliferation, migration, and invasion, and suppressed apoptosis. FN1 was identified as an ITGA7-binding partner with negatively correlated expression. FN1 was upregulated in TC tissues, and its silencing impeded malignant phenotypes including proliferation and migration, while promoting apoptosis. The protein interaction and co-localization between ITGA7 and FN1 were experimentally validated. Western blot analysis demonstrated that silencing ITGA7 upregulated FN1 and activated the PI3K/AKT pathway. Conversely, FN1 knockdown suppressed pathway activity. In vivo studies confirmed that ITGA7 suppressed tumor progression by inhibiting the FN1-mediated activation of the PI3K/AKT pathway. Rescue assays demonstrated that FN1 depletion counteracted the oncogenic effects of ITGA7 silencing. CONCLUSION: The expression of ITGA7 in TC tissues and cells was significantly lower than that in normal tissues and cells. ITGA7 inhibits TC progression by interacting with FN1 and suppressing PI3K/AKT signaling pathway activation.
Yan A, Zhu L, Luo B
… +5 more, Pang X, Qin J, Dong L, Zhao Y, Chen N
J Cancer Res Clin Oncol
· 2026 Jun · PMID 42313263
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Osteosarcoma (OS) represents one of the most prevalent primary malignant bone tumors affecting children and adolescents. Despite the establishment of standard treatment protocols (surgery and chemotherapy) in the 1980s,...Osteosarcoma (OS) represents one of the most prevalent primary malignant bone tumors affecting children and adolescents. Despite the establishment of standard treatment protocols (surgery and chemotherapy) in the 1980s, patient survival rates remain suboptimal. This underscores the critical need for the development and investigation of novel therapeutic technologies. Neutron capture therapy (NCT), an emerging precision therapeutic modality, selectively targets and eradicates tumor cells while minimizing damage to surrounding healthy tissues. In this study, we developed a novel agent, Gd-DOTA-BMTP, by attaching the cyclic nonapeptide c(CGRRAGGSC) to DOTA, followed by chelation of gadolinium (Gd) to the DOTA-BMTP. This peptide can specifically targeting osteosarcoma and binding to IL-11Rα, a cell surface receptor. Gd-DOTA-BMTP demonstrated excellent targeting specificity and a favorable biosafety profile. Furthermore, rigorous in vitro and in vivo evaluations confirmed the efficacy of Gd-DOTA-BMTP in suppressing osteosarcoma, specifically by enhancing radiosensitivity to neutron irradiation. Collectively, these findings suggest that Gd-DOTA-BMTP holds potential as a candidate for Gadolinium Neutron Capture Therapy (Gd-NCT) of osteosarcoma.
J Cancer Res Clin Oncol
· 2026 Jun · PMID 42307776
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PURPOSE: To compare the clinicopathologic characteristics, dissemination patterns, and survival outcomes of uterine carcinosarcoma (CS) and grade 3 endometrioid adenocarcinoma (G3EAC), focusing on nodal distribution and...PURPOSE: To compare the clinicopathologic characteristics, dissemination patterns, and survival outcomes of uterine carcinosarcoma (CS) and grade 3 endometrioid adenocarcinoma (G3EAC), focusing on nodal distribution and the impact of complete surgical staging. METHODS: This retrospective cohort study included 105 patients (43 CS, 62 G3EAC) who underwent primary surgical treatment at a single tertiary center between 2000 and 2016. A focused analysis was performed on a high-quality subgroup of 80 patients (76.2%) who underwent systematic pelvic and para-aortic lymphadenectomy. Progression-free survival (PFS) and overall survival (OS) were estimated using Kaplan-Meier methods, and independent prognostic factors were evaluated via Cox proportional hazards regression models. RESULTS: CS patients were significantly older than G3EAC patients (p = 0.005). While CS showed lower rates of deep myometrial invasion (44.2% vs. 67.7%; p = 0.016), it was associated with significantly higher positive peritoneal cytology (30.8% vs. 7.0%; p = 0.002). Overall lymph node metastasis rates were comparable between the groups (35.9% vs. 24.6%; p = 0.230). CS was associated with a significantly lower 5-year PFS (35.6% vs. 63.4%; p = 0.042), particularly in Stage IA disease (median PFS 7.7 months), and a trend toward lower 5-year OS (41.1% vs. 64.0%; p = 0.088). Multivariable analysis identified advanced age as the sole independent predictor of poor prognosis (OS HR 1.043, p = 0.021; PFS HR 1.039, p = 0.032). Notably, combined chemoradiotherapy (CRT) effectively eliminated the survival gap between histologies (5-year OS: 72.7% for CS vs. 70.0% for G3EAC; p = 0.590). CONCLUSION: Uterine carcinosarcoma exhibits minimal local invasion but high systemic aggressiveness. Traditional markers of local spread, such as myometrial invasion, are less predictive for CS. Systematic surgical staging remains essential, and multimodal adjuvant CRT is crucial to mitigating the inherent survival disadvantage of CS.
