J Cancer [JOURNAL]
Sun
200 papers
Pan-cancer analysis reveals SGO1 as a potential cancer prognostic and immunological biomarker.
Wang Y, Long X, Zhang L … +2 more , Zhou F, Zhong M
J Cancer · 2025 · PMID 40861810 · Full text
Shugoshin 1 (SGO1) is primarily known for its critical functions in chromosome segregation during cell division, protecting cohesin complexes and ensuring accurate mitotic processes. Previous studies have reported SGO1's...
Shugoshin 1 (SGO1) is primarily known for its critical functions in chromosome segregation during cell division, protecting cohesin complexes and ensuring accurate mitotic processes. Previous studies have reported SGO1's regulatory roles in isolated cancer types, but its pan-cancer significance and underlying mechanisms remain undefined. This study systematically investigates SGO1 in 33 cancer types, integrating multi-omics analyses and functional validation to reveal its role as a pan-cancer biomarker and therapeutic target. Using TCGA, GEPIA2, and HPA databases, we found SGO1 was significantly overexpressed in 19 cancer types compared to normal tissues. High SGO1 expression correlated with poorer overall survival (OS) and disease-free survival (DFS) in more than 10 cancers, validated by Kaplan-Meier analysis. Genomic analysis revealed frequent SGO1 mutations and DNA methylation dysregulation, while immune profiling showed associations with immune cell infiltration (B cells, CD8+ T cells) and PD-1/PD-L1 checkpoint genes. Protein-protein interaction and enrichment analyses uncovered BUB1 as a key co-expressed gene, suggesting a role in spindle checkpoint regulation. Functional assays in breast cancer cell line MDA-MB-231 and lung cancer cell line A549 showed SGO1 knockdown inhibited proliferation, migration, and invasion, with xenograft models confirming reduced tumor growth. Our findings establish SGO1 as a novel pan-cancer biomarker, linking its expression to tumor progression, immune evasion, and genomic instability. This study bridges bioinformatics with functional validation, offering new mechanistic insights and therapeutic avenues for SGO1-driven cancers.
Risk of Bladder Cancer in Patients with Chronic Indwelling Catheters: A Real-World Data Analysis.
Tseng WH, Lee CH, Lin RJ … +6 more , Ho CH, Liu CL, Huang SK, Chiu AW, Li CF, Shiue YL
J Cancer · 2025 · PMID 40861809 · Full text
Bladder cancer is the second most common urological malignancy worldwide, with significant morbidity and mortality. This study investigates the association between chronic indwelling catheter (CIDC) use and bladder cance...
Bladder cancer is the second most common urological malignancy worldwide, with significant morbidity and mortality. This study investigates the association between chronic indwelling catheter (CIDC) use and bladder cancer risk, particularly in relation to comorbidities and complications. Taiwan's National Health Insurance Research Database between 2007 and 2018 was used in this study. Patients with CIDC were identified based on records of catheterization on more than six occasions and matched with two patients without CIDC by age, gender, and index date. The outcome, bladder cancer, was identified using ICD-O-3: C67. The incidence rate of bladder cancer was calculated as the number of bladder cancer cases divided by the total follow-up years during the study period. Cox hazards model was also used to adjust with potential confounding variables. A total of 72,971 CIDC patients and 145,942 matched controls were analyzed. The incidence rate of bladder cancer in the CIDC group was 213.29 per 100,000 person-years, significantly higher than 40.4 per 100,000 person-years in the control group with incidence rate ratio: 5.23 (95% CI: 4.60-5.94, p<.0001). After adjusting with confoundings, patients with CIDC show a 5.16-fold higher risk of bladder cancer compared to those without (95% CI, 4.35-6.13, p<.0001). Subgroup analysis revealed a stronger association in younger patients and females. CIDC-related complications, such as urinary tract stones and benign prostatic hyperplasia (BPH), further increased bladder cancer risk. Our findings suggest a strong association between CIDC use and increased risk of bladder cancer, especially among younger patients and those with urological complications such as BPH and urinary tract stones. Additionally, comorbidities including chronic kidney disease, hypertension, and chronic obstructive pulmonary disease may contribute to this elevated risk. Therefore, an integrated healthcare strategy, including monitoring of comorbidities and complications, early cancer detection, and regular risk assessment, is critical for physicians to effectively manage bladder cancer risk in this population.
A Promising Prognostic Signature Consisting of Fatty Acid Metabolism Genes based on Machine Learning Predicts Biochemical Recurrence and Aids ARSI Therapy in Prostate Cancer.
Wu Z, Deng Y, Feng Y … +12 more , Tan Z, Cai S, He H, Yin W, Li J, Tian W, Lu J, Xie W, Lin J, Ye J, Han Z, Zhong W
J Cancer · 2025 · PMID 40861808 · Full text
Fatty acid metabolism (FAM) is a crucial metabolic characteristic of tumor cells, playing a role in various pathological processes during tumor development. Till now, the prognostic role of FAM-related genes of prostate...
