Clinical & Translational Oncology[JOURNAL]
Sun
200 papers
Dynamic assessment of proliferation to guide response-adapted therapy in the setting of neoadjuvant chemotherapy in ER+/HER2- breast cancer.
Saghir H, Veerla S, Loman N … +1 more , Kimbung S
Transl Oncol · 2026 Jan · PMID 41242143 · Full text
Biomarkers for evaluating response to neoadjuvant chemotherapy (NACT) in ER+/HER2- breast cancer remain limited. This study explores the impact of NACT on tumor proliferation dynamics and its association with relapse-fre...
Biomarkers for evaluating response to neoadjuvant chemotherapy (NACT) in ER+/HER2- breast cancer remain limited. This study explores the impact of NACT on tumor proliferation dynamics and its association with relapse-free interval (RFI) among 175 patients with early ER+/HER2- breast tumors. Proliferation was assessed at baseline, after completing two NACT cycles, and in the residual tumor using Ki67 immunohistochemistry (IHC) and two gene expression assays (GEAs): SSP-Ki67 and AURKA score. Slight to moderate agreement was observed between IHC and GEAs, with IHC-Ki67 consistently classifying more tumors as highly proliferative compared to SSP-Ki67 at both baseline and surgery. Proliferation status at baseline was not prognostic for RFI using either IHC-Ki67 or SSP-Ki67 in our cohort. However, patients with persistently high proliferation after two NACT cycles or in the residual tumor following NACT were at increased risk of relapse, with SSP-Ki67 outperforming IHC-Ki67 in identifying patients with a poorer prognosis. Our results demonstrate that tumor proliferation status measured after brief exposure to NACT or in the residual tumor post-NACT holds prognostic value and may inform the tailoring of post-neoadjuvant treatment strategies in patients with early luminal breast cancer, and that relying on IHC-Ki67 to evaluate treatment response may potentially lead to overtreatment.
Identification of cuproptosis-related subtypes, construction of a prognosis model, and tumor microenvironment landscape in multiple myeloma.
Xu L, Zhang H, Wang K … +14 more , Gao X, Bu W, Yu D, Hu K, Zhang Q, Wang G, Wu X, Jia X, Peng Y, Song D, Yi H, Cai H, Shi J, Feng Q
Transl Oncol · 2026 Jan · PMID 41240503 · Full text
Multiple myeloma (MM) is a challenging hematologic malignancy with increasing incidence. Cuproptosis, a copper-dependent form of cell death associated with mitochondrial metabolism and protein lipoylation, remains unexpl...
Multiple myeloma (MM) is a challenging hematologic malignancy with increasing incidence. Cuproptosis, a copper-dependent form of cell death associated with mitochondrial metabolism and protein lipoylation, remains unexplored in MM. This study aims to investigate this connection using transcriptome profiling and clinical data from the Gene Expression Omnibus database. Analysis of copper death-related genes (CRGs) revealed significant expression differences in 6 out of 12 CRGs, with GLS, ATP7B, PDHA1, MTF1, CDKN2A and DLAT showing notable correlations with survival of MM patients. Unsupervised clustering identified two cuproptosis molecular subtypes in MM patients, which exhibited significant associations with clinical features, prognosis, and immune cell infiltration. These subtypes identified 186 potential MM target genes, enriched in protein binding and intracellular/extracellular structure regulations. Five key biomarkers (CKS2, HGF, HSP90B1, PRIM1, and VCAM1) effectively stratified patients into high- and low-risk groups, strongly correlated with age, ISS stage, serum LDH content, and survival. Functional enrichment analysis revealed differential genes were involved in regulating cell membrane structure, protein binding, and metabolic pathways. High- and low-risk groups displayed distinct immune cell infiltration patterns and immune checkpoint expressions. In vitro experiments, the combination of elesclomol (a copper ion carrier) and bortezomib (Bortezomib) demonstrated a synergistic anti-myeloma effect through excessive intracellular reactive oxygen species generation. This study provides valuable insights into the role of CRGs in MM, potentially aiding in prognosis prediction and the development of effective, personalized therapeutic strategies.
ITLN1, orchestrated by the IFNγ-IRF1 axis, suppresses hepatocellular carcinoma proliferation via ERK1/2 activation.
Yuan T, Liu J, Zhu R … +5 more , Li J, Huang Z, Liang H, Tao H, Zhang E
Transl Oncol · 2026 Jan · PMID 41218553 · Full text
BACKGROUND: Intelectin 1 (ITLN1) is a recently discovered secretory adipokine with pivotal functions in the innate immune system, inflammation, and the facilitation of glucose uptake. Nonetheless, its exact functions in...
