Discover. Oncology最新文献

{"title":"Cross-tissue transcriptome-wide analysis reveals novel insights into thyroid cancer etiology.","authors":"Yue Zhu, Yu Luo, Yuye Zhang, Yixuan Wang, Zhangqi Gu, Jinyan Liu, Ancheng Qin, Weifeng Qian","doi":"10.1007/s12672-025-03194-8","DOIUrl":"10.1007/s12672-025-03194-8","url":null,"abstract":"<p><strong>Background: </strong>Despite significant advances made by genome-wide association studies (GWAS) in the genetic exploration of tumors such as thyroid cancer (TC), the precise pathogenic genes and underlying biological mechanisms of TC remain unclear.</p><p><strong>Methods: </strong>We performed a transcriptome-wide association study (TWAS) to identify the susceptibility genes for TC. Three complementary methods: FUSION (Functional Summary-based Imputation), FOCUS (Fine-mapping Of CaUsal gene Sets), and Multi-marker Analysis of GenoMic Annotation (MAGMA) were used to validate key gene discoveries. Additionally, MAGMA was used to examine the functional enrichment of single nucleotide polymorphisms (SNPs) associated with TC. Conditional and joint analysis, as well as fine mapping techniques, were employed to deepen our understanding of TC's genetic architecture. To explore causal relationships, we conducted Mendelian randomization analysis, while colocalization analysis was used to provide potential shared SNPs between key genes and TC risk.</p><p><strong>Results: </strong>Through the comprehensive application of three TWAS methods, we identified three potential susceptibility genes closely associated with TC risk. Mendelian randomization analysis provided causal links between the TGFB2, SMAD3 and SDCCAG8 genes and TC. Colocalization analysis further revealed that TGFB2 (rs1764705), SMAD3 (rs17293632), and SDCCAG8 (rs2490395) may share genetic signals between GWAS and expression quantitative trait loci (eQTL), indicating common pathways in TC pathogenesis. The study highlighted differences in the expression of significant genes in normal and thyroid cancer tissues at the transcriptome level and investigated their relationship with the tumor microenvironment.</p><p><strong>Conclusion: </strong>This investigation uncovered three new genes associated with increased TC risk, shedding light on the genetic underpinnings of TC and aiding in a deeper comprehension of its complex genetic architecture.</p>","PeriodicalId":11148,"journal":{"name":"Discover. Oncology","volume":"16 1","pages":"1359"},"PeriodicalIF":2.8,"publicationDate":"2025-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12270988/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144658615","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":"miRNA regulation of the Akt/mTOR pathway in oral squamous cell carcinoma: a focused review.","authors":"Shazia Fathima Jaffer Hussain, Mohammad Fareed, Mohmed Isaqali Karobari","doi":"10.1007/s12672-025-03073-2","DOIUrl":"10.1007/s12672-025-03073-2","url":null,"abstract":"<p><p>Oral squamous cell carcinoma (OSCC) contributes significantly to global cancer mortality, characterized by a progression from hyperplasia to invasive cancer through a series of genetic and epigenetic alterations. Central to this progression is the Akt/mTOR signaling pathway, which regulates cell proliferation and survival. This review examines the role of microRNAs (miRNAs) in modulating the Akt/mTOR pathway and their implications for OSCC. The Akt/mTOR pathway, activated by receptor tyrosine kinases and involving the PI3K/AKT/mTOR complexes, is crucial for tumor cell growth and metabolism. Dysregulation of this pathway is frequently observed in OSCC, leading to increased proliferation, survival, and metastasis. miRNAs, such as miR-21, miR-99, and miR-145, play significant roles in regulating this pathway by influencing key components like Akt and mTOR. These miRNAs can act as oncogenes or tumor suppressors, affecting cancer progression and response to therapy. The review highlights the potential of targeting miRNAs for OSCC treatment, including strategies to restore normal miRNA levels or inhibit aberrant miRNAs. Such targeted therapies offer promise for improving treatment outcomes and overcoming drug resistance in OSCC.