Fatty acid metabolism (FAM) is a crucial metabolic characteristic of tumor cells, playing a role in various pathological processes during tumor development. Till now, the prognostic role of FAM-related genes of prostate cancer (PCa) is far from fully investigation. The combinations of 10 machine learning algorithms were applied in this study. A reliable signature, FAM-related gene score (FAMRGs), was developed to predict the prognosis of patients with PCa. External data sets were used to verify the accuracy and robustness of the FAMRGs. Drug sensitivity analysis was used to predict the optimal drug for high-risk PCa patients. The underlying mechanism related to FAMRGs were investigated by functional enrichment analysis. A nomogram based on FAMRGs was developed for personalized prediction of patient prognosis. A stable FAMRGs was construced and validated in 6 independent cohorts. FAMRGs accurately divided PCa patients into low and high risk group. FAMRGs showed stronger predictive ability compared with published prognostic signatures for PCa. Also, the androgen receptor signaling inhibitors (ARSI) treatment response predictive ability of FAMRGs was identified. Five drugs that were most suitable for patients in the high risk group of FAMRGs were screened. It was shown that FAMRGs involved in cell cycle-related pathways. The novel nomogram showed precisely predictive ability for the outcomes of patients with PCa. The FAMRGs can accurately predict the prognosis of PCa patients and is expected to direct the clinical treatment for PCa.
Implication of CDKN2A in cuproptosis through defining cuproptosis-related gene signature in ovarian cancer.
Zhang B, Yang Z, Zheng Y … +5 more , He Y, Yan Y, Song J, Wang F, An R
J Cancer · 2025 · PMID 40861807 · Full text
Cuproptosis is a kind of programmed cell death in which copper reacts with the cycloaliphatic component of the tricarboxylic acid (TCA) cycle. In this study, we devised a predictive model and a theoretical framework to e...
Cuproptosis is a kind of programmed cell death in which copper reacts with the cycloaliphatic component of the tricarboxylic acid (TCA) cycle. In this study, we devised a predictive model and a theoretical framework to examine the variations in the expression of the cuproptosis-related genes (CRGs) in ovarian cancer. Through screening the 11 CRGs, all samples were segmented into two risk groups and a prognostic model was built. Among the 11 CRGs, 10 genes showed a significant relationship with survival probability, demonstrating the model had good prediction ability and high accuracy. Age and FIGO stage were discovered to be strongly correlated with patient survival time by means of univariate Cox regression analysis. The patients over 65 in FIGO stages IIIA-IV had an increased risk. The enrichment analysis showed that the main metabolic pathways were those related to drug metabolism, tissue development, tyrosine metabolism and retinol metabolism. The PPI networks revealed that CDKN2A was the key gene. Finally, the and functional assays demonstrated that cuproptosis induced by CuET agent treatment could significantly inhibit ovarian cancer cell viability, migration and invasion as well as xenografted tumor growth where the CDKN2A expression level increased. Our results indicate that the comprehensive definition of differentially expressed CRGs in ovarian cancer will provide new insights for clinical remedy of ovarian cancer.
Investigating the Role of Lactate-Related Genes in Radiotherapy Resistance of Lung Cancer by Integrated Bioinformatics and Experiment Validation.
Li Q, Shen L, Yang Y … +5 more , Tai G, Zhu Q, Liu C, Ge Q, Yi Q
J Cancer · 2025 · PMID 40861806 · Full text
Radiotherapy is a standard treatment for advanced lung cancer, but resistance remains a significant cause of treatment failure. This study aimed to investigate lactate-associated genes to identify patients likely to bene...
Radiotherapy is a standard treatment for advanced lung cancer, but resistance remains a significant cause of treatment failure. This study aimed to investigate lactate-associated genes to identify patients likely to benefit from radiotherapy. RNA-seq data from 99 patients with lung cancer who underwent radiotherapy were analyzed to identify differentially expressed genes (DEGs) between resistant and sensitive cases. Bioinformatics tools were used to assess the prognostic relevance of lactate-related genes, and a risk score model was develpoed based on these genes. Dysregulation of these genes in patients with lung cancer undergoing radiotherapy was validated through experiments. Molecular docking was used to explore potential radiosensitizers. The analysis identified 1482 DEGs, with enrichment analysis highlighting lactate metabolism pathways. A risk score model was constructed using the lactate-related genes ADAMTS3, FADS2, and RTBDN to classify patients into high- and low-risk subgroups. Functional enrichment analysis revealed the model's impact on DNA repair and tumor immunity. A nomogram was developed for clinical implementation. Wet lab experiments further confirmed these findings. In conclusion, a novel risk score model based on lactate-related genes was developed to predict radiotherapy outcomes in lung cancer. FADS2 was identified as a potential biomarker for predicting resistance to radiotherapy. This study is the first to examine the predictive value of lactate-related genes for radiotherapy efficacy in lung cancer, offering valuable insights for personalized treatment strategies to improve therapeutic outcomes.
