Cancer Cell International最新文献

{"title":"Overexpressed NEK2 contributes to progression and cisplatin resistance through activating the Wnt/β-catenin signaling pathway in cervical cancer.","authors":"Jiang Haiye, Wang Xiangzhu, Zhang Yunfei, Gui Shumin, Ni Chang, Jiang Yaohui, Yin Heng, Nie Xinmin","doi":"10.1186/s12935-025-03644-x","DOIUrl":"10.1186/s12935-025-03644-x","url":null,"abstract":"<p><strong>Background: </strong>Cervical cancer ranks as the fourth most common cancer among women, with cisplatin resistance posing a significant challenge to the long-term survival of patients.</p><p><strong>Methods: </strong>The roles of NEK2 in cervical cancer were examined through bioinformatics analysis. Transfection efficiency and molecular mechanisms were assessed using real-time quantitative polymerase chain reaction (qRT-PCR) and western blotting (WB). To evaluate cell functions, a series of assays, including cell counting kit-8 (CCK-8), wound healing, transwell, colony formation, and flow cytometry (FCM), were performed on HeLa, SiHa, and HeLa/DDP (cisplatin-resistant) cell lines.</p><p><strong>Results: </strong>We found that NEK2 is upregulated in cervical cancer tissues compared to normal tissues and is further elevated in cisplatin-resistant cervical cancer compared to cisplatin-sensitive cases. The overexpression of NEK2 is associated with enhanced cancer progression, poorer prognosis, and increased cisplatin resistance in cervical cancer patients. Notably, in the presence of cisplatin, the knockdown of NEK2 inhibited cell viability, proliferation, migration, invasion, and G2/M phase arrest in cervical cancer cells, while also enhancing the sensitivity of cisplatin-resistant cervical cancer cells through the inactivation of the Wnt/β-catenin signaling pathway.</p><p><strong>Conclusions: </strong>NEK2 is upregulated in cervical squamous cell carcinoma (CESC) compared to normal tissues and exhibits higher levels in cisplatin-resistant CESC than in sensitive counterparts, correlating with disease progression and poor prognosis. Thus, NEK2 is implicated in the cisplatin resistance of CESC via the activation of the Wnt/β-catenin signaling pathway, suggesting its potential as a prognostic marker and a novel target for the diagnosis and treatment of cisplatin-resistant CESC.</p>","PeriodicalId":9385,"journal":{"name":"Cancer Cell International","volume":"25 1","pages":"45"},"PeriodicalIF":5.3,"publicationDate":"2025-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11829479/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143425092","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An online clustering algorithm predicting model for prostate cancer based on PHI-related variables and PI-RADS in different PSA populations.","authors":"Jiyuan Hu, Qi Miao, Jiayi Ren, Hongbo Su, Xianlu Zhang, Jianbin Bi, Gejun Zhang","doi":"10.1186/s12935-025-03677-2","DOIUrl":"10.1186/s12935-025-03677-2","url":null,"abstract":"<p><strong>Background and aim: </strong>Prostate cancer is the most common male malignancy. Current diagnostic methods using single TPSA and PHI lack specificity. Some researches have created nomograms for predicting risk, but these are not easily visualized. Our study aims to find the best negative predictive value (NPV) for PHI, then build a clustering model to display prostate cancer risk categories, particularly useful for patients with PSA > 20 and be actually applied in clinical work.</p><p><strong>Method: </strong>We collected 708 patients in the training cohort and 143 in the validation cohort, divided into three groups based on their PSA levels. Next, we determined optimal and customized PHI cut-off values, calculated NPV and PPV, and selected logistic regression as the best method among several machine-learning algorithms. Subsequently, the significant variables were identified, and then a clustering algorithm was constructed. Finally, the model was validated and made available online for further clinical application.