</p>","PeriodicalId":11148,"journal":{"name":"Discover. Oncology","volume":"16 1","pages":"1355"},"PeriodicalIF":2.8,"publicationDate":"2025-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12271007/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144658679","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":"Expression and prognostic value of SEC13 across multiple tumour types and its association with the regulation by Pulsatilla chinensis: a multi-omics and Mendelian Randomization Study.","authors":"Huaqing Leng, Xin Luan, Ming Li","doi":"10.1007/s12672-025-03148-0","DOIUrl":"10.1007/s12672-025-03148-0","url":null,"abstract":"<p><strong>Background: </strong>Cancer remains one of the leading causes of death worldwide. The lack of effective early diagnostic markers and comprehensive treatment strategies continues to limit progress in clinical outcomes. Although targeted therapies have brought some improvement, the need for more reliable and efficient treatment options persists. SEC13, a protein involved in cellular energy metabolism and nucleocytoplasmic transport, has been suggested to play a role in tumour progression. This study aims to explore the potential role of SEC13 across various types of cancer, with a particular focus on its value as a diagnostic and prognostic marker, using Mendelian randomization analysis.</p><p><strong>Methods: </strong>In this study, we conducted a comprehensive analysis of SEC13 expression using data from TCGA and GTEx, and explored associated pathways through gene set enrichment analysis. Single-cell transcriptomic data were integrated to investigate the cell-type-specific expression of SEC13 within the tumour microenvironment. In parallel, we examined the regulatory potential of the traditional Chinese compound PC using publicly available gene expression profiles. Causal inference between SEC13 and cancer susceptibility was assessed through Mendelian randomization and data from the BEST database.</p><p><strong>Results: </strong>SEC13 was found to be significantly upregulated in several cancer types. Higher expression levels appeared to be associated with more advanced tumour stages and poorer survival outcomes. However, Mendelian randomization did not provide clear evidence for a direct causal link between SEC13 and any of the six cancers studied (P-IVW > 0.05). Interestingly, a negative association was observed between SEC13 expression and chemotherapy sensitivity, which may point to a possible role in drug resistance. Additionally, single-cell analysis revealed marked expression of SEC13 in fibroblasts, tumour-associated macrophages, and endothelial cells, suggesting a possible role in immune modulation and microenvironmental remodelling.</p><p><strong>Conclusions: </strong>These findings highlight the prognostic relevance of SEC13 across multiple cancers and suggest that it may be regulated by PC, potentially contributing to anti-tumour activity. While Mendelian randomization did not reveal a definitive causal link, the collective evidence warrants further investigation and external validation, particularly regarding SEC13 as a therapeutic target and its possible pharmacological modulation.</p>","PeriodicalId":11148,"journal":{"name":"Discover. Oncology","volume":"16 1","pages":"1353"},"PeriodicalIF":2.8,"publicationDate":"2025-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12271015/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144658616","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":"Global trends in sarcopenia and cancer over the past 10 years: a bibliometric analysis.","authors":"Ruoshuang Liu, Menghuan Wu, Xia Cheng, Chundi Zhou, Caiqin Cheng, Lijun Feng, Yirong Shen","doi":"10.1007/s12672-025-03185-9","DOIUrl":"10.1007/s12672-025-03185-9","url":null,"abstract":"<p><strong>Background: </strong>Sarcopenia is common among patients with cancer. The alterations in the internal milieu of cancer patients, coupled with the adverse effects of antineoplastic therapies, markedly augment the susceptibility to sarcopenia. We aimed to clarify the current research status and investigate future trends in sarcopenia and cancer research.</p><p><strong>Methods: </strong>Publications on sarcopenia and cancer from the past decade were retrieved from the Web of Science database. VOSviewer, CiteSpace, and Bibliometrix R package were used for visualization analysis.</p><p><strong>Results: </strong>A total of 3749 publications were retrieved between 2014 and 2023. These publications were written by 21,507 authors affiliated with 4068 organizations in 76 countries/regions. Japan, the United States, and China constituted the primary contributors to the majority of the publications. The top three research institutions with the highest outputs in this field were the University of Alberta, Wenzhou Medical University, and Maastricht University. The Journal of Cachexia Sarcopenia and Muscle served as the pivotal and most cited journal in this field. Baracos VE from the University of Alberta was the author with the most publications. \"Sarcopenic obesity\", \"Radiomics\", and \"Neutrophil/lymphocyte ratio\" were highly focused topics in current research.