HLA-DOB: A Key "Coordinator" Between Cutaneous Melanoma and Psoriasis.
Li Y, Luo J, Tian D … +8 more , Li C, Wu C, Wang G, Guo R, He L, Li L, Tian Y, Hu L
J Cancer · 2025 · PMID 40861805 · Full text
Psoriasis is a chronic inflammatory skin disease associated with immune dysfunction, and its relationship to cutaneous melanoma is unclear. This study used Mendelian randomization (MR) to explore the causal link between...
Psoriasis is a chronic inflammatory skin disease associated with immune dysfunction, and its relationship to cutaneous melanoma is unclear. This study used Mendelian randomization (MR) to explore the causal link between the two and identify risk genes. SNPs from a psoriasis GWAS (5,072 cases, 478,102 controls) were used as instrumental variables, and melanoma GWAS data (3,751 cases, 372,016 controls) served as the outcome. Causal relationships were assessed using IVW, MR-Egger, and weighted median methods, with sensitivity tests. Co-localization and transcriptome analyses identified risk genes. Forward MR showed psoriasis significantly reduced melanoma risk (PIVW=0.040). The co-localization analysis revealed genes positively associated with the risk of psoriasis, including HLA-DOB, NOTCH4, and VARS2. HLA-DOB was the only risk gene of psoriasis that showed differential expression in cutaneous melanoma based on transcriptional analysis. HLA-DOB was downregulated in melanoma and associated with better prognosis (P=0.033). Single-cell analysis showed that HLA-DOB was mainly enriched in B cells (especially memory B cells) and myeloid cells (particularly DC: monocyte-derived). Our findings suggest an inverse causal relationship between melanoma and psoriasis. Importantly, we also found that HLA-DOB can be served as a key "coordinator" between cutaneous melanoma and psoriasis: a risk gene of psoriasis and a protective factor of cutaneous melanoma.
Exploration of the relationship between apoptosis related characteristic genes and the prognosis of HCC.
Zhang Q, Cao Z, Cao H … +6 more , Wu H, Yan S, Kan Y, Cui X, Feng Y, Liu Z
J Cancer · 2025 · PMID 40861804 · Full text
The acquisition of resistance to anoikis is a critical driver of metastasis in various tumor types. However, the combined role of anoikis apoptosis in the progression and prognosis of hepatocellular carcinoma (HCC) remai...
The acquisition of resistance to anoikis is a critical driver of metastasis in various tumor types. However, the combined role of anoikis apoptosis in the progression and prognosis of hepatocellular carcinoma (HCC) remains largely unexplored. This study integrates known anoikis genes with single-cell datasets to identify differentially expressed Anoikis (DE-Anoikis) through unsupervised clustering, enabling the classification of samples from The Cancer Genome Atlas (TCGA). A prognostic risk model was constructed using univariate Cox proportional hazards regression and validated with external datasets from the International Cancer Genome Consortium (ICGC) and the Gene Expression Omnibus (GEO). The results revealed significant prognostic differences among DE-Anoikis-based HCC molecular subtypes, with functional enrichment analyses highlighting metabolic reprogramming differences. Furthermore, the anoikis-related prognostic model demonstrated robust predictive accuracy across multiple validation datasets. Two potential therapeutic drugs exhibited sensitivity in low-risk patients, offering novel insights into HCC treatment. Overall, this study identifies a unique subgroup of apoptosis-associated HCC and a prognostic model, providing further biological insights into the molecular mechanisms and therapeutic strategies for HCC.
DUSP9 is Up-Regulated and Promotes Tumor Progression in Head and Neck Squamous Cell Carcinoma.
Hu Y, Li Y, Jiang C … +4 more , Han W, Chen X, Wang P, Xu H
J Cancer · 2025 · PMID 40861803 · Full text
Head and neck squamous cell carcinoma (HNSCC) ranks among the most prevalent malignancies with a poor prognosis. The underlying mechanisms driving HNSCC carcinogenesis are not fully elucidated. In this study, we identifi...
Head and neck squamous cell carcinoma (HNSCC) ranks among the most prevalent malignancies with a poor prognosis. The underlying mechanisms driving HNSCC carcinogenesis are not fully elucidated. In this study, we identified dual specificity phosphatase 9 (DUSP9) as a carcinogenic factor in HNSCC development. According to the public data, DUSP9 was significantly up-regulated in HNSCC tumor tissues compared to normal tissues, confirmed by clinical data and single-cell RNA sequencing (scRNA-seq) data. Survival analysis revealed that high levels of DUSP9 expression contribute to poor prognosis in HNSCC patients. Knockdown of DUSP9 decreased, but overexpression of DUSP9 increased the proliferation and migration of HNSCC cells. ScRNA-seq data analysis suggested that DUSP9 was selectively expressed in tumor cells, with negligible expression in immune cells and stromal cells, and showed an elevated trend from primary tissues to metastatic tissues. Enrichment analyses of DUSP9-correlated genes suggested the involvement of DUSP9 in cell adhesion, wound healing, cell migration, transcription regulation and metabolic process. Furthermore, DUSP9 expression in tumor tissues exhibited an inverse relationship with immune cell infiltration within the tumor microenvironment (TME). In conclusion, this study provided evidence that DUSP9 was up-regulated in HNSCC tissues and may play a pivotal role in HNSCC progression, suggesting its potential as a novel biomarker.