Lunger L, Schwoy M, Dinkel A
… +5 more, Meissner VH, Schiele S, Jahnen M, Gschwend JE, Herkommer K
J Cancer Res Clin Oncol
· 2026 Jun · PMID 42289014
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BACKGROUND: Loneliness in cancer survivors is associated with a variety of negative consequences to physical and mental health. Research regarding the impact of loneliness on health-related quality of life and mental hea...BACKGROUND: Loneliness in cancer survivors is associated with a variety of negative consequences to physical and mental health. Research regarding the impact of loneliness on health-related quality of life and mental health outcomes in prostate cancer (PC) survivors is scarce. The current study aimed to investigate prevalence and determinants of loneliness in long-term PC survivors following radical prostatectomy (RP). METHODS: A total of 3127 PC survivors (mean age 79.5 years, SD 6.4) from the multicenter German Familial PC Database returned the study questionnaires during the COVID-19 pandemic, after an average of 17.4 years (SD = 3.8) following RP. Loneliness was assessed using a single item measure. Validated self-reporting questionnaires were used to assess anxiety and depressive symptoms, health related quality of life, and frailty. Descriptive statistics, chi-square tests, and logistic regression analysis were conducted to examine the prevalence, correlates, and determinants of loneliness in PC patients. RESULTS: Overall, 16.6% of patients reported at least some degree of loneliness. Partnership status, depression, and anxiety were significantly associated with loneliness. Individuals living in a partnership experienced lower levels of loneliness (p < 0.001), while higher levels of depression and anxiety were associated with increased loneliness (p < 0.001). In multivariable logistic regression analysis, having a steady partnership was associated with a significantly lower risk of loneliness (OR 0.18, 95%CI [0.13-0.24]). Symptoms of depression (OR 1.49, 95%CI [1.31-1.71]) or anxiety (OR 1.29, 95%CI [1.13-1.47]) or being frail (OR 3.97, 95%CI [2.99-5.28]) were independently associated with an increased risk of being lonely. CONCLUSIONS: Nearly one in five PC survivors experienced some to severe loneliness in this study, with notable associations with partnership status, symptoms of depression or anxiety and frailty. The findings emphasize the importance of addressing loneliness as part of comprehensive care for PC survivors.
J Cancer Res Clin Oncol
· 2026 Jun · PMID 42288668
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BACKGROUND: Metabolic reprogramming, particularly enhanced lipid synthesis, is a hallmark of cancer that supports tumor growth and progression. However, the transcriptional regulators controlling this process in hepatoce...BACKGROUND: Metabolic reprogramming, particularly enhanced lipid synthesis, is a hallmark of cancer that supports tumor growth and progression. However, the transcriptional regulators controlling this process in hepatocellular carcinoma (HCC) remain incompletely understood. METHODS: A genome-wide CRISPR/Cas9 knockout screen identified ZNF217 as a key regulator of lipid metabolism in HCC. The regulatory effects of ZNF217 were analyzed using RNA sequencing, RT-qPCR, western blotting, and dual luciferase reporter assay. Intracellular lipid content was assessed using flow cytometry, oil red O staining, and triglyceride/cholesterol detection kits. Cell proliferation, migration, and invasion were assessed in vitro. In vivo tumor growth and metastasis were evaluated using nude mouse models. Clinical relevance was analyzed using immunohistochemical (IHC) staining, Kaplan-Meier survival analysis. RESULTS: We identify the transcription factor ZNF217 as a key activator of de novo lipogenesis in HCC. ZNF217 binds to and transactivates the promoters of critical lipogenic enzymes, including fatty acid synthase (FASN) and acetyl-CoA carboxylase 1 (ACC1). ZNF217-driven lipid synthesis, cell proliferation, migration, and invasion were dependent on FASN expression, as demonstrated by pharmacological inhibition and genetic knockdown. ZNF217 overexpression promoted HCC tumor growth and lung metastasis in a FASN-dependent manner in vivo. Clinically, ZNF217 was significantly upregulated in HCC tissues, positively correlated with FASN expression, and associated with poor patient survival. CONCLUSIONS: Our findings establish ZNF217 as a novel transcriptional regulator of lipid metabolism in HCC, linking its oncogenic function to the activation of the lipogenic pathway, and propose the ZNF217-FASN axis as a candidate therapeutic target for HCC treatment.