BACKGROUND: Intelectin 1 (ITLN1) is a recently discovered secretory adipokine with pivotal functions in the innate immune system, inflammation, and the facilitation of glucose uptake. Nonetheless, its exact functions in hepatocellular carcinoma (HCC) remain not fully elucidated. METHODS: In this study, ITLN1 was identified as a clinically significant secretory adipokine linked to HCC, validated through qRT-PCR, western blot, immunohistochemistry, and TCGA data. Its role in HCC was explored using CCK-8, clone formation, EdU, migration, and cell cycle assays, alongside xenograft tumor experiments. RNA sequencing, luciferase reporter assays, and ChIP assays confirmed ITLN1's molecular mechanisms in inhibiting HCC proliferation. RESULTS: Our study revealed that ITLN1 expression was significantly downregulated in HCC tissues compared to adjacent non-tumor tissues, and its reduced expression was associated with poor overall survival. Functionally, ITLN1 attenuated HCC proliferation in a cell cycle arrest manner via activation of ERK1/2 signaling. We also identified transcription factor interferon regulatory factor 1 (IRF1) as a regulator of ITLN1 through bioinformatics analysis and affirmed the binding site on the ITLN1 promoter. Furthermore, interferon-gamma (IFNγ), a classic upstream cytokine of IRF1, could promote ITLN1 expression through IRF1. Subsequently, the IFNγ-IRF1-ITLN1 axis was identified and found to inhibit HCC cell proliferation and cell cycle progression. CONCLUSIONS: In summary, our study found that ITLN1, regulated by IFNγ-IRF1 axis, suppresses HCC proliferation by constitutively activating ERK1/2 signaling and holds promise as a prospective prognostic indicator and a plausible therapeutic target for HCC.
Magrolimab (Hu5F9-G4) promotes macrophage M1 polarization and is associated with enhanced autophagy in colorectal cancer.
Lin WR, Liu WQ, Alburiahi TAH … +4 more , Chen RB, Lu HP, Dong J, Yang J
Transl Oncol · 2026 Jan · PMID 41218551 · Full text
BACKGROUND: The role of macrophage infiltration in colorectal cancer (CRC) and its implications for prognosis remains uncertain. While macrophage immune checkpoint inhibitors have shown efficacy in treating solid tumors,...
BACKGROUND: The role of macrophage infiltration in colorectal cancer (CRC) and its implications for prognosis remains uncertain. While macrophage immune checkpoint inhibitors have shown efficacy in treating solid tumors, their impact on CRC progression and immune regulation is unclear. PURPOSE: This study investigates the effect of the macrophage immune checkpoint inhibitor Hu5F9-G4 on the immune microenvironment, macrophage behaviour, and CRC progression to identify potential therapeutic targets. METHODS: A total of 73 CRC samples were analysed to evaluate the association between M2d macrophage infiltration and prognosis. In vitro studies examined the effect of Hu5F9-G4 on M2d-to-M1 polarization, CRC cell proliferation, and migration. In vivo experiments assessed tumor growth and macrophage polarization in CRC-bearing mice treated with Hu5F9-G4. Single-cell transcriptome analysis, bioinformatics, and clinical validations were conducted to identify potential autophagy-related therapeutic targets. RESULTS: High M2d macrophage infiltration correlated with poor CRC prognosis. Hu5F9-G4 treatment significantly promoted M2d-to-M1 polarization, inhibited CRC cell proliferation and migration, and increased autophagy in macrophages. In vivo, Hu5F9-G4 reduced tumor growth and modified immune cell populations. Integrative analyses identified CDKN1A and MAP1LC3B as potential therapeutic targets linked to the autophagy pathway. CONCLUSION: Hu5F9-G4 demonstrates potential as a therapeutic agent in CRC by promoting M2d-to-M1 macrophage polarization, suppressing tumor progression, and influencing the autophagy pathway. These findings highlight CDKN1A and MAP1LC3B as promising targets for CRC therapy.
Clinical significance and molecular mechanism of CDX2-CBX3 regulatory axis in lung adenocarcinoma progression.
Liu S, Zhao Q, Ren D … +3 more , Kong L, Zhao H, Duan G
Transl Oncol · 2026 Jan · PMID 41218550 · Full text
Lung adenocarcinoma (LUAD) remains a leading cause of cancer-related mortality, with chemotherapy resistance and tumor heterogeneity posing significant challenges. The Chromobox (CBX) protein family, crucial epigenetic r...
Lung adenocarcinoma (LUAD) remains a leading cause of cancer-related mortality, with chemotherapy resistance and tumor heterogeneity posing significant challenges. The Chromobox (CBX) protein family, crucial epigenetic regulators in tumor progression, has not been systematically characterized in LUAD. This study aimed to develop a CBX-based molecular classification system for LUAD and explore the mechanistic role of the CDX2-CBX3 regulatory axis in tumor progression. Through multiomics analysis of TCGA-LUAD data, four distinct CBX subtypes were identified, each associated with variations in survival, clinical stage, DNA repair pathway activation, and immune cell infiltration. Mechanistic investigations (ChIP-qPCR, luciferase assays, and gain/loss-of-function experiments) confirmed that CDX2 directly upregulates CBX3 transcription via conserved promoter binding. CDX2 overexpression enhanced migration, invasion, and xenograft growth, whereas CBX3 knockdown suppressed these phenotypic changes. In conclusion, this study defines clinically relevant CBX molecular subtypes in LUAD and reveals the CDX2-CBX3 transcriptional cascade as a novel driver of tumor progression, offering potential targets for precision therapy.