Integrating Bulk RNA and Single-cell transcriptome to explore the role of glycan-related genes in lung adenocarcinoma.
Zhu K, Yang C, Wang G … +6 more , Wang X, Lin C, Li Y, He N, Tian Y, Shen W
J Cancer · 2025 · PMID 40861802 · Full text
Despite significant advancements in the diagnosis and therapeutic management of lung adenocarcinoma (LUAD), patient outcomes continue to be suboptimal, primarily attributable to the intricate of the tumor microenvironmen...
Despite significant advancements in the diagnosis and therapeutic management of lung adenocarcinoma (LUAD), patient outcomes continue to be suboptimal, primarily attributable to the intricate of the tumor microenvironment (TME). Recently, attention has been paid to the role of glycans and their glycosylation modifications in tumor progression. In the present investigation, we performed analyses to identify 13 glycan-related genes with prognostic significance in LUAD. High- and low-risk groups were distinguished by a constructed model of glycan-related genes. Single-cell analysis was performed to investigate the TME in LUAD. Drug screening analysis was utilized to predict potential candidate drugs. High-risk patients exhibited aggressive tumor progression. Further single-cell analysis revealed that tumor cells expressing high-risk glycan-related genes displayed enhanced interactions with immune and stromal cells, suggesting that aberrant glycosylation and glycan biosynthesis may contribute to worse outcomes in LUAD by promoting immune suppression. Furthermore, based on the molecular characteristics, we identified several potential candidate drugs for personalized treatment, including docetaxel, alpelisib, and gefitinib. Our study found that glycan-related genes could alter the composition of immune cell infiltration in LUAD tumor tissues and might affect the interaction between immune cells and tumor cells through intercellular section signals, resulting in the inability of immune cells to normally initiate immune responses against tumor cells. These findings offer new biological perspectives of glycan-related genes in shaping the TME and potential targets for personalized LUAD treatment.
Strategies to Overcome PD-1/PD-L1 Blockade Resistance: Focusing on Combination with Immune Checkpoint Blockades.
Liu D, Xiao H, Xiang Y … +4 more , Zhong D, Liu Y, Wang Y, Zhang W
J Cancer · 2025 · PMID 40861801 · Full text
In recent years, immune checkpoint blockades (ICBs) have made rapid progress in the field of cancer treatment, providing significant therapeutic effects and survival benefits, especially in patients with advanced refract...
In recent years, immune checkpoint blockades (ICBs) have made rapid progress in the field of cancer treatment, providing significant therapeutic effects and survival benefits, especially in patients with advanced refractory tumors. PD-1/PD-L1 blockade is one of the most widely used ICBs. However, its application is limited by low response rate and drug resistance. It is of great significance to investigate the complex mechanisms of PD-1/PD-L1 blockade resistance. In this review, we outline some crucial aspects, including lack of effector T cells, lack of target PD-1/PD-L1, poor immunogenicity of tumors, immunosuppressive TME, and other mechanisms (such as metabolism, epigenetic alterations, and gut microbiota). Combination therapy has become a promising strategy to overcome drug resistance. Based on the upregulation of other immune checkpoints after PD-1/PD-L1 blockade treatment, we focus on the combination with other ICBs, including CTLA-4, TIM-3, LAG-3, TIGIT, VISTA, and some emerging immune checkpoints, so as to provide evidence for improving the benefit of ICBs in cancers.
Nit1 is upregulated in non-small cell lung cancer and promotes cancer cell proliferation and invasion and regulates EMT-related molecules and cyclins.
Wang J, Jiang B, Wang X … +2 more , Liu H, Fan C
J Cancer · 2025 · PMID 40740246 · Full text
Nitrilase homolog 1 (Nit1) is a member of the carbon-nitrogen hydrolase family whose function in human cancer is largely unknown. In this study we investigated the expression and function of Nit1 in non-small cell lung c...