</p><p><strong>Conclusion: </strong>This study conducted the first bibliometric analysis of literature on sarcopenia and cancer. A systematic analysis of the present research status and emerging trends in this field provides important references for future research.</p>","PeriodicalId":11148,"journal":{"name":"Discover. Oncology","volume":"16 1","pages":"1358"},"PeriodicalIF":2.8,"publicationDate":"2025-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12271044/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144658675","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":"Risk factors and prognostic analysis of endometrial cancer with para-aortic lymph node metastasis.","authors":"Feng Cheng, Li Yang, Qiang Wen, Jianying Xu, Feng Shao","doi":"10.1007/s12672-025-03191-x","DOIUrl":"10.1007/s12672-025-03191-x","url":null,"abstract":"<p><strong>Background: </strong>Assessment of lymph node involvement plays a pivotal role in the surgical staging of endometrial cancer (EC), offering essential prognostic information. In this study, we aimed to identify predictors of para-aortic lymph node metastasis, assess survival outcomes, and refine surgical strategies for lymphadenectomy in patients with EC.</p><p><strong>Methods: </strong>A retrospective analysis was performed on 713 patients with endometrial cancer who underwent comprehensive staging surgery between July 2016 and July 2019. Clinical, pathological, and follow-up data were systematically collected. Univariate and multivariate logistic regression analyses were conducted to identify risk factors, and survival outcomes were evaluated using Kaplan-Meier analysis.</p><p><strong>Results: </strong>Among 713 patients with endometrial cancer, lymph node metastasis was observed in 70 cases (9.8%), including 43 (6.0%) with para-aortic lymph node (PAN) involvement. Multivariate analysis identified LVSI, pelvic lymph node (PLN) metastasis, and elevated CA125 as independent predictors of PAN metastasis. Non-endometrioid histologies, particularly serous carcinoma, were associated with significantly higher PAN involvement. The 5-year survival rate for patients with PAN metastasis was 62.8%. Patients with isolated PAN metastasis (PLN - PAN+) had better 5-year OS (78.6%) than those with both PLN and PAN involvement (55.2%), though not statistically significant (log-rank P = 0.173).</p><p><strong>Conclusions: </strong>Para-aortic lymph node (PAN) metastasis is rare in early-stage, low-risk endometrial cancer, and routine dissection may be safely omitted. However, para-aortic lymphadenectomy remains essential for patients with high-risk features, such as non-endometrioid histology, lymphovascular space invasion (LVSI), pelvic node metastasis, and elevated CA125 levels. Notably, uterine serous carcinoma is associated with frequent nodal spread and poor five-year survival.</p>","PeriodicalId":11148,"journal":{"name":"Discover. Oncology","volume":"16 1","pages":"1344"},"PeriodicalIF":2.8,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12267712/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144641977","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":"Correlation between CTMP expression levels and resistance to trastuzumab in HER2 + metastatic breast cancer.","authors":"Mania Makhoul, Maher Saifo, Fariz Ahmad, Jumana Saleh","doi":"10.1007/s12672-025-03210-x","DOIUrl":"10.1007/s12672-025-03210-x","url":null,"abstract":"<p><strong>Background: </strong>The combination of trastuzumab and chemotherapeutic drugs improves the prognosis of patients with metastatic disease and reduces the mortality. However, trastuzumab resistance has limited the remarkable improvement of this drug. The carboxyl-terminal modulator protein (CTMP) is involved in the regulation of various cancers through positive or negative regulation of Akt. In the HER2-positive SkBR3 breast cancer cell line, CTMP overexpression increases Akt phosphorylation at Thr308 and Ser473. Therefore, CTMP might mediate trastuzumab resistance. The main objective of the paper is to explore the role of CTMP in trastuzumab efficacy in HER2 + metastatic breast cancer (MBC) patients.</p><p><strong>Patients & methods: </strong>Ninety-six patients received trastuzumab in combination with chemotherapy or hormonal therapy until disease progression. The overall responses of all the patients were assessed as follows: complete response (n = 5), partial response (n = 36), stable disease (n = 24), and progressive disease (n = 31).</p><p><strong>Results: </strong>Immunohistochemistry (IHC) staining was carried out to identify CTMP expression in formalin-fixed paraffin-embedded (FFPE) archival tissue blocks. 