Development and validation of a nomogram for predicting the risk of malignancy in intraductal papillary neoplasms: a retrospective study.
Pang H, Nanding A, Kang W … +6 more , Song L, Zhang J, Liu J, Ziqi Z, Zhang G, Shan M
Transl Oncol · 2026 Jan · PMID 41202567 · Full text
OBJECTIVE: Development and validation of a simple, accurate nomogram for predicting the risk of malignancy in intraductal papillary neoplasms (IPNs). BACKGROUND: Some studies have explored the independent risk factors as...
OBJECTIVE: Development and validation of a simple, accurate nomogram for predicting the risk of malignancy in intraductal papillary neoplasms (IPNs). BACKGROUND: Some studies have explored the independent risk factors associated with malignant IPNs, but no validated predictive model has been developed to help clinicians assess the probability of malignancy in patients with IPNS. METHODS: This case-control study included 6646 patients with IPNs which date came from single-center. A nomogram predicting the malignant probability of IPNs was developed by incorporating independent predictors identified through multivariate logistic regression analysis, and the nomogram was externally validated. RESULTS: Age ≥50 years, bloody discharge, palpable tumor, postmenopausal status, multiple tumors, unclear boundaries, blood flow signals, tumor size ≥15 mm, distance from the nipple ≥1 cm, and the presence of tumor calcification were identified as independent risk factors for predicting malignancy in IPNs. A nomogram was constructed using these 10 factors, yielding a C-index and the area under the curve of 0.871 (95% CI 0.857-0.884) in the training set and 0.874 (95% CI 0.858-0.890) in the validation set. Moreover, the calibration curves demonstrated a high level of agreement between predicted and actual values, and clinical decision curve analysis and clinical impact curve visually confirmed the satisfactory clinical utility of the model. According to the nomogram, we suggest that IPNs patients with a malignant probability <10% can choose regular follow-up rather than surgical treatment. CONCLUSION: Our nomogram may assist clinicians in identifying IPNs with varying degrees of malignant risk, facilitating decision-making for personalized treatment in clinical practice.
Utilization of ultrasound combined with Ki-67 and CESM quantitative parameters to predict pathological complete response following neoadjuvant chemotherapy in triple-negative breast cancer.
Zhang Y, Yuan MQ, Jia TL … +1 more , Guo J
Transl Oncol · 2026 Jan · PMID 41192151 · Full text
OBJECTIVE: To evaluate the predictive value of ultrasound parameters combined with Ki-67 and contrast-enhanced spectral mammography (CESM) for assessing pathological complete response (pCR) following neoadjuvant chemothe...
OBJECTIVE: To evaluate the predictive value of ultrasound parameters combined with Ki-67 and contrast-enhanced spectral mammography (CESM) for assessing pathological complete response (pCR) following neoadjuvant chemotherapy (NAC) in triple-negative breast cancer (TNBC). METHODS: This retrospective study included 78 TNBC patients who underwent surgery after NAC and were stratified into pCR and non-pCR (nPCR) groups based on postoperative pathology. Baseline ultrasound imaging was conducted upon admission. Primary tumor ultrasound features and change rates in tumor longest diameter (△D2, △D4) after 2 and 4 NAC cycles were analyzed. CESM was performed pre-treatment and after two cycles to calculate △CNR (percentage reduction in relative enhancement grayscale value). Univariate and multivariate logistic regression analyses were employed to identify independent predictors of pCR. RESULTS: Univariate analysis revealed significant differences in △D2, △D4, retromammary space disappearance, Ki-67 expression, and △CNR between the pCR and nPCR groups following 2 and 4 cycles (P< 0.05). Variables with P< 0.05 were included in multivariate binary logistic regression. △D4, △CNR, and Ki-67 were identified as independent predictors of pCR in TNBC (OR=1.064, P= 0.041; OR=1.081, P= 0.016; OR=0.140, P= 0.005, respectively). The combined predictive model yielded an AUC of 0.869 (95 % CI: 0.774-0.963), with a sensitivity of 84.0 % and specificity of 84.9 %. CONCLUSION: The integration of △D4, △CNR, and Ki-67 offers clinical utility in predicting NAC response in TNBC.
Nuclear factor E2 p45-related factor (NRF2) and peroxiredoxin 6 tissular expression as prognostic biomarkers for advanced HPV-negative squamous cell carcinoma of the oropharynx.
Philouze P, Benzerdjeb N, Malésys C … +8 more , Wozny AS, Soumboundou M, Kobler A, Jung AC, Burgy M, Céruse P, Alphonse G, Rodriguez-Lafrasse C
Transl Oncol · 2026 Jan · PMID 41187427 · Full text
OBJECTIVES: Non-HPV-induced squamous cell carcinomas (SCC) of the oropharynx have a poorer prognosis than HPV-induced cancers because they are more radio- and chemoresistant. Currently, no predictive biomarker exists for...