Nitrilase homolog 1 (Nit1) is a member of the carbon-nitrogen hydrolase family whose function in human cancer is largely unknown. In this study we investigated the expression and function of Nit1 in non-small cell lung cancer (NSCLC) and vitro. Immunohistochemistry study shows that expression of Nit1 was elevated in non-small cell lung cancer compared to normal lung epithelial cells including submucosal glands and bronchial epithelial cells (p<0.05). Expression of Nit1 was significantly associated with advanced TNM stages, lymph node metastasis and poor clinical outcome of the patients (60.70 ±5.48 vs 30.83 ± 4.88) (p<0.05). Western blot also shows elevated expression of Nit1 in cancer tissues compared to adjacent normal lung tissues (p<0.05). We detected Nit1 expression using Western blot in lung cancer cell lines including A549, H460, H661, H1299, LK2, PC9, and SK, and bronchial epithelial cell line HBE. Immunofluorescent staining shows that Nit1 was located in cytoplasm in HBE, A549, H1299, H460 and PC9 cells. Overexpression of Nit1 in H1299 cells significantly promoted cancer cell proliferation and invasion (p<0.05). Western blot study confirmed that overexpression of Nit1 in H1299 cells significantly upregulated EMT-related molecules including MMP3, Slug, snail, and cyclins including cyclin D1, cyclin D3 and cyclin E, and downregulated EMT-related molecule E-cadherin. These results indicate that Nit1 expression was upregulated in non-small cell lung cancer and may contribute to the malignant phenotype through regulating EMT-related molecules and cyclins.
Impact of PIK3CA Mutations on the Clinical Benefits of CDK 4/6 Inhibitors in HR+/HER2- Advanced Breast Cancer: An Updated Pairwise and Network Meta-Analysis.
Wang SF, Chou CY, Chao YW … +9 more , Chan TK, Yeh WY, Chiang CE, Chen CH, Lee HC, Tseng LM, Chang YL, Cheng HM, Liu CY
J Cancer · 2025 · PMID 40740245 · Full text
Cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) have revolutionized the treatment of hormone receptor-positive (HR+) and human epidermal growth factor receptor-2 negative (HER2-) advanced breast cancer. However, identif...
Cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) have revolutionized the treatment of hormone receptor-positive (HR+) and human epidermal growth factor receptor-2 negative (HER2-) advanced breast cancer. However, identifying reliable biomarkers and determining overall survival (OS) outcomes for CDK4/6i remains challenging. We conducted a systematic review and updated pairwise meta-analysis of randomized controlled trials to evaluate the clinical benefits and biomarker interactions of CDK4/6i in HR+ and HER2- advanced breast cancer. Hazard ratio (HR) and 95% confidence interval (CI) were calculated for progression-free survival (PFS) and OS across different clinical settings. Additionally, a network meta-analysis was performed to assess the comparative efficacy of different CDK4/6i in specific populations using ranking probabilities. CDK4/6i significantly improved PFS (HR 0.55, 95% CI 0.52-0.59) and OS (HR 0.80, 95% CI 0.74-0.86) in patients with HR+/HER2- advanced breast cancer. Sensitivity analyses confirmed the robustness of these findings. Subgroup and meta-regression analyses demonstrated consistent clinical benefits across different lines of therapy, endocrine therapy categories, patient characteristics, and follow-up durations. However, mutation status emerged as a potential CDK4/6i efficacy modifier, particularly among patients who were endocrine therapy-naïve for advanced disease (First-line treatment: for interaction = 0.03; received prior treatment, = 0.68). The network meta-analysis suggested comparable overall efficacy among CDK4/6i. However, ribociclib may offer a slight OS advantage over palbociclib in first-line treatment, with ranking probabilities varying by specific clinical settings. This updated meta-analysis further validates the OS benefit of CDK4/6i in HR+/HER2- advanced breast cancer. The influence of mutation status on CDK4/6i efficacy appears more pronounced in endocrine therapy-naïve patients rather than those receiving later-line therapy. While currently approved CDK4/6 inhibitors exhibit similar efficacy overall, their ranking probabilities vary depending on individual clinical contexts. These findings highlight the need for further investigation into the modifying effects of status and specific CDK4/6i to optimize treatment strategies in HR+/HER2- advanced breast cancer.
Differential diagnosis of benign and malignant ovarian tumors with combined tumor and systemic inflammation-related markers.
Song D, Liu T, Han C … +2 more , Zhang C, Kong W
J Cancer · 2025 · PMID 40740244 · Full text
To explore the diagnostic significance of pre-surgery peripheral blood tumor markers cancer antigen 125 (CA125) and human epitope protein 4 (HE4), in conjunction with neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lym...
