OncoTargets and therapy最新文献

{"title":"Crosstalk of <i>SPINK4</i> Expression With Patient Mortality, Immunotherapy and Metastasis in Pan-Cancer Based on Integrated Multi-Omics Analyses.","authors":"Xiuhua Cao, Na Luo, Xiaoyan Liu, Kan Guo, Mingming Deng, Chaoxiang Lv","doi":"10.2147/OTT.S487126","DOIUrl":"10.2147/OTT.S487126","url":null,"abstract":"<p><strong>Background: </strong>Cancer remains a major global health challenge, with early detection and prompt treatment being crucial for reducing mortality rates. The <i>SPINK4</i> has been linked to the development of several tumors, and there is growing evidence of its involvement. However, its specific functions and effects in different cancer types remain unclear.</p><p><strong>Methods: </strong>The association between <i>SPINK4</i> expression levels and tumor progression was investigated and confirmed using the TCGA dataset. Kaplan-Meier curves were utilized to examine the correlation between <i>SPINK4</i> expression with survival outcomes in pan-cancer patients. The Pearson method was employed to investigate the association of <i>SPINK4</i> expression with the tumor microenvironment, stemness score, immunoinfiltrating subtype, and chemotherapy sensitivity in human different cancer types. Wound healing and Transwell assays were performed to confirm the roles of the model gene in colon adenocarcinoma cells.</p><p><strong>Results: </strong>The expression of <i>SPINK4</i> shows heterogeneity across pan-cancer tissues, and is closely associated with poor prognosis, immune cell invasion, tumor cell resistance, and tumor metastasis in a various human cancer. Mutation of <i>SPINK4</i> hold significant predictive value for poor prognosis of pan-cancer patients. In addition, <i>SPINK4</i> expression was significantly correlated with the tumor microenvironment (stromal cells and immune cells) and stemness score (DNAss and RNAss) in human pan-cancer tissues, particularly in BLCA and COAD. Single-cell sequencing analysis showed that SPINK4 is mainly expressed in endothelial cells in BLCA and in malignant cells in COAD. Drug resistance analysis showed a significant association between <i>SPINK4</i> expression and sensitivity to several cancer chemotherapy drugs. Importantly, overexpression of <i>SPINK4</i> promoted the metastasis of colon cancer cell lines (HCT116 and RKO), whereas <i>SPINK4</i> knockout markedly inhibited their metastasis.</p><p><strong>Conclusion: </strong>These findings reveal the crucial role of <i>SPINK4</i> in the pan-cancer process and may have significant implications for the diagnosis and treatment of cancer in the future.</p>","PeriodicalId":19534,"journal":{"name":"OncoTargets and therapy","volume":"18 ","pages":"161-177"},"PeriodicalIF":2.7,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11806753/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143383032","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":"Dynamic Coupling of MAPK Signaling to the Guanine Nucleotide Exchange Factor GEF-H1.","authors":"Kévin Leguay, Oliver A Kent","doi":"10.2147/OTT.S496228","DOIUrl":"https://doi.org/10.2147/OTT.S496228","url":null,"abstract":"<p><p>The <i>KRAS</i> gene is nearly ubiquitously subjected to activating mutation in pancreatic adenocarcinomas (PDAC), occurring at a frequency of over 90% in tumors. Mutant KRAS drives sustained signaling through the MAPK pathway to affect frequently disrupted cancer phenotypes including transcription, proliferation and cell survival. Recent research has shown that PDAC tumor growth and survival required a guanine nucleotide exchange factor for RAS homolog family member A (RhoA) called GEF-H1. The GEF-H1 protein, encoded by the <i>ARHGEF2</i> gene, is a microtubule-associated GEF for RhoA that promotes invasion-migration of PDAC cells via activation of RhoA. Unexpectedly, independent of its RhoGEF activity, GEF-H1 