OBJECTIVES: Non-HPV-induced squamous cell carcinomas (SCC) of the oropharynx have a poorer prognosis than HPV-induced cancers because they are more radio- and chemoresistant. Currently, no predictive biomarker exists for survival outcome in this type of tumor. NRF2 is a nuclear transcription factor that regulates the expression of cytoprotective genes, and peroxiredoxin 6 is one of the proteins regulated by NRF2. Both are potentially involved in the resistance to treatments as they play a central role in the response to oxidative stress. MATERIAL AND METHODS: In a retrospective cohort study of 53 patients with advanced HPV-negative squamous cell carcinomas of the oropharynx, we studied the correlation between clinical characteristics, response to treatment (surgery + radiotherapy), patient survival, and the expression of NRF2 and peroxiredoxin 6 in pre-treatment tumor biopsies. We prepared Tissue Micro Arrays (TMA) before performing immunohistochemistry analyses. RESULTS: For a given patient, prior to any treatment, NRF2 and peroxiredoxin 6 are overexpressed in tumor tissue compared with healthy tissue. Moreover, patients with high NRF2 expression tended to have poorer progression-free survival (p = 0,09). Patients with high expression of peroxiredoxin 6 had significantly worse progression-free survival and overall survival (p = 0.015 and p < 0.01, respectively). The combination of high NRF2 and peroxiredoxin 6 expression was associated with even worse survival outcomes (p < 0.01and p = 0.01, respectively). CONCLUSION: Elevated expression levels of peroxiredoxin 6, either alone or in combination with NRF2, are poor prognostic indicators for patient survival.
Drug-tolerant persister cells in head and neck squamous cell carcinoma: Molecular mechanisms and therapeutic opportunities.
Ling HH, Huang HY, Huang CM … +6 more , Yasir M, Ko CC, Yadav VK, Kuo KT, Yeh CT, Tsai JT
Transl Oncol · 2026 Jan · PMID 41166929 · Full text
Although treatments for HNSCC have improved, the cancer is still challenging because many patients tend to develop the disease again nearby and often have poor recovery. Since drug-tolerant persister (DTP) cells display...
Although treatments for HNSCC have improved, the cancer is still challenging because many patients tend to develop the disease again nearby and often have poor recovery. Since drug-tolerant persister (DTP) cells display a wide range of types and unique genetic characteristics, nonhormonal endocrine therapies, including chemotherapy, targeted therapy and immunotherapy, are ineffective in eliminating these cells. DTP cells evade elimination by entering a reversible dormant state characterized by altered metabolism, enhanced DNA repair capacity, and modified immune escape mechanisms, all of which promote the cells' survival and treatment failure. Platinum-based chemotherapy, widely prescribed for HNSCC, reduces tumor size but fails to confer long-term benefits because of the strong treatment resistance of DTP cells. These cells also exhibit resistance to tyrosine kinase inhibitors by activating alternative signaling pathways. Alternative survival pathways are also activated in DTP cells when targeted therapies such as those using epidermal growth factor receptor inhibitors are used. Although programmed death 1/programmed death ligand 1 inhibitors are exciting new treatments, their effect is hampered by DTP cells that affect the immune system. This review examines the ways DTP cells make HNSCC tumor cells resistant to treatment by looking at metabolic reprogramming, DNA methylation alterations and the microenvironment of the tumor. This review further explores strategies for targeting metabolic dependencies, inhibiting DNA repair, and combining therapeutic approaches, all of which can mitigate DTP cell-mediated recurrence. Advancing strategies that specifically target DTP cells could enhance HNSCC management by reducing recurrence and improving overall prognosis.
Expression of Bacillus in colorectal tissues is associated with improved cetuximab therapy for patients with metastatic colorectal cancer.
Hsu HC, Chung HY, You JF … +4 more , Lee YS, Chang JS, Hou HH, Wang CW
Transl Oncol · 2026 Jan · PMID 41161250 · Full text
BACKGROUND: Metastatic colorectal cancer (mCRC) remains the second leading cause of cancer-related deaths worldwide. Previous studies have shown that somatic mutations and gut microbiota contribute to mCRC progression. H...
BACKGROUND: Metastatic colorectal cancer (mCRC) remains the second leading cause of cancer-related deaths worldwide. Previous studies have shown that somatic mutations and gut microbiota contribute to mCRC progression. However, whether microbiota profiles in colorectal tissues are related to mCRC prognosis and correlate with patients' somatic mutations remains unclear. OBJECTIVES: We aimed to characterize microbiota expression profiles in formalin-fixed paraffin-embedded (FFPE) colorectal cancer tissues of patients with mCRC to analyze their prognostic role. METHODS: FFPE cancer tissues from 65 patients with mCRC were divided into two groups based on overall survival (OS > 4years, OS < 4 years). These groups were analyzed for microbiota expression profiles, somatic mutations, and treatment outcomes. RESULTS: Higher relative expression of Bacillus and Coprococcus in metastatic colorectal tumor tissues were associated with longer overall survival (hazard ratio [HR] = 0.5; p = 0.008 and 0.013, respectively), while higher Streptococcus expression had a shorter overall survival (HR = 2.0; p = 0.011). Patients with PTPRT/D and without KMT2D mutations had higher Bacillus expression in colorectal tumor tissues (all p < 0.05). Importantly, patients with higher Bacillus expression who received cetuximab (an epidermal growth factor receptor [EGFR] inhibitor) therapy had longer overall survival (median 34.1 months vs 19.4 months; HR = 0.5; p = 0.029) and progression-free survival (median 12.6 months vs 6.2 months; HR = 0.5, p = 0.0019) compared with those with lower relative expression. CONCLUSIONS: Our study suggests that Bacillus expression in colorectal tissues is associated with improved outcomes in patients with mCRC receiving cetuximab therapy.
