Yunfei Zhang, Jing Wu, Abudusalamu Tuersunmaimaiti, Gang Yao, Xiapukaiti Fulati, Yilizhati Azhati, Alimujiang Mamuti, Tao Li, Tuerhongjiang Tuxun
{"title":"A prognostic nomogram to predict clinical outcomes of patients with primary malignant and benign retroperitoneal tumors.","authors":"Yunfei Zhang, Jing Wu, Abudusalamu Tuersunmaimaiti, Gang Yao, Xiapukaiti Fulati, Yilizhati Azhati, Alimujiang Mamuti, Tao Li, Tuerhongjiang Tuxun","doi":"10.1007/s12672-025-03730-6","DOIUrl":"10.1007/s12672-025-03730-6","url":null,"abstract":"<p><strong>Background: </strong>Primary retroperitoneal tumor (PRT) is a relatively rare tumor with diverse histological and molecular types. We aim to develop and validate a concise prognostic nomogram for patients with benign and malignant PRT.</p><p><strong>Methods: </strong>The clinical data of 206 PRT patients who underwent surgical management in authors' institution during January 2016 and December 2021 were analyzed. Logistic regression was used to select independent risk variables of binary outcome, while COX regression was performed for time-to-event. A predictive nomogram was developed based on multivariate analyses.</p><p><strong>Results: </strong>Of the reported 206 PRTs, 113 patients were benign (54.85%) and 93 (45.15%) were malignant. Radical resection, extended radical resection and cytoreductive resection were performed in 141, 50 and 15 patients, respectively. The comprehensive complication index (CCI) was higher than 26.2% in 14 cases. Postoperative recurrence was experienced in 20 (9.7%) cases during the median 49 months. Nomogram was developed to predict severe complication and parameters included time of surgery, loss of blood and type of surgery with a moderate prediction capability [Area under curve (AUC) = 0.64)] after interval validation. While model for postoperative recurrence prediction includes parameters as chemotherapy, metastasis, combined resection and time of surgery with acceptable performance (AUC = 0.913). Overall survival is related to tumor size, metastasis and pathology as risk factors and the prediction capability was good (AUC = 0.800).</p><p><strong>Conclusion: </strong>The proposed nomogram showed favorable predictive accuracy for prognosis in patients with PRTs. This has the potential to contribute to clinical decision-making.</p>","PeriodicalId":11148,"journal":{"name":"Discover. Oncology","volume":"16 1","pages":"1892"},"PeriodicalIF":2.9,"publicationDate":"2025-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12528585/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145291575","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Identification of an E2Fs-based gene signature for predicting prognosis and therapeutic response in colorectal cancer.","authors":"Feifan Zhang, Zhiwei Sun, Zhenyu Zhang, Kexin Jiang, Bowen Wei, Xiaoqi Yu, Yunfei Zuo, Shuangyi Ren","doi":"10.1007/s12672-025-02615-y","DOIUrl":"10.1007/s12672-025-02615-y","url":null,"abstract":"<p><p>E2F family genes are common transcription factors, abnormal in several malignant tumors. However, their complex involvement in colorectal cancer, particularly in prognosis, immune infiltration, and mutational landscape, remains unclear. We conducted a study using gene expression data from the TCGA and GEO datasets to examine the abnormal expression of E2Fs in colorectal cancer. And we performed consensus clustering and differential gene expression analyses to identify E2Fs-related genes. Then, we used Lasso regression and multivariate Cox regression to create a prognostic risk model for colorectal cancer. We analyzed the differences between the E2Fs-based gene risk and various clinical characteristics, gene mutations, immune cell infiltration, immunotherapy responses, and drug sensitivity using clinicopathological data, single-cell RNA sequences, multiple immune algorithms. Finally, we have developed a prognostic risk model that includes FMO5, NDUFA11, LIPG, FIGNL1, MOGAT2, and GZMB. We observed significant differences in clinical characteristics, immune cell infiltration, gene mutation landscapes, immunotherapy responses, and drug sensitivity between the high-risk and low-risk groups. The novel E2Fs-based gene risk model shows significant potential for contributing to the evaluation of prognosis and predicting immunotherapeutic outcomes for colorectal cancer patients.</p>","PeriodicalId":11148,"journal":{"name":"Discover. Oncology","volume":"16 1","pages":"1893"},"PeriodicalIF":2.9,"publicationDate":"2025-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12528531/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145291583","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Xiao-Li Wu, Di Hu, Guo-Fa Xu, Mei-Yu Zhou, Bin Li, Xiao-Qiao Hu, Gen-Dou Zhou, Ya Fu, Rui Huang, Shou-Yan Xiang, Miao-Miao Tao, Hong-Bo Ma