58 cases had high CTMP expression levels and 38 cases had low CTMP expression levels. The Mann-Whitney U test showed that CTMP expression was markedly higher in trastuzumab non-responders than in trastuzumab responders (P = 0.039). In addition, high CTMP expression was a strong and independent predictor of shorter recurrence-free survival in patients with metastatic breast cancer, as determined by the Kaplan-Meier method.</p><p><strong>Conclusions: </strong>Based on the results, further examination of CTMP in HER2-enriched (MBC) tissue samples could be helpful in predicting patients at risk of tumor progression and trastuzumab resistance.</p>","PeriodicalId":11148,"journal":{"name":"Discover. Oncology","volume":"16 1","pages":"1342"},"PeriodicalIF":2.8,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12267711/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144642057","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":"A rare case of HER2-positive pure metaplastic squamous cell carcinoma of the breast.","authors":"Lingping Xie, Tianhai Du, Chao Wang","doi":"10.1007/s12672-025-03107-9","DOIUrl":"10.1007/s12672-025-03107-9","url":null,"abstract":"<p><p>Primary squamous cell carcinoma of the breast (PSCCB) is a rare form of metaplastic breast carcinoma (MpBC), constituting approximately 0.1% of all invasive breast cancers. It is characterized by unique morphological and clinical features, exhibiting a high degree of invasiveness and a poor prognosis. Most molecular subtypes are negative for estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2), while HER2-positive PSCCB is even rarer, accounting for approximately 4-22% of cases. Accurate histological diagnosis is crucial for effective management.Currently, there is limited research on neoadjuvant chemotherapy combined with targeted therapy for HER2-positive PSCCB, and standardized treatment protocols have yet to be established. We report a case of pure HER2-positive PSCCB with the aim of gaining experience in the treatment of HER2-positive PSCCB.</p>","PeriodicalId":11148,"journal":{"name":"Discover. Oncology","volume":"16 1","pages":"1340"},"PeriodicalIF":2.8,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12263529/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144642052","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":"Advances in the treatment of malignant tumors with neurological drugs.","authors":"Yongnian Li, Jintong Na, Liping Zhong, Yongxiang Zhao","doi":"10.1007/s12672-025-03013-0","DOIUrl":"10.1007/s12672-025-03013-0","url":null,"abstract":"<p><p>The nervous system governs the body's components and is essential for the physiological functions of all organ systems. The nervous system governs how the body senses, processes, and responds to its environment. Through a complex network of neurons and supporting cells, it connects sensory organs with the brain and spinal cord, and coordinates communication with target organs and tissues throughout the body. This integration of sensory, motor, autonomic, and endocrine functions makes the nervous system essential for maintaining homeostasis and systemic coordination.Consequently, it is anticipated that the nervous system exerts parallel regulatory influences on cancer. Over the past decade, studies have demonstrated a reciprocal relationship between the nervous system and cancer. Taking gliomas, prostate cancer, and breast cancer as examples, where specific nerve types (parasympathetic, sympathetic, or sensory) directly or indirectly control the initiation, progression, and metastasis of cancer. Similarly, cancer can reshape and hijack the structure and function of the nervous system. Chemotherapy has traditionally been the primary and most effective antitumor treatment, while the discovery of neuro-tumor interactions unveils novel strategies for repurposing neuroactive agents as adjuncts to this conventional therapeutic approach. This review elucidates cancer neuroscience through the examples of gliomas, prostate cancer, and breast cancer. Structured around key neuropharmacological receptors, the review systematically explores the potential applications of neuroactive agents and their targets across a broad spectrum of cancer therapies.