Application of CTC-derived spheroid for drug screening toward personalized treatment in patients with breast cancer.
Chou HH, Che TF, Lee KJ … +8 more , Chen SC, Chen JY, Huang YJ, Lim SC, Huang SC, Tsai CL, Chang YC, Tsai CN
Transl Oncol · 2026 Jan · PMID 41151488 · Full text
PURPOSE: Tumor heterogeneity and drug resistance remain key challenges in breast cancer management. While organoid cultures can be established from resected tumor specimens, patients undergoing systematic treatment often...
PURPOSE: Tumor heterogeneity and drug resistance remain key challenges in breast cancer management. While organoid cultures can be established from resected tumor specimens, patients undergoing systematic treatment often lack accessible tissue for ex vivo drug testing. Circulating tumor cells (CTCs) offer a minimally invasive alternative. The purpose of this study was to establish a clinically feasible workflow that integrates CTC enumeration and CTC-derived spheroid drug screening to overcome the limitations of tissue-dependent organoid models and enable personalized treatment in breast cancer. METHODS: CTCs were isolated from 34 newly diagnosed breast cancer patients using a liposome-tethered supported lipid bilayer (LIPO-SLB) microfluidic platform functionalized with anti-EpCAM antibodies. Thirteen patients undergoing systemic therapy and relapse were further assessed using CTC-spheroid culture for ex vivo drug screening. Hormone receptor expression and genomic mutation profiles were integrated with drug testing. One relapsed case underwent pre- and post-treatment spatial transcriptomic analysis (Xenium in situ). RESULTS: CTC and CTC-cluster counts significantly declined post-treatment in responders (p=0.044 and p=0.0264, respectively), but not in non-responders. CTC-spheroids were successfully generated in all 13 cases, enabling ex vivo drug testing. Effective therapies were identified in 9 patients (69.2%), of whom 7 achieved partial responses and 1 achieved stable disease; one patient did not receive the suggested treatment. Ex vivo drug sensitivity results correlated with clinical outcomes. Integrating CTC-based drug testing, hormone receptor expression in CTCs, and genomic DNA mutation profile further improved prediction of radiological response. Spatial transcriptomics revealed therapy-induced clonal shifts, with resistant subpopulations characterized by over-expression of chemoresistant gene, EIF4EBP1. CONCLUSION: This study demonstrates that CTC-derived spheroid drug screening provides actionable therapeutic guidance when tissue is unavailable. Combined with hormone receptor and genomic profiling, this liquid biopsy-based platform enables personalized treatment, and dynamic monitoring of resistance in breast cancer.
Exploring the optimal treatment modality for non-small cell lung cancer after stage N2 surgery based on the SEER database and constructing a predictive model for the beneficiary population.
Liu L, Sun L, Guo L … +3 more , Mao Y, Li C, Wang Y
Transl Oncol · 2025 Dec · PMID 41135328 · Full text
This study aimed to identify the optimal postoperative adjuvant treatment for operable N2 stage NSCLC and develop a predictive model for predicting survival benefit. A total of 951 N2 stage NSCLC patients from the SEER d...
This study aimed to identify the optimal postoperative adjuvant treatment for operable N2 stage NSCLC and develop a predictive model for predicting survival benefit. A total of 951 N2 stage NSCLC patients from the SEER database were divided into POCT (postoperative adjuvant chemotherapy) and POCRT (postoperative adjuvant chemoradiotherapy) groups. PSM (Propensity Score Matching) was used to minimize bias. The primary endpoint was OS (overall survival). Survival rates between the two groups before and after PSM were compared using Kaplan-Meier survival curves. Robust Cox regression analysis after PSM identified independent prognostic factors, and a logistic regression prediction model was established based on the training set. Model validity was validated using AUC (Area Under Curve) and calibration curves. Clinical decision analysis was employed to evaluate the predictive model's practical value in clinical decision-making. The model incorporated Age, Sex, T stage, and LODDS as predictors. The training set AUC was 0.723, while the internal validation set and external validation set AUC values were 0.710 and 0.729, respectively, indicating good predictive capability. The patients in the POCT group were exploratively divided into high-benefit and low-benefit groups. Survival analysis revealed superior outcomes in the high-benefit cohort receiving adjuvant chemotherapy alone. In summary, this SEER-based observational analysis demonstrates that patients with operable N2-stage NSCLC achieve better outcomes with POCT alone compared to POCRT. Furthermore, the predictive model effectively quantifies patient benefit.
Knockdown of LRP11-AS1 inhibits papillary thyroid tumor growth by modulating miR-615-3p/AKT2 axis.