{"title":"Neutrophil extracellular traps (NETs)-score: a novel prognostic marker for colorectal cancer patients.","authors":"Xiao-Li Wu, Di Hu, Guo-Fa Xu, Mei-Yu Zhou, Bin Li, Xiao-Qiao Hu, Gen-Dou Zhou, Ya Fu, Rui Huang, Shou-Yan Xiang, Miao-Miao Tao, Hong-Bo Ma","doi":"10.1007/s12672-025-03708-4","DOIUrl":"10.1007/s12672-025-03708-4","url":null,"abstract":"<p><strong>Background: </strong>Colorectal cancer (CRC) ranks as the third most prevalent cancer globally, displaying significant tendencies towards recurrence and metastasis. Advanced CRC typically necessitates systemic treatments such as chemotherapy, targeted therapy, and immunotherapy, yet the development of primary and acquired drug resistance remains a significant challenge. Neutrophil extracellular traps (NETs) represent a complex network structure comprising DNA, histones, and antimicrobial peptides generated by activated neutrophils, which have been implicated in promoting cancer progression. However, the precise mechanisms underlying the interaction between NETs-related gene signatures and cancer cells remain poorly understood.</p><p><strong>Methods: </strong>The gene expression profile of TCGA-CRC was obtained from the Xena database. Using the expression levels of 69 initial NETs biomarkers, a LASSO Cox regression model was used to develop a 10-gene NETs score. This score was then comprehensively analyzed, focusing on various aspects such as the tumor microenvironment (TME), drug resistance, tumor mutations, and immunotherapy response.</p><p><strong>Results: </strong>A prognostic model for NETs was developed using multivariate Cox regression and LASSO regression analysis. A customized nomogram was developed to improve the forecast precision of the NETs-score. The NETs-score is involved in the TME and clinicopathological characteristics, where a lower score is associated with a more favorable prognosis. Further examination indicated that the NETs-score can predict how well a patient will respond to chemotherapy and identify those who could potentially gain advantages from anti-CTLA4 and PD-L1 treatments.</p><p><strong>Conclusion: </strong>The NETs-score introduces a new, effective, and precise prognostic model for CRC, enhancing the prediction of responses to chemotherapy and immunotherapy. This advancement also propels personalized cancer treatment strategies in the realms of chemotherapy and immunotherapy.</p>","PeriodicalId":11148,"journal":{"name":"Discover. Oncology","volume":"16 1","pages":"1896"},"PeriodicalIF":2.9,"publicationDate":"2025-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12528602/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145291686","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Liyuan Fan, Liang Shi, Zhongchao Wang, Jinghan Wang, Yandong Mu
{"title":"Ferroptosis and radiotherapy-related genes in head and neck squamous cell carcinoma: diagnostic and prognostic significance.","authors":"Liyuan Fan, Liang Shi, Zhongchao Wang, Jinghan Wang, Yandong Mu","doi":"10.1007/s12672-025-03713-7","DOIUrl":"10.1007/s12672-025-03713-7","url":null,"abstract":"<p><strong>Background: </strong>Head and Neck Squamous Cell Carcinoma (HNSCC) is an aggressive malignancy with poor prognosis and low five-year survival rates. Ferroptosis, an iron-dependent form of cell death, has emerged as a potential factor in cancer therapy. This study aimed to identify differentially expressed genes (DEGs) associated with HNSCC, ferroptosis, and radiotherapy, and to develop a diagnostic model to establish novel biomarkers, early diagnosis and individualized therapy.</p><p><strong>Methods: </strong>We analyzed TCGA-HNSCC, GSE6631, and GSE107591 datasets to identify Ferroptosis- and Radiotherapy-Related Differentially Expressed Genes (F&RRDEGs).Ferroptosis & radiotherapy scores were calculated, followed by immune infiltration and immunotherapy analyses. A Cox prognostic model was evaluated using nomograms, calibration curves, and decision curve analysis. Real-time quantitative PCR (RT-qPCR) and Western blotting (WB) were used for experimental validation.