</p><p><strong>Results: </strong>The Optimal PHI cut-off lower limits for PSA > 4, PSA4-20, PSA > 20 subgroups were 23.85, 24.35, and 40.75, with upper limits of 142.9, 143, and 135.6, respectively. The clustering model of the optimal cohort for PSA > 4 and PSA 4-20 sub-groups showed a superior Silhouette coefficients of 0.433 and 0.526 than that of the customized PHI cohort (0.432, 0.452). The PSA > 20 subgroup owned the highest Silhouette coefficient of 0.572. The validation cohort showed AUC values of 0.761, 0.823, 0.833 for these 3 sub-groups, with accuracy rates of 88.81%, 90.38%, and 82.05%.</p><p><strong>Conclusion: </strong>In conclusion, our clustering model effectively categorizes patients into distinct risk groups with clear visualization and has demonstrated stability and reliability in the validation cohort, potentially aiding in early diagnosis of prostate cancer in clinical practice.</p>","PeriodicalId":9385,"journal":{"name":"Cancer Cell International","volume":"25 1","pages":"44"},"PeriodicalIF":5.3,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11827463/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143413495","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Arcyriaflavin A, a cyclin D1/CDK4 inhibitor, suppresses tumor growth, migration, and invasion of metastatic melanoma cells.","authors":"Dokyeong Kim, Junseong Park, Yoon-Seob Kim, Okcho Na, Minyoung Park, Songzi Zhang, Sumin Cho, Yeun-Jun Chung","doi":"10.1186/s12935-025-03675-4","DOIUrl":"10.1186/s12935-025-03675-4","url":null,"abstract":"<p><strong>Background: </strong>Despite advancements in targeted therapy and immunotherapy, cutaneous melanoma continues to have a high mortality rate and poor prognosis, with therapies having limited efficacy in advanced melanoma. Therefore, it is crucial to develop novel therapeutics with proven clinical potential. In this study, we evaluated the efficacy of arcyriaflavin A (ArcA), a potent inhibitor of the cyclin D1/CDK4 complex, in suppressing aggressive phenotypes of metastatic melanoma.</p><p><strong>Methods: </strong>The effects of ArcA on viability and cell cycle were evaluated across four melanoma cell lines: WM239A and its metastatic derivatives: 113-6/4L, 131/4-5B1, and 131/4-5B2. Additionally, we performed wound healing and transwell invasion assays, followed by western blot. We further established xenograft mouse models by subcutaneously injecting them with the four melanoma cell lines and measured tumor size and weight biweekly. Immunohistochemistry analysis was performed to compare protein expression.</p><p><strong>Results: </strong>ArcA demonstrated dose-dependent cytotoxicity, selectively targeting melanoma cells without affecting normal cells, and induced G₁ cell cycle arrest. Moreover, ArcA significantly inhibited cell migration and invasion in metastatic melanoma cell lines, accompanied by reduced expression levels of p-GSK-3β (Ser9), MMP-9, and MMP-13, suggesting that its anti-metastatic effects may be partially mediated through GSK-3β, MMP-9, and MMP-13. These findings were further validated using mouse xenograft models; ArcA-treated mice exhibited significantly smaller tumor volumes and lighter tumor weights compared to vehicle-treated mice. Immunohistochemistry further confirmed decreased expression of p-GSK-3β, MMP-9, and MMP-13 in tumor tissues from ArcA-treated mice.</p><p><strong>Conclusions: </strong>Collectively, our findings indicate that ArcA possesses substantial anti-tumor potential, including cytotoxic effects and inhibition of migration and invasion in metastatic melanoma. These results suggest that ArcA could enhance therapeutic efficacy in the treatment of metastatic melanoma.</p>","PeriodicalId":9385,"journal":{"name":"Cancer Cell International","volume":"25 1","pages":"42"},"PeriodicalIF":5.3,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11827473/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143413444","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrative machine learning model of RNA modifications predict prognosis and treatment response in patients with breast cancer.","authors":"Tao Wang, Shu Wang, Zhuolin Li, Jie Xie, Qi Jia, Jing Hou","doi":"10.1186/s12935-025-03651-y","DOIUrl":"10.1186/s12935-025-03651-y","url":null,"abstract":"<p><strong>Background: </strong>Breast cancer, a highly heterogeneous and complex disease, remains the leading cause of cancer-related death among women worldwide. Despite advances in treatment modalities, effective prognostic models and therapeutic strategies are still urgently needed.