Li P, Wu Z, Li L … +3 more , Chen Y, Zhang C, Zheng W
Transl Oncol · 2025 Dec · PMID 41130019 · Full text
Patients with papillary thyroid cancer (PTC) who experience local recurrence and distant metastases have a poor clinical prognosis and low survival rate. In this study, the expression of LRP11-AS1 was evaluated in both t...
Patients with papillary thyroid cancer (PTC) who experience local recurrence and distant metastases have a poor clinical prognosis and low survival rate. In this study, the expression of LRP11-AS1 was evaluated in both tissue samples from patients with papillary thyroid cancer and in PTC cell lines. We observed significant overexpression of LRP11-AS1 in both PTC tissues and PTC cell lines and inhibitory effects of LRP11-AS1 knockdown on the growth and migration of PTC cells. Mechanistically, knockdown of LRP11-AS1 led to upregulation of miR-615-3p, overexpression of miR-615-3p decreased the expression of both LRP11-AS1 and AKT2. The dual-luciferase reporter assay confirmed the inhibitory effect of miR-615-3p on the expression of LRP11-AS1 and AKT2. Knockdown of LRP11-AS1 inhibited in vivo growth of PTC tumor in nude mice model. LRP11-AS1 exhibited potential oncogenic effects in PTC by regulating the miR-615-3p/AKT2 axis, suggesting that LRP11-AS1 could serve as a potential diagnostic biomarker and therapeutic target in PTC.
Propofol inhibits glioma growth by blocking the formation of the NF-κB/LGI4 feedback loop to activate TP53 self-transcription.
Wang Z, Zhang LN, Wu T … +2 more , Pan X, Li L
Transl Oncol · 2025 Dec · PMID 41130018 · Full text
Accumulating evidence has clarified the anti-cancer function of propofol (PPF) in glioma. However, the underlying regulatory mechanism still remains not fully understood. Our current study screens out a novel gene-leucin...
Accumulating evidence has clarified the anti-cancer function of propofol (PPF) in glioma. However, the underlying regulatory mechanism still remains not fully understood. Our current study screens out a novel gene-leucine-rich glioma-inactivated 4 (LGI4), as a target molecule of PPF, and shows that 10 μg/ml of PPF (a clinically relevant concentration commonly used in multiple previous studies) suppresses the NF-κB signaling pathway to inhibit LGI4 transcription in glioma cells. Clinically, the expression of LGI4 is upregulated in glioma tissues, and its high expression correlates with unfavorable prognosis. Functionally and mechanically, LGI4 promotes tumor growth through blocking TP53 self-transcription by binding to p53 and hindering its nuclear import. Significantly, LGI4 is not only transcriptionally activated by the NF-κB signaling pathway but also feedback activates NF-κB signaling by inhibiting the interaction of IKIP with the IKKα/IKKβ/NEMO complex. Importantly, PPF treatment can break this positive feedback loop. Collectively, our findings uncover that PPF upregulates p53 expression by disrupting the NF-κB/LGI4 feedback loop, thereby inhibiting glioma growth, highlighting it is a potential therapeutic target for future glioma treatment.
Longitudinal serum metabolomics predicts therapeutic outcome in acute myeloid leukemia.
Cai Q, Liu W, Yan C … +10 more , Li J, Huang Y, Li X, Yang Q, Wei X, Yang H, Zhang G, Yang T, Chen Y, Hu J
Transl Oncol · 2025 Dec · PMID 41115383 · Full text
Acute myeloid leukemia (AML) is the most common acute leukemia in adults, with approximately 50 % of patients failing to achieve remission during initial treatment and progressing to refractory AML. Metabolomics, a techn...
Acute myeloid leukemia (AML) is the most common acute leukemia in adults, with approximately 50 % of patients failing to achieve remission during initial treatment and progressing to refractory AML. Metabolomics, a technology directly linked to clinical phenotypes, offers more precise susceptibility biomarkers compared to genomics and epigenetics. Our study compares metabolic samples collected at multiple time points pre- and after-chemotherapy, performs longitudinal integrated analysis to characterize dynamic alterations, and assesses the temporal impacts of therapeutic responses. Four metabolites-pseudouridine, O-phospho-L‑serine, l-aspartate, and 2-deoxy-d-ribose 1-phosphate-were significantly elevated in AML patients, mechanistically linking dysregulated nucleotide biosynthesis and adaptive amino acid metabolic reprogramming to leukemogenic proliferation.Longitudinal sampling during AML treatment revealed temporal metabolic changes, identifying key metabolites and pathways associated with therapeutic responses.By integrating pre- and after-treatment metabolic index with clinical indicators, we developed predictive models for treatment outcomes. The pre-treatment metabolic model (AUC=0.9143, 95 % CI 0.816-1) and the after-treatment metabolic index (AUC=0.9136, 95 % CI 0.83-1) both demonstrated excellent predictive performance for AML therapeutic outcomes. In conclusion, our findings underscore the potential of targeting glycolipid synthesis and amino acid metabolism to improve clinical outcomes. The dynamic metabolic reprogramming landscape serves as a robust indicator of AML treatment efficacy, offering novel directions for precision therapy in AML.