</p><p><strong>Results: </strong>11 F&RRDEGs were identified classifying two subtypes related to HNSCC.Significant differences were found in immune cell infiltration and immunophenoscore in CTLA4 and PD1/PD-L1/PD-L2 + CTLA4 between high and low ferroptosis & radiotherapy scores(F&Rs) groups. The 1-year calibration curve of the prognostic risk model showed better and more accurate performance and performance for the five-year prediction. RT-qPCR identified significant differences in the genes ALOX12, EMP1, PIM1, and CA9 between the control and HNSCC groups, with WB confirming radiotherapy-induced upregulation of VDAC1/TFRC (pro-ferroptosis) and downregulation of GPX4/SLC7A11/FTH1 (anti-ferroptosis) in irradiated HNSCC cells.</p><p><strong>Conclusion: </strong>ALOX12, EMP1, PIM1, and CA9 exhibited promising potential as diagnostic biomarkers. This study applies immune infiltration analysis to HNSCC research, offering fresh perspectives on patient-specific treatment plans, and accelerating the creation of focused therapies.</p>","PeriodicalId":11148,"journal":{"name":"Discover. Oncology","volume":"16 1","pages":"1895"},"PeriodicalIF":2.9,"publicationDate":"2025-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12528569/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145291572","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Shumin Li, Beibei Xu, Guanghui Wang, Luan Xu, Liya Ding, Xiaopei Wu, Baoying Zheng, Yuefeng Han
{"title":"Pan-cancer analysis of INHBA indicates its potential prognostic value and correlation with HNSC and LIHC.","authors":"Shumin Li, Beibei Xu, Guanghui Wang, Luan Xu, Liya Ding, Xiaopei Wu, Baoying Zheng, Yuefeng Han","doi":"10.1007/s12672-025-03505-z","DOIUrl":"10.1007/s12672-025-03505-z","url":null,"abstract":"<p><strong>Background: </strong>INHBA is a member of the TGF-β superfamily and is overexpressed in a variety of cancers and affects prognosis.However, its pan-cancer expression profile and specific roles in HNSC and LIHC remain poorly understood.</p><p><strong>Methods: </strong>We used several databases such as TCGA to study the pan-cancer effects of INHBA, including the expression of INHBA and its correlation with clinical survival, immune checkpoints, tumor stemness scores, prognostic value, immunomodulators, genomic profiles, immune profiling, immunotherapy and functional enrichment; and further analyzed its relationship with HNSC and LIHC.</p><p><strong>Results: </strong>First, we observed that the expression level of INHBA was elevated in most tumor tissues compared to non-tumor tissues, and that high expression of INHBA may have a higher prognostic value in some cancers. In addition, INHBA was significantly associated with immune checkpoints, immunomodulators, prognosis, immunomodulatory genes, tumor stemness score, cellular functional status, and immune infiltration in most tumors. Finally, further analysis of INHBA-associated gene enrichment, mutation sites and types, RNA modifications, and genomic heterogeneity showed that the main mutation types of INHBA were missense mutations and that INHBA played a very important role in HNSC and LIHC; and immunotherapy analysis also suggested that low expression of INHBA might result in better specific immunotherapy response.</p><p><strong>Conclusion: </strong>This study comprehensively reveals the important functions of INHBA in different types of cancer. It also has the potential to identify INHBA as a potential biomarker for predicting treatment response. This may help us better understand how INHBA works in cancer and provide valuable insights for developing personalized treatments.</p>","PeriodicalId":11148,"journal":{"name":"Discover. Oncology","volume":"16 1","pages":"1890"},"PeriodicalIF":2.9,"publicationDate":"2025-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12528627/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145291614","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Strategies to reduce intestinal toxicity in neoadjuvant management of locally advanced rectal cancer.","authors":"Hoda Mahdavi, Sahar Dashti, Shima Jafari","doi":"10.1007/s12672-025-03526-8","DOIUrl":"10.1007/s12672-025-03526-8","url":null,"abstract":"<p><p>The management of locally advanced rectal cancer has progressively evolved to improve both survival outcomes and quality of life. Intestinal toxicity is a prevalent side-effect of pelvic radiotherapy affecting most patients. The pursuit of neoadjuvant intensified treatment strategies to enhance response rates or facilitate organ preservation may lead to an increased likelihood of late toxicity, depending on radiation technique and chemotherapy intensity. This narrative review synthesizes current knowledge on radiation-induced intestinal toxicity, refines effective strategies, with an emphasis on studies evaluating techniques to reduce both unintended and intended radiation exposure to the small intestine in locally advanced rectal cancer patients, and highlights their clinical significance.</p>","PeriodicalId":11148,"journal":{"name":"Discover. Oncology","volume":"16 1","pages":"1886"},"PeriodicalIF":2.9,"publicationDate":"2025-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12528533/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145291683","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Zahra Farjami, Zahra Mohammadzadeh, Bita Saifi, Mahasti Tavakoli Nezhad, Mohammad Mehdi Akbarin