</p><p><strong>Methods: </strong>We retrospectively analyzed 15 independent breast cancer cohorts to explore the role of RNA modifications in the prognosis of patients with breast cancer. By integrating nine types of RNA modifications, we developed a comprehensive machine learning-based RNA modification signature (CMRS). Furthermore, single-cell RNA sequencing data were analyzed to understand the biological mechanisms underlying CMRS. In addition, immune infiltration levels were evaluated via six different algorithms, and immune checkpoint inhibitor responsiveness was predicted. Moreover, the response of high-CMIS patients to chemotherapy was predicted via multiple datasets. Finally, immunohistochemistry was performed on tissue samples from breast cancer patients to validate protein expression levels.</p><p><strong>Results: </strong>Our analysis revealed five key RNA modification-related genes (ENO1, ARAF, WT1, GADD45A, and BIRC3) associated with breast cancer prognosis. The CMRS model demonstrated high predictive accuracy across multiple cohorts and was significantly correlated with patient survival outcomes. Multiomics analysis revealed that high CMRS was associated with increased tumor mutational burden and distinct mutational signatures, particularly in pathways related to TP53, MYC, and cell proliferation. Single-cell analysis highlighted the involvement of epithelial cells and MYC signaling in high CMRS activity. Cell‒cell communication analysis revealed reduced interaction strength in hig CMRS patients, indicating poor prognosis. Furthermore, low CMRS patients presented increased immune cell infiltration and improved responsiveness to immune checkpoint inhibitors, whereas high CMRS patients were identified as potential candidates for treatment with panobinostat and vincristine.</p><p><strong>Conclusion: </strong>Our study elucidates the significant role of RNA modifications in breast cancer prognosis and treatment. The CMRS model serves as a sensitive biomarker for predicting patient survival and treatment responsiveness, offering a new avenue for personalized therapy in patients with breast cancer.</p>","PeriodicalId":9385,"journal":{"name":"Cancer Cell International","volume":"25 1","pages":"43"},"PeriodicalIF":5.3,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11827143/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143413446","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Rack1 promotes breast cancer stemness properties and tumorigenesis through the E2F1-SOX2 axis.","authors":"Yidi Jia, Luoming Zhang, Wei Zhou, Shuhua Chen, He Zhang, Liming Liu, Hui Guo, Zhiyong Wang, Yanfen Cui, Ruifang Niu, Fei Zhang","doi":"10.1186/s12935-025-03678-1","DOIUrl":"10.1186/s12935-025-03678-1","url":null,"abstract":"<p><strong>Background: </strong>Breast cancer remains the most prevalent malignancy and the leading cause of cancer-related mortality among women worldwide. The primary factors contributing to the deterioration and death of patients with breast cancer are metastasis, recurrence, and drug resistance. These phenomena are closely related to the presence of breast cancer stem cells; however, the exact mechanisms regulating stemness remain to be elucidated. Rack1 (Receptor for Activated C Kinase 1), a well-known versatile scaffold protein, has been implicated in tumorigenesis and progression in numerous cancer types; however, its specific role in breast cancer stemness remains to be elucidated.</p><p><strong>Methods: </strong>Using bioinformatic and immunohistochemical approaches, we validated that the expression level of Rack1 is associated with cancer stemness and affects the prognosis of patients. Through a series of experimental methods including mammosphere formation assay, flow cytometry, qPCR, Western blotting, and CHX assays, we validated at the molecular and cellular levels the mechanism by which Rack1 influences cancer stemness via the E2F1/SOX2 axis. Furthermore, by designing and utilizing lentiviral constructs to establish xenograft tumor models in mice, we further confirmed in vivo the impact of the Rack1/E2F1/SOX2 axis on the tumorigenic capacity of breast cancer cells.