Malignant ascites in ovarian cancer: New advances and translational opportunities.
Boo KH, Lee G, Song M
Transl Oncol · 2025 Dec · PMID 41106271 · Full text
Malignant ascites is a defining and clinically challenging feature of advanced ovarian cancer, driving peritoneal dissemination, therapeutic resistance, and poor clinical outcomes. Beyond its traditional description as a...
Malignant ascites is a defining and clinically challenging feature of advanced ovarian cancer, driving peritoneal dissemination, therapeutic resistance, and poor clinical outcomes. Beyond its traditional description as a protein-rich fluid, high-resolution profiling now reveals ascites as an active ecosystem that enforces vascular leakage, creates dynamic interactions among cellular, acellular, and environmental components, fuels cellular reprograms, and builds profound immune suppression. In this review, we first synthesize established knowledge on ascites formation and composition, and then delineate how this milieu reshapes tumor, stromal, and immune compartments, altering their fate and function. We also integrate current diagnostics and map the therapeutic landscape spanning vascular permeability control, effective locoregional chemotherapy, cellular reprogramming, and stress/metabolic interventions, alongside palliative drainage devices. A deeper understanding of the dynamic interactions and regulatory mechanisms within malignant ascites provides a foundation for developing new therapeutic strategies to overcome its clinical challenges and improve outcomes for ovarian cancer patients.
Proteomic profiling links complement activation to thrombosis in JAK2V617F myeloproliferative neoplasms.
De Moner B, Martinez-Sanchez J, Escribano-Serrat S … +7 more , Ramos A, Moreno-Castaño AB, Arellano-Rodrigo E, Escolar G, Carreras E, Álvarez-Larrán A, Diaz-Ricart M
Transl Oncol · 2025 Dec · PMID 41101219 · Full text
BACKGROUND: Myeloproliferative neoplasms (MPNs) are associated with a high risk of thrombotic complications, particularly splanchnic vein thrombosis (SVT). This study aimed to elucidate the proteomic signature of JAK2V61...
BACKGROUND: Myeloproliferative neoplasms (MPNs) are associated with a high risk of thrombotic complications, particularly splanchnic vein thrombosis (SVT). This study aimed to elucidate the proteomic signature of JAK2V617F-mutated MPN patients with and without SVT, focusing on dysregulated pathways contributing to thrombotic risk. METHODS: We conducted a comprehensive proteomic analysis of plasma samples from 28 JAK2V617F-mutated MPN patients (22 with SVT, 6 without thrombosis) and 6 healthy controls. Proteins were quantified using TMT labeling and nanoLC-MS/MS, followed by multivariate and univariate statistical analyses. FINDINGS: A total of 275 high-confidence proteins were identified. Compared to controls, MPN patients exhibited significant dysregulation of complement and coagulation pathways, with upregulation of complement components (C1QA, C1QB, C1QC, C7) and endothelial adhesion molecules (VCAM1, ICAM1), along with downregulation of anticoagulant proteins (PROS1, SERPINA10). SVT patients showed heightened complement activation, markedly increased C7, VCAM1, and von Willebrand factor, and reduced levels of coagulation factors (F9, F10, F11). Hierarchical clustering and pathway enrichment analyses highlighted the central role of complement activation, platelet activation, and endothelial dysfunction in SVT pathogenesis. Serum validation confirmed elevated alternative pathway markers (Ba, Bb) and terminal complement products (C5a, sC5b-9) in SVT, implicating complement activation as a key driver of thrombosis. INTERPRETATION: This study identifies complement activation as a potential key contributor to thrombosis in JAK2V617F MPN patients, particularly those with SVT. The interplay between complement, coagulation, and endothelial dysfunction suggests potential therapeutic targets for reducing thrombotic complications in this high-risk population. FUNDING: This work was supported by AGAUR, ISCIII, and Novartis.
Sandwich immunoassay for evaluation of serum Kita-Kyushu Lung Cancer Antigen-1 as a potential diagnostic biomarker for gastric cancer.
Chen T, Li L, Cao X … +3 more , Wang Y, Liu Q, Liu B
Transl Oncol · 2025 Dec · PMID 41082823 · Full text
BACKGROUND: Kita-Kyushu Lung Cancer Antigen-1 (KK-LC-1) has been proved to be highly expressed in gastric cancer. Nevertheless, no studies have yet investigated the expression levels of KK-LC-1 in the serum of patients w...
BACKGROUND: Kita-Kyushu Lung Cancer Antigen-1 (KK-LC-1) has been proved to be highly expressed in gastric cancer. Nevertheless, no studies have yet investigated the expression levels of KK-LC-1 in the serum of patients with gastric cancer, its diagnostic potential, or its association with immune infiltration. METHODS: Designed Ankyrin Repeat Proteins (DARPins) that specifically target KK-LC-1 were identified through phage display screening. A method for quantifying KK-LC-1 concentration utilizing these DARPins was developed based on the sandwich immunoassay technique, and this method was employed to assess the expression levels of KK-LC-1 in serum samples from both gastric cancer patients and healthy donors. RESULTS: We found that compared to healthy donors, serum levels of KK-LC-1 were significantly elevated in gastric cancer patients and demonstrated a positive correlation with TNM stage, distant metastasis, conventional biomarkers, and tissue expression levels of KK-LC-1. Additionally, the expression levels of KK-LC-1 exhibited a negative correlation with the infiltration of various immune cell types. Furthermore, we have successfully developed a method for quantifying the concentration of KK-LC-1 protein and established a linear standard curve. CONCLUSIONS: KK-LC-1 has the potential to serve as a valuable diagnostic biomarker for gastric cancer and is correlated with immune cell infiltration.