To explore the diagnostic significance of pre-surgery peripheral blood tumor markers cancer antigen 125 (CA125) and human epitope protein 4 (HE4), in conjunction with neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), platelet count-to-lymphocyte ratio (PLR), and systemic immunoinflammatory index (SII), in the differential diagnosis of epithelial ovarian cancer (EOC) and benign ovarian tumors. Determine the best combination of diagnostic indicators for early diagnosis of EOC. We retrospectively analyzed clinical data from 189 patients with EOC and 202 patients with benign ovarian tumors, comparing levels of CA125, HE4, and inflammatory markers, and evaluated the efficacy of these markers in diagnosing EOC alone or in combination by calculating sensitivity, specificity, and receiver operating characteristic curve (ROC). Serum concentrations of CA125, HE4, NLR, PLR, MLR, and SII were significantly higher in the EOC group than in the benign ovarian tumor group (P < 0.001). In 189 cases of EOC, CA125 and HE4 were significantly higher in advanced stages than in early stages (P = 0.000, P = 0.012). NLR, PLR, MLR, and SII showed no significant difference between early and advanced stages (P>0.05), and this was also the case in 141 patients with high-grade serous ovarian cancer. CA125, HE4, NLR, PLR, MLR, and SII showed no significant differences across age groups, menopausal states, or pathological types (P > 0.05 for all). For diagnosing EOC, both the CA125+HE4+NLR+PLR+MLR+SII and CA125+HE4+PLR+MLR+SII models achieved the highest AUC values (AUC = 0.951 for both). No statistically significant difference was observed between these two models in AUC comparison (P=0.9305). NLR alone showed the lowest AUC at 0.696. The CA125+HE4+PLR+MLR+SII model demonstrated the highest sensitivity (84.66%), while CA125+HE4 showed the highest specificity (95.54%). Preoperative peripheral blood tumor markers combined with inflammatory markers can improve the diagnostic efficiency of EOC. Among these combinations, CA125+HE4+PLR+MLR+SII demonstrated optimal diagnostic performance with the highest efficacy and sensitivity, providing a clinical basis for enhanced EOC diagnosis.
The Traditional Chinese Medicine Formula Induces Cell Cycle Arrest and Apoptosis through Restoration of Retinoblastoma Protein Function and Inhibition of Aurora Kinase Activity.
Chang CJ, Wu CC, Hsieh YJ … +6 more , Chen JK, Kung YL, Tsai WT, Huang HS, Lin SZ, Ho TJ
J Cancer · 2025 · PMID 40740243 · Full text
Traditional Chinese Medicine (TCM) has a long-standing history in treating various diseases, including cancer. Wu Bao San is a traditional formula known for its ability to clear heat, detoxify, relieve cough and phlegm a...
Traditional Chinese Medicine (TCM) has a long-standing history in treating various diseases, including cancer. Wu Bao San is a traditional formula known for its ability to clear heat, detoxify, relieve cough and phlegm and treat tumours. The modified Wu Bao San (MWBS) is a conventional medicine prescribed by doctors of Chinese medicine. However, the molecular mechanisms underlying the anticancer effects remain unclear owing to the complexity of the components of traditional Chinese medicine, making it challenging to pinpoint specific molecular targets or pathways underlying their clinical effect. In this study, we used an MTT assay, flow cytometry, indirect immunofluoresence imaging, and western blotting to analyse the viability, cell cycle profiles, morphology, and protein levels of cells after MWBSE treatment. Our results showed that MWBSE has multiple anticancer effects. First, MWBSE induces cytokinesis failure by inhibiting Aurora kinase, leading cells to commit to cell death. Additionally, MWBSE reduces the phosphorylation of Rb, restoring its function and resulting in cell cycle arrest. The overexpression of Aurora kinases plays a pivotal role in sustaining malignant cell behaviors such as uncontrolled growth, colony formation, and tumor development. The retinoblastoma protein (Rb) is a key tumor suppressor that regulates the cell cycle, particularly the transition from the G1 to the S phase due to its significant involvement in tumor biology. Aurora kinases and Rb have emerged as promising targets for cancer therapy. Our findings provide a mechanistic explanation of the targets and anti-tumor pathways of MWBSE.
Predictive and Prognostic Biomarkers of Recurrence in Locoregional Colorectal Cancer.
Cendra AS, Pekarek L, Ospino LR … +18 more , Dbouk Y, Chnaiker S, Luengo A, Villamor T, Corralo A, Pedrejon B, Pekarek T, Barrena-Blázquez S, Díaz-Pérez D, Minaya-Bravo AM, López-Gonzalez L, Alonso MD, Giménez TR, Gutiérrez-Calvo A, Álvarez-Mon M, Espinosa JC, Díaz-Pedrero R, Ortega MA
J Cancer · 2025 · PMID 40740242 · Full text
Colorectal cancer (CRC) remains a major global health challenge, as recurrence and metastasis continue to significantly impact patient survival and management, especially in cases of locoregional disease. In this regard,...
Colorectal cancer (CRC) remains a major global health challenge, as recurrence and metastasis continue to significantly impact patient survival and management, especially in cases of locoregional disease. In this regard, identifying reliable predictive and prognostic biomarkers is essential not only for improving therapeutic strategies but also for personalizing treatment plans and guiding post-treatment surveillance. This article comprehensively reviews histological, genetic, microRNA (miRNA), circulating tumor cell (CTC), and serological biomarkers, all of which are closely linked to recurrence and metastatic progression in locoregional CRC.On the one hand, histological markers, such as tumor budding and lymphovascular invasion, offer crucial prognostic insights regarding disease aggressiveness. On the other hand, genetic alterations, including mutations in KRAS, BRAF, and TP53 genes, serve as predictive indicators for therapeutic response as well as risk of recurrence. Moreover, specific miRNAs, such as miR-21, have emerged not only as diagnostic but also as prognostic tools due to their association with metastasis and chemoresistance. Furthermore, circulating tumor cells and cell-free DNA (cfDNA) released by tumors into the bloodstream represent non-invasive biomarkers that are useful for the early detection of micrometastatic disease and real-time monitoring of therapeutic efficacy. Additionally, serological markers, including carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA 19-9), continue to play key roles in the routine surveillance of CRC. Integrating these biomarkers into clinical practice thus holds significant potential to stratify patients at high risk of recurrence and guide personalized therapeutic approaches, ultimately improving outcomes for CRC patients. This review consolidates recent findings and underscores the ongoing need for further studies to validate these biomarkers across larger patient cohorts and various CRC stages.