Tang S, Yan X, Gong T
… +3 more, Zhi W, Gao Y, Han Y
J Cancer Res Clin Oncol
· 2026 Jun · PMID 42287455
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BACKGROUND & AIMS: Transarterial chemoembolization (TACE) combined with targeted therapy and immunotherapy is a promising approach for intermediate and advanced hepatocellular carcinoma (HCC). This study aimed to compare...BACKGROUND & AIMS: Transarterial chemoembolization (TACE) combined with targeted therapy and immunotherapy is a promising approach for intermediate and advanced hepatocellular carcinoma (HCC). This study aimed to compare the efficacy and safety of TACE plus tislelizumab and tyrosine kinase inhibitors (TKIs) versus TACE alone. METHODS: This retrospective study analyzed patients with intermediate and advanced HCC treated from February 2018 to September 2023. Patients were divided into two groups: the combination therapy group (TACE plus tislelizumab and TKIs) and the monotherapy group (TACE alone). The primary endpoint was progression-free survival PFS), and secondary endpoints included objective response rate (ORR), disease control rate (DCR), overall survival (OS), and safety. Cox regression, sensitivity analysis, Kaplan-Meier survival curves, and restricted mean survival time (RMST) analysis were performed to assess the robustness of the PFS benefit. RESULTS: A total of 62 patients were included (30 in the combination group, 32 in the monotherapy group), with balanced baseline characteristics. After a median follow-up of 33.3 months, median PFS was 11.7 months in the combination group and 3.8 months in the monotherapy group (hazard ratio [HR], 0.43; 95% confidence interval [CI], 0.24-0.77; P = 0.0034). This benefit persisted after multivariable adjustment (adjusted HR, 0.28; 95% CI 0.14-0.57; P < 0.001) and was confirmed by sensitivity and RMST analyses at 12, 24, 36, and 48 months (all P < 0.01). The combination group also showed favorable outcomes in secondary endpoints including ORR, DCR, and OS rates. Four patients (13.3%) in the combination group underwent downstaging to curative treatment, with PFS ranging from 14.8 to 49.2 months. Grade ≥ 3 adverse events occurred in 10.0% of the combination group and in none of the monotherapy group, with no treatment-related deaths. CONCLUSIONS: TACE combined with tislelizumab and TKIs significantly improved PFS compared with TACE alone, with a manageable safety profile, in patients with intermediate and advanced HCC. This regimen may offer a potential conversion option for selected patients in this population.
Apuhan T, Demir O, Sagnak Yilmaz Z
… +3 more, Karaman E, Turkyilmaz A, Cebi AH
J Cancer Res Clin Oncol
· 2026 Jun · PMID 42286372
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Lynch syndrome is an inherited cancer predisposition syndrome caused by germline pathogenic variants in mismatch repair (MMR) genes and is primarily associated with colorectal and endometrial cancers. Classically, Lynch...Lynch syndrome is an inherited cancer predisposition syndrome caused by germline pathogenic variants in mismatch repair (MMR) genes and is primarily associated with colorectal and endometrial cancers. Classically, Lynch syndrome-associated tumors exhibit microsatellite instability (MSI) and loss of MMR protein expression on immunohistochemistry (IHC); therefore, MSI and IHC are routinely used in screening algorithms to support diagnostic evaluation. ; Methods: In this study, we present the molecular and pathological characteristics of four cases from three unrelated families carrying the same MSH2 variant [c.70C > T (p.Gln24Ter)], interpreted as pathogenic, who were diagnosed with breast and colorectal cancer. MSI analysis and MMR protein expression were evaluated in available tumor tissues. ; Results: Preserved MMR protein expression was observed in three cases, and two cases were microsatellite stable (MSS), whereas only one case demonstrated loss of MMR protein expression and an MSI-high phenotype consistent with the classical Lynch syndrome profile. These findings suggest that individuals carrying the same MSH2 variant may exhibit heterogeneous tumor-level MMR/MSI phenotypes. Early truncating variants in MSH2 may allow partially functional protein production via alternative translation initiation, potentially limiting complete loss of MMR function. Variability in somatic second-hit mechanisms and tumor-specific molecular pathways may also contribute to this heterogeneity. ; Conclusion: In conclusion, Lynch syndrome tumor biology may be more heterogeneous than expected, and MSI and IHC should not be interpreted in isolation as exclusionary tests for an underlying germline MMR variant, but rather as markers of tumor-level biological consequences. Therefore, germline findings, tumor characteristics, and family history should be evaluated together in Lynch syndrome diagnosis and risk assessment.