</p><p><strong>Results: </strong>Our findings indicate that Rack1 plays a critical role in preserving the stemness characteristics of breast cancer cells. Mechanistically, the observed effects of Rack1 are achieved through the modulation of SOX2 expression, a master transcription factor that regulates cancer cell stemness and maintenance. We further demonstrate that Rack1 increases the stability of the E2F1 protein by inhibiting its ubiquitination and subsequent proteasome-mediated degradation, which in turn transcriptionally upregulates SOX2, thereby maintaining breast cancer cell stemness and tumorigenesis.</p><p><strong>Conclusion: </strong>This study thus unveils a novel mechanism through which Rack1 executes its oncogenic function. This study also demonstrates that targeting the Rack1-E2F-SOX2 axis may be a potential strategy to inhibit breast cancer development and progression.</p>","PeriodicalId":9385,"journal":{"name":"Cancer Cell International","volume":"25 1","pages":"40"},"PeriodicalIF":5.3,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11823217/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143405587","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"miR-485-5p/NQO1 axis drives colorectal cancer progression by regulating apoptosis and aerobic glycolysis.","authors":"Yixuan Wang, Houkun Zhou, Ying Liu, Xingyu Zhao, Shuhao Wang, Zhenhua Lin","doi":"10.1186/s12935-025-03672-7","DOIUrl":"10.1186/s12935-025-03672-7","url":null,"abstract":"<p><strong>Background: </strong>Cancer cells undergo a metabolic shift termed the Warburg effect, transitioning from oxidative phosphorylation to aerobic glycolysis and promoting rapid tumor proliferation. Quinone oxidoreductase (NQO1), a cytosolic flavoprotein, is important for reprogramming cancer cell metabolism. Therefore, NQO1's function in aerobic glycolysis and impact on colorectal cancer (CRC) development and progression was investigated.</p><p><strong>Methods: </strong>The clinical significance of NQO1 was evaluated by analyzing online databases and was substantiated in CRC specimens. NQO1's influence on proliferation, epithelial-mesenchymal transition (EMT), metastasis, apoptosis, and glycolytic pathways in CRC cells was evaluated using in vitro and in vivo experiments. The molecular interactions between NQO1 and microRNA-485-5p (miR-485-5p) were ascertained via quantitative reverse transcription PCR and dual luciferase reporter assays. The molecular mechanisms underlying the miR-485-5p/NQO1 axis and its effects on progression of malignancy and aerobic glycolysis in CRC cell lines were investigated.</p><p><strong>Results: </strong>NQO1 promoted CRC cell proliferation and EMT, augmented their metastatic potential, and suppressed their apoptosis. The NQO1 overexpression-mediated enhancement of glycolytic activity is implicated in the increased proliferation, EMT, and metastatic abilities of, and reduced apoptosis in, CRC cells. Further, miR-485-5p may inhibit the proliferative and invasive traits of CRC cells by directly targeting the 3' untranslated region of NQO1 mRNA.</p><p><strong>Conclusions: </strong>miR-485-5p/NQO1 signaling axis orchestrates aerobic glycolysis, thereby modulating CRC cell proliferation, metastasis, and apoptosis. Our study provides mechanistic perspectives regarding the role of NQO1 in CRC progression.</p>","PeriodicalId":9385,"journal":{"name":"Cancer Cell International","volume":"25 1","pages":"41"},"PeriodicalIF":5.3,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11823044/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143405577","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"PI3Kδ inhibitor linperlisib combined with gemcitabine and oxaliplatin for relapsed or refractory diffuse large B-cell lymphoma: a multicenter, single-arm phase Ib/II trial.","authors":"Peng Sun, Hong Cen, Haiyan Yang, Rui Huang, Zhen Cai, Xuekui Gu, Hanying Bao, Zusheng Xu, Zuhong Xu, Zhi-Ming Li","doi":"10.1186/s12935-025-03669-2","DOIUrl":"10.1186/s12935-025-03669-2","url":null,"abstract":"<p><strong>Background: </strong>This investigation assessed the therapeutic potential of combining linperlisib, a targeted inhibitor of phosphatidylinositol 3-kinase delta (PI3Kδ), with gemcitabine and oxaliplatin (GEMOX) for patients with relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL).</p><p><strong>Methods: </strong>This was a multicenter, phase Ib/II clinical study conducted across six sites in China, enrolling 39 individuals with histologically confirmed R/R DLBCL. The treatment protocol included oral linperlisib alongside GEMOX administered intravenously every three weeks for up to six cycles. The primary efficacy endpoint was the objective response rate (ORR).</p><p><strong>Results: </strong>The ORR observed in the full study population was 53.8% (95% confidence interval [CI]: 37.2-69.9). The median duration of response was 5.7 months (95% CI: 4.3-9.1), and the median progression-free survival was 5.4 months (95% CI: 1.8-6.7). The 1-year OS rate was 65.5% (95% CI: 48.1-78.3). Frequently observed adverse events included decreases in neutrophil counts (74.4%), white blood cell counts (64.1%) and platelet counts (64.1%).</p><p><strong>Conclusions: </strong>This study highlights the potential of linperlisib plus GEMOX as a treatment for R/R DLBCL, demonstrating a tolerable safety profile and encouraging efficacy results.</p><p><strong>Trial registration: </strong>NCT04500561.</p>","PeriodicalId":9385,"journal":{"name":"Cancer Cell International","volume":"25 1","pages":"39"},"PeriodicalIF":5.3,"publicationDate":"2025-02-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11807316/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143373844","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Do wolframin, P-glycoprotein, and GRP78/BiP cooperate to alter the response of L1210 cells to endoplasmic reticulum stress or drug sensitivity?","authors":"Simona Kurekova, Lucia Pavlikova, Mario Seres, Viera Bohacova, Jana Spaldova, Albert Breier, Zdena Sulova","doi":"10.1186/s12935-025-03661-w","DOIUrl":"10.1186/s12935-025-03661-w","url":null,"abstract":"<p><p>In previous research, we revealed that murine leukemia cells L1210 with induced expression of P-glycoprotein (P-gp, a membrane drug transporter, product of the Abcb1 gene) are better able to withstand endoplasmic reticulum (ER) stress (ERS) than their P-gp negative counterparts. This was associated with increased GRP78/BiP expression and modulation of the expression of several other proteins active in the cellular response to ERS (like CHOP, spliced XBP1, 50-kDa ATF6 protein fragment and others) in P-gp positive cells. Wolframin is an ER transmembrane protein, product of the WFS1 gene whose mutations are associated with Wolfram syndrome. However, this protein is frequently overexpressed in cells undergoing ERS and its expression may accompany changes in the above ERS markers. Therefore, our aim in this work was to investigate wolframin expression in P-gp-negative and P-gp-positive murine leukemia L1210 cells in relation to ERS related proteins in normal or ERS condition. We induced ERS in cells either by blocking N-glycosylation in the ER with tunicamycin or by blocking ER Ca²⁺-ATPase activity with thapsigargin, as known ER stressors. The results of this paper demonstrated increased wolframin expression in P-gp positive cells compared to P-gp negative cells. Immunoprecipitation experiments revealed the formation of complexes between wolframin and ERS related proteins (PERK, ATF6 and GRP78/BiP), the amount of which varied depending on the presence of the above ER stressors.</p>","PeriodicalId":9385,"journal":{"name":"Cancer Cell International","volume":"25 1","pages":"35"},"PeriodicalIF":5.3,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11806844/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143370471","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Characterization of G2/M checkpoint classifier for personalized treatment in uterine corpus endometrial carcinoma.","authors":"Yiming Liu, Yusi Wang, Shu Tan, Xiaochen Shi, Jinglin Wen, Dejia Chen, Yue Zhao, Wenjing Pan, Zhaoyang Jia, Chunru Lu, Ge Lou","doi":"10.1186/s12935-025-03667-4","DOIUrl":"10.1186/s12935-025-03667-4","url":null,"abstract":"<p><strong>Background: </strong>Uterine Corpus Endometrial Carcinoma (UCEC) is a highly heterogeneous tumor, and limitations in current diagnostic methods, along with treatment resistance in some patients, pose significant challenges for managing UCEC. The excessive activation of G2/M checkpoint genes is a crucial factor affecting malignancy prognosis and promoting treatment resistance.