Pembrolizumab versus Pembrolizumab plus Chemotherapy in Non-small Cell Lung Cancer with High PD-L1 Expression - Multicenter Real-world Evidence Study.
Svaton M, Knetki-Wroblewska M, Hosek P … +6 more , Chowaniecova G, Spacek J, Fischer O, Bilek O, Hrnciarik M, Kauffmann-Guerrero D
J Cancer · 2025 · PMID 40740241 · Full text
Patients with non-small cell lung cancer (NSCLC) with PD-L1 expression ≥ 50% can be treated with immunotherapy alone or with a combination of immunotherapy and chemotherapy. One of these options is treatment with pembrol...
Patients with non-small cell lung cancer (NSCLC) with PD-L1 expression ≥ 50% can be treated with immunotherapy alone or with a combination of immunotherapy and chemotherapy. One of these options is treatment with pembrolizumab (P) with/without chemotherapy (CHT). Meta-analyses from randomized trials suggest a beneficial effect on response rate (RR) or progression free survival (PFS) when using the combination treatment P + CHT compared to P alone, but not on improving overall survival (OS). However, data from real-world clinical practice are insufficient especially in European patients. Regional differences, e.g. in the representation of KRAS mutations between Asian and European patients, could theoretically influence potential differences between P + CHT and P. Therefore, the aim of this study was to compare P + CHT versus P alone in real clinical practice in patients from Central Europe. Retrospective data from 8 comprehensive oncology centres in Central Europe were used. All patients with PD-L1 expression ≥ 50% with stage IV NSCLC treated with pembrolizumab in daily practice to June 2024 were included and their data statistically analysed. In the whole group 793 patients was included in the study - 706 treated with P and 87 with P+ CHT. In this unadjusted sample, we observed significantly higher RR (p <0.0001) and OS (p = 0.044) for the P + CHT group vs. P. For significant differences in both groups, where performance status in particular played a role in survival in the Cox model, we subsequently performed patient matching 2 (P+CHT):1 (P) from the whole group of patients. After this patient matching, we continued to observe a significant difference in RR (p = 0.005), but no longer in OS (p = 0.103). The PFS was not significantly different in both cases (p= 0.174 for unadjusted patients resp. p = 0.342 for matching groups). P+CHT leads to a significantly higher RR compared to P and can therefore be considered in patients with a more certain treatment response goal (e.g., bulky symptomatic tumor), however, this advantage does not translate into PFS and OS benefit.
Comprehensive Mendelian randomization and colocalization analysis of plasma proteomics to identify new therapeutic targets for bladder cancer.
Zuo J, Chen J, Tan Z … +6 more , Wen L, Zhao J, Fu Y, Wang H, Fu S, Wang J
J Cancer · 2025 · PMID 40740240 · Full text
Bladder cancer is characterized by a high recurrence rate and aggressive behavior, with frequent emergence of chemoresistance. Current treatments such as surgery, chemotherapy, and immunotherapy have limited efficacy, un...
Bladder cancer is characterized by a high recurrence rate and aggressive behavior, with frequent emergence of chemoresistance. Current treatments such as surgery, chemotherapy, and immunotherapy have limited efficacy, underscoring the urgent need for effective early diagnostic biomarkers and novel targeted therapies. In this study, we integrated plasma proteomic data from the UK Biobank Pharma Proteomics Project (UKB-PPP) and the Icelandic deCODE study with genome-wide association study (GWAS) data. We employed two-sample Mendelian randomization (MR), Bayesian colocalization analysis, and SMR/HEIDI tests to systematically identify potential plasma protein targets associated with bladder cancer risk. A total of 199 plasma proteins were found to be significantly associated with bladder cancer risk, among which five proteins (SLURP1, LY6D, WFDC1, NOV, and GSTM3) emerged as core candidate targets. Further validation showed that NOV and GSTM3 demonstrated robust causal associations with bladder cancer across multiple analytical methods, and molecular docking analysis revealed that these two proteins can bind to estrogen/progestin hormone-regulating drugs. Our study identified multiple plasma proteins with causal links to bladder cancer and revealed their potential roles in tumor immune evasion, antioxidant defenses, and tumor metabolism. These findings provide new insights into bladder cancer biology and offer potential targets for precision therapy and drug repositioning.
Neuregulin-1 correlates to early castration-resistant prostate cancer after prostate cancer patients receiving androgen deprivation therapy.