</p>","PeriodicalId":11148,"journal":{"name":"Discover. Oncology","volume":"16 1","pages":"1346"},"PeriodicalIF":2.8,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12267771/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144642053","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":"Natural killer cell therapy in hepatocellular carcinoma: a comprehensive review.","authors":"Shirin Tavakoli, Maryam Samareh-Salavati, Mahshid Akhavan Rahnama, Shahrokh Abdolahi, Ali Hassanzadeh, Zeinab Ghazvinian, Javad Verdi, Nasim Vousooghi, Saba Manoochehrabadi, Bahram Chahardouli, Maryam Barkhordar, Iman Seyhoun, Mohammad Ahmadvand","doi":"10.1007/s12672-025-03138-2","DOIUrl":"10.1007/s12672-025-03138-2","url":null,"abstract":"<p><p>Hepatocellular carcinoma remains a major healthcare burden worldwide and is predicted to be the cause of death of 1.3 million people in 2040. Most HCC patients are diagnosed in advanced stages, leading to a poor prognosis. The development of targeted immunotherapies is essential to address this unmet clinical challenge. Natural killer (NK) cells have emerged as a promising cell-based therapeutic approach for treating solid tumors. NK cells have the distinctive ability to identify and destroy cancer cells without requiring prior sensitization. Here, we discuss potential approaches, developing strategies, and current challenges of NK cell therapy reported completely. In addition, advancements in immunotherapy, including adoptive NK cell therapy, and the strategies to boost NK cell function against HCC such as cytokine-based treatments, immune checkpoint inhibitors, vaccine-based approaches, genetic delivery, non-coding RNAs, antibody-based methods, and natural agents have been discussed. This comprehensive study provides a unique perspective by integrating recent findings on the differential impact of NK cells on HCC. We highlight the latest advances in NK cell engineering and immune checkpoint modulation, presenting a comparative analysis of therapeutic strategies. Furthermore, we critically assess the translational challenges associated with NK cell-based therapies, particularly focusing on their limited in vivo persistence and tumor immune evasion strategies.</p>","PeriodicalId":11148,"journal":{"name":"Discover. Oncology","volume":"16 1","pages":"1348"},"PeriodicalIF":2.8,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12267803/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144642061","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":"Calcium ion-binding genes can predict tumor mutation burden and immune checkpoint blockade response in a pan-cancer model.","authors":"Wan-Yu Lin, Chien-Jung Huang, Yu-Chao Wang","doi":"10.1007/s12672-025-03184-w","DOIUrl":"10.1007/s12672-025-03184-w","url":null,"abstract":"<p><strong>Background: </strong>Tumor mutation burden (TMB), the total number of nonsynonymous mutations in the tumor genome, is a well-established biomarker for predicting responses to immune checkpoint blockade (ICB) therapy across various cancers. Patients with high TMB tend to exhibit better responses to ICB. Recently, targeted gene panels have been developed to estimate TMB before treatment. These panels are enriched for calcium ion-binding genes. However, a direct link between TMB and calcium ion-binding genes has not been reported in the literature to date.</p><p><strong>Methods: </strong>The association between TMB and calcium ion-binding genes was analyzed using mutation data from The Cancer Genome Atlas (TCGA) database. In addition, a pan-cancer model was constructed to estimate TMB based solely on calcium ion-binding genes. The model's predictive power for ICB response was validated using independent datasets. Finally, enrichment analysis was performed to investigate the biological connections between calcium ion-binding genes and TMB.</p><p><strong>Results: </strong>Calcium ion-binding genes were enriched among the TMB-predictive model genes in 27 out of 33 cancer types. Among these, 19 cancer types exhibited strong predictive performance, with R² values greater than 0.5 in our pan-cancer model based on calcium ion-binding genes. The model effectively estimated TMB and identified ICB responders in independent datasets, including lung adenocarcinoma and melanoma. Enrichment analysis further suggested that calcium ion-binding genes may influence TMB through signal transduction pathways.</p><p><strong>Conclusions: </strong>These findings establish a novel association between calcium ion-binding genes and TMB, demonstrating the feasibility of a pan-cancer TMB estimation model based on calcium ion-binding genes. This approach may enhance TMB estimation and improve ICB response prediction across multiple cancers.</p>","PeriodicalId":11148,"journal":{"name":"Discover. Oncology","volume":"16 1","pages":"1341"},"PeriodicalIF":2.8,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12267738/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144642054","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}