</p><p><strong>Methods: </strong>Gene expression profiles and clinical feature data mainly came from the TCGA-UCEC cohort. Unsupervised clustering was performed to construct G2/M checkpoint (G2MC) subtypes. The differences in biological and clinical features of different subtypes were compared through survival analysis, clinical characteristics, immune infiltration, tumor mutation burden, and drug sensitivity analysis. Ultimately, an artificial neural network (ANN) and machine learning were employed to develop the G2MC subtypes classifier.</p><p><strong>Results: </strong>We constructed a classifier based on the overall activity of the G2/M checkpoint signaling pathway to identify patients with different risks and treatment responses, and attempted to explore potential therapeutic targets. The results showed that two G2MC subtypes have completely different G2/M checkpoint-related gene expression profiles. Compared with the subtype C2, the subtype C1 exhibited higher G2MC scores and was associated with faster disease progression, higher clinical staging, poorer pathological types, and lower therapy responsiveness of cisplatin, radiotherapy and immunotherapy. Experiments targeting the feature gene KIF23 revealed its crucial role in reducing HEC-1A sensitivity to cisplatin and radiotherapy.</p><p><strong>Conclusion: </strong>In summary, our study developed a classifier for identifying G2MC subtypes, and this finding holds promise for advancing precision treatment strategies for UCEC.</p>","PeriodicalId":9385,"journal":{"name":"Cancer Cell International","volume":"25 1","pages":"34"},"PeriodicalIF":5.3,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11806828/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143370466","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comprehensive analysis of α2,3-sialyltransferases as prognostic biomarkers and immunotherapy targets in kidney renal clear cell carcinoma.","authors":"Yuli Jian, Kangkang Yang, Jinjing Li, Ling Tang, Guang Zeng, Xiaoxin Sun, Xiao Yu, Abdullah Al-Danakh, Qiwei Chen, Deyong Yang, Shujing Wang","doi":"10.1186/s12935-025-03640-1","DOIUrl":"10.1186/s12935-025-03640-1","url":null,"abstract":"<p><p>Kidney renal clear cell carcinoma (KIRC), a therapy-resistant aggressive kidney cancer, exhibits resistance to immune checkpoint inhibitors. Altered sialylation is involved in tumor development, affecting immune microenvironment dynamics. In the study, through systematic bioinformatics analysis and experimental verification, we demonstrated that ST3Gal5 expression was elevated in tumor tissues of KIRC patients, correlating with poor prognosis, and ST3Gal1 was downregulated and associated with a better prognosis. Immunohistochemistry analysis confirmed the expression patterns of ST3Gal1 and ST3Gal5 in 30 KIRC patients. Furthermore, KIRC patients were stratified into two clusters based on ST3Gal1 and ST3Gal5 levels using consensus clustering to investigate their roles in KIRC tumorigenesis, immune characteristics and treatment sensitivity. KIRC patients in Cluster 2, characterized by increased ST3Gal5 and downregulated ST3Gal1 expression, exhibited increased expression of immune checkpoints, immune cell infiltration, immune escape scores, and worse prognosis. Knockdown of ST3Gal5 in KIRC cell lines (786-O and 769-P) resulted in reduced tumor proliferation, migration, and invasion in vivo and in vitro. Together, the dysregulation of sialyltransferases (ST3Gal1 and ST3Gal5) in KIRC influences tumorigenesis and immune responses. These findings underscore the potential of ST3Gal1 and ST3Gal5 as prognostic factors and immunotherapy targets for KIRC.</p>","PeriodicalId":9385,"journal":{"name":"Cancer Cell International","volume":"25 1","pages":"36"},"PeriodicalIF":5.3,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11806589/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143370468","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}