{"title":"The molecular aspects in prostatic cancer, unraveling the role of CDKs in prostate cancer progression.","authors":"Zahra Farjami, Zahra Mohammadzadeh, Bita Saifi, Mahasti Tavakoli Nezhad, Mohammad Mehdi Akbarin","doi":"10.1007/s12672-025-03605-w","DOIUrl":"10.1007/s12672-025-03605-w","url":null,"abstract":"<p><strong>Background: </strong>Prostate cancer (PCa) is one of the leading causes of morbidity and mortality in the world, it becomes imperative to investigate the molecular mechanisms underlying practical therapeutic approaches. Cyclin-dependent kinases (CDKs) are critical regulators of cell cycle progression, and their dysregulation has been implicated in PCa.</p><p><strong>Methods: </strong>This review synthesizes recent findings on CDK-mediated signaling pathways and their role in PCa progression. The overall goal of this review article is to elucidate the molecular mechanisms by which CDK molecules contribute to the development, progression, and metastasis of PCa.</p><p><strong>Results: </strong>Elevated expression of CDK1, CDK3, CDK5, and CDK16 is associated with poorer outcomes, and specifically, high CDK3 expression correlates with shorter progression-free survival.</p><p><strong>Conclusions: </strong>Targeting CDKs, particularly CDK3 and CDK4/6, may represent a promising therapeutic strategy for PCa.</p>","PeriodicalId":11148,"journal":{"name":"Discover. Oncology","volume":"16 1","pages":"1900"},"PeriodicalIF":2.9,"publicationDate":"2025-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12528570/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145291642","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Clinicopathological characteristics and molecular genetic analysis of inflammatory and nested testicular sex cord tumor: a case report and literature review.","authors":"Yan Wang, Yun Xi, Meijuan Wu","doi":"10.1007/s12672-025-03704-8","DOIUrl":"10.1007/s12672-025-03704-8","url":null,"abstract":"<p><strong>Background: </strong>Inflammatory and nested testicular sex cord tumor (IN-SCT) is a newly defined and rare variant of sex cord-stromal tumors, characterized by EWSR1::ATF1 gene fusion, prominent inflammatory infiltration, and aggressive behavior, often leading to misdiagnosis as lymphoma or seminoma. This study aims to systematically analyze the clinicopathological and molecular features of IN-SCT through a case report and comprehensive literature review, exploring its diagnostic pitfalls and therapeutic strategies.</p><p><strong>Case presentation: </strong>A 36-year-old male presented with painless left testicular enlargement. Ultrasound revealed a 6.0 × 5.0 × 3.3 cm heterogeneous mass with irregular vascularity. Initial pathological evaluation after radical orchiectomy at an outside hospital favored a diagnosis of seminoma. However, external consultation raised suspicion of ALK-negative anaplastic large cell lymphoma (ALCL) based on CD30 immunoreactivity. Further histopathological examination at our institution revealed tumor cells arranged in nests and solid patterns, with extensive inflammatory infiltration. Immunohistochemistry (IHC) demonstrated weak positivity for inhibin-α and diffuse positivity for CD30. Fluorescence in situ hybridization (FISH) confirmed EWSR1 gene rearrangement, leading to a final diagnosis of IN-SCT.</p><p><strong>Treatment and outcome: </strong>The patient underwent six cycles of platinum-based chemotherapy following orchiectomy. No evidence of recurrence was observed at the 10-month follow-up.</p><p><strong>Conclusion: </strong>IN-SCT is a diagnostically challenging tumor characterized by the triad of inflammatory stroma, EWSR1::ATF1 fusion, and aggressive clinical behavior. Accurate recognition of its unique features supports its classification as a distinct entity. Surgical excision followed by adjuvant chemotherapy may benefit patients with advanced disease. The distinct molecular profile of IN-SCT may provide future directions for targeted therapy and diagnostic refinement.