Li S, Zhao W, Wang D … +3 more , Chen L, Feng Y, Sun P
J Cancer · 2025 · PMID 40740239 · Full text
Neuregulin-1 (NRG1) levels were elevated in prostate cancer patients receiving androgen deprivation therapy (ADT). However, it remains unclear whether NRG1 levels could predict castration-resistant prostate cancer (CRPC)...
Neuregulin-1 (NRG1) levels were elevated in prostate cancer patients receiving androgen deprivation therapy (ADT). However, it remains unclear whether NRG1 levels could predict castration-resistant prostate cancer (CRPC) progression. Prostate cancer patients were divided into CRPC and NCRPC (non-CRPC) groups. Baseline clinicopathological characteristics and prostate-specific antigen (PSA) levels were compared among two groups. Subsequently, the levels of NRG1 in blood and tumor tissue were detected using enzyme-linked immunosorbent assay, western blotting, and qPCR. The predictive value of NRG1 was evaluated using receiver operating characteristic (ROC) analysis. Meanwhile, the correlation of NRG1 with Gleason score and PSA levels was analyzed using Spearman analysis. The comparison analysis showed that TNM classification, Gleason scores, and PSA levels were significantly correlated to CRPC. Moreover, the serum NRG1 and the protein and mRNA levels of NRG1 were higher in CRPC patients than in NCRPC patients. ROC analysis unveiled that NRG1 levels in the patients before ADT could predict CRPC progression. Moreover, Spearman analysis also showed that NRG1 was correlated to Gleason scores and PSA levels. Serum NRG1, NRG1 protein, and NRG1 mRNA in tumor tissue from prostate cancer patients before ADT could predict the incidence of CRPC in patients receiving ADT.
Study on the mechanism of gracillin inhibiting the of lung cancer NCI-H1299 cells based on MAPK signaling pathway.
Xiao B, Zhang M, Liu H … +8 more , Cui A, Tian Y, Tang F, Liao S, Li M, Huang H, Peng W, Yang J
J Cancer · 2025 · PMID 40740238 · Full text
In this study, we investigated the potential of gracillin, a steroidal saponin compound, as an anticancer agent against non-small cell lung cancer (NSCLC) and explored its impact on autophagy mechanisms. Gracillin signif...
In this study, we investigated the potential of gracillin, a steroidal saponin compound, as an anticancer agent against non-small cell lung cancer (NSCLC) and explored its impact on autophagy mechanisms. Gracillin significantly inhibited NCI-H1299 cell proliferation and induced autophagic cell death. Mechanistically, gracillin activated the MAPK signaling pathway, evidenced by increased p-ERK and decreased p-JNK levels, suggesting their roles in mediating autophagy induction. Additionally, gracillin upregulated WIPI1 expression, a key autophagy-related protein potentially downstream of the ERK pathway. Evaluation in a xenograft mouse model demonstrated robust anticancer efficacy of gracillin with no significant adverse effects observed. These findings highlight gracillin as a promising candidate for NSCLC therapy, leveraging its ability to induce autophagy through MAPK pathway modulation. Our study provides valuable insights into the therapeutic potential of gracillin and supports its further development as a safe and effective treatment option for NSCLC.
Hypoxia upregulate TPM4 expression to strengthen epithelial-mesenchymal transition that promotes lymph node metastasis of papillary thyroid cancer.
Li Z, Li F, Jiang X … +10 more , Li Y, Jia L, Wang X, Liu Y, Jiang R, Zhao K, Pu G, Tian Y, Wang Y, He X
J Cancer · 2025 · PMID 40740237 · Full text
Papillary thyroid cancer (PTC) exhibits a high propensity for lymph node metastasis (LNM), significantly impacting postoperative recurrence and patient prognosis. The hypoxic microenvironment critically drives tumor prog...
Papillary thyroid cancer (PTC) exhibits a high propensity for lymph node metastasis (LNM), significantly impacting postoperative recurrence and patient prognosis. The hypoxic microenvironment critically drives tumor progression by promoting PTC dedifferentiation. Through integrated bioinformatics analysis combining weighted gene co-expression network analysis and machine learning approaches on TCGA data, we identified TPM4 as a key hypoxia-responsive gene in PTC and validated its association with LNM using GEO datasets. Gene set enrichment analysis demonstrated that patients with high TPM4 expression in both TCGA and GEO databases showed significant enrichment in hypoxia and epithelial-mesenchymal transition (EMT) pathways. Single-cell pseudotime analysis revealed concurrent increases in hypoxia pathway enrichment, TPM4 expression, and EMT pathway activation during cell differentiation. Experimental validation using RT-qPCR and Western blot analyses confirmed that hypoxia-induced TPM4 upregulation activated EMT signaling. Functional assays demonstrated that TPM4 enhanced cellular invasion and migration capabilities. Our findings illuminate a novel mechanism whereby the hypoxic tumor microenvironment promotes lymph node metastasis in PTC through TPM4-mediated activation of EMT signaling, providing new insights into LNM of PTC.
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