Predicting ovarian cancer prognosis and immunotherapy response through siglec15 and PD-L1 expression analysis.
Zhao A, Hu S, Qiu Y … +2 more , Zhang P, Xu T
Transl Oncol · 2025 Dec · PMID 41076961 · Full text
BACKGROUND: Ovarian cancer (OC) is a highly aggressive malignancy often diagnosed in advanced stages. This study investigates the expression patterns and prognostic significance of Siglec15 and PD-L1 in OC, with the aim...
BACKGROUND: Ovarian cancer (OC) is a highly aggressive malignancy often diagnosed in advanced stages. This study investigates the expression patterns and prognostic significance of Siglec15 and PD-L1 in OC, with the aim of developing a novel prognostic tool and exploring potential targets for treatment. METHODS: Patients with OC were categorized into subgroups for analysis of tumor microenvironment and immune cell infiltration using the ESTIMATE and CIBERSORT algorithms. Predictive algorithms, including TIDE and IPS scores, were utilized to assess immunotherapy response. Immunohistochemistry analysis of Siglec15 and PD-L1 expression in clinical samples was performed. Additionally, cell culture experiments with SKOV3 cells and qRT-PCR assays were conducted to evaluate gene expression and functional effects of PD-L1 knockdown. Migration and invasion assays were carried out to assess cellular behaviors. RESULTS: Our study identified a novel prognostic subgroup in OC characterized by low Siglec15 and high PD-L1 expression, exhibiting improved overall survival compared to other subgroups. Further analysis revealed that the Siglec15 PD-L1 subgroup displayed a significantly more active immune microenvironment, characterized by increased infiltration of effector T cells, including CD8 T cells, activated memory CD4 T cells, and follicular helper T cells. This subgroup also showed upregulation of immune-related pathways, suggesting a more active immune response. Our results indicated that the Siglec15 PD-L1 subgroup is more likely to exhibit a favorable response to immunotherapy. Moreover, in vitro studies demonstrated that suppressing PD-L1 expression in OC cells led to increased Siglec15 expression and inhibited cell migration and invasion, suggesting a potential regulatory role of PD-L1 on Siglec15 expression and OC cells progression. CONCLUSIONS: Our findings emphasize the importance of combining assessment of Siglec15 and PD-L1 expression in patient stratification and treatment decision-making for OC, particularly regarding immunotherapy.
Aspyre Lung enables robust variant calling in samples that fail next generation sequencing quality control.
Gray ER, Evans RT, Gillon-Zhang E … +17 more , Knudsen KE, von Bargen K, Brown JN, King C, Kiser C, Rossi MB, Davis D, Taylor ML, Clower J, Yang J, Taylor C, Osborne RJ, Gregg J, Balmforth BW, Snyder RW, Levin WJ, Shapiro E
Transl Oncol · 2025 Dec · PMID 41076960 · Full text
Molecular testing in non-small cell lung cancer (NSCLC) identifies patients likely to respond to targeted therapeutics. Panel-based testing often employs next-generation sequencing, but challenges include high sample fai...
Molecular testing in non-small cell lung cancer (NSCLC) identifies patients likely to respond to targeted therapeutics. Panel-based testing often employs next-generation sequencing, but challenges include high sample failure rates, quality control issues, high tissue requirements and long turnaround times. Significant proportions of patients do not receive appropriate targeted therapy, with inferior clinical outcomes. Aspyre Lung is a targeted genomic profiling assay for 114 actionable or prognostic genomic variants across 11 genes with a two-day turnaround time of specimen to result. We profiled 198 NSCLC patient tissue samples using Aspyre Lung and a next-generation sequencing- (NGS)-based assay. Cohort A comprised 107 samples that failed to inform due to NGS quality checks, and Cohort B 91 samples that underwent successful NGS testing. Results were compared, and discrepancies resolved by orthogonal methods. For Cohort A (NGS fails), 103 (96 %) passed Aspyre Lung quality control, successfully yielding genomic results, including 48 (47 %) samples with ≥ one variant. In Cohort B (NGS pass), all samples passed Aspyre quality control with 97 % concordance to NGS-based testing. Notably, 80 % EGFR variant-positive samples were stages I and II. Aspyre Lung profiled 96 % of samples where NGS-based methods failed, and uncovered variants in samples successfully tested by NGS and deemed negative. Aspyre Lung detected ALK and EGFR variants from patients with early-stage disease, demonstrating utility as a rapid screening assay prior to neoadjuvant immuno-chemotherapy consideration.
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