</p>","PeriodicalId":11148,"journal":{"name":"Discover. Oncology","volume":"16 1","pages":"1902"},"PeriodicalIF":2.9,"publicationDate":"2025-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12528643/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145291543","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Suppressing CDCA8/CDK1 improves oral squamous cell carcinoma by modulating proliferation, apoptosis, cell cycle and migration.","authors":"Jiang Zhu, Chen Chu, Yu Xue, Wei Guan, Jianping Qiu, Aijun Guo, Weiming Chu","doi":"10.1007/s12672-025-03648-z","DOIUrl":"10.1007/s12672-025-03648-z","url":null,"abstract":"<p><p>We aimed to clarify the role of CDCA8/CDK1 in the progression of oral squamous cell carcinoma (OSCC) and the potential mechanisms. To explore the CDCA8 expression in OSCC, clinical samples were collected. In vitro, CAL-27 cells were transfected with short hairpin RNA (shRNA) to silence CDCA8, and then proliferation, apoptosis, cell cycle and migration were evaluated. KEGG analysis was used to explore the causal association of CDCA8 and CDK1 during the development of OSCC. CDK1 inhibitor RO3306 and overexpression of CDK1 were used to clarify the regulatory role of CDK1 in OSCC. In vivo, mice were injected with shCDCA8 to deplete CDCA8 based on establishing a model of OSCC. We found that CDCA8 was highly expressed in OSCC tissues and cell lines. In vitro experiments, suppressing CDCA8 in CAL-27 cells improved OSCC, characterized by increased apoptosis and decreased proliferation and migration. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis revealed that cell cycle formed a direct interaction with CDCA8 and inhibition of CDCA8 efficiently reduced levels of CDK1 and CDK2. Additional experiments showed that CDCA8-activated CDK1 was the key regulator of OSCC. In vivo, we verified that depletion of CDCA8 inhibited proliferation and metastasis of OSCC. CDCA8-activated CDK1 acts a crucial role in the development of OSCC by modulating cell growth, migration, and metastasis.</p>","PeriodicalId":11148,"journal":{"name":"Discover. Oncology","volume":"16 1","pages":"1898"},"PeriodicalIF":2.9,"publicationDate":"2025-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12528644/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145291698","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Dandan Wang, Xuejian Wang, Lin Chen, Huiying Wang, Xiangfei Meng, Zhenwei Miao, Yang Zhao
{"title":"Development of an ADME gene signature for prognostic and therapeutic stratification in gastric cancer.","authors":"Dandan Wang, Xuejian Wang, Lin Chen, Huiying Wang, Xiangfei Meng, Zhenwei Miao, Yang Zhao","doi":"10.1007/s12672-025-03729-z","DOIUrl":"10.1007/s12672-025-03729-z","url":null,"abstract":"<p><p>A pivotal determinant of tumor therapy efficacy lies in the absorption, distribution, metabolism, and excretion (ADME) processes that govern drug disposition within the body. We intended to establish a prognostic model incorporating ADME-related genes to forecast the survival rate and therapeutic response in gastric cancer (GC) patients. By integrating Cox regression and LASSO analysis for dimensionality reduction and feature selection, we identified a stable five-gene signature with significant prognostic value. Subsequently, the stability of the model was verified. A nomogram incorporating these genes was constructed and integrated with a clinicopathological feature prediction system to improve its clinical applicability. The results revealed a robust correlation between ADME-related genes and the survival outcomes of GC patients. The ADME-based gene signature serves as a robust prognostic biomarker for evaluating the survival outcomes. Furthermore, immune cell infiltration and functional analyses demonstrated distinct patterns between the two strata, with the high-risk stratum exhibiting superior drug sensitivity. Finally, in vitro validation experiments using AGS and HGC-27 cell lines confirmed that elevated CYP2A6 expression promotes the progression of GC. This finding indicates that CYP2A6 may be a new biomarker in the therapeutic management of the disease.</p>","PeriodicalId":11148,"journal":{"name":"Discover. Oncology","volume":"16 1","pages":"1888"},"PeriodicalIF":2.9,"publicationDate":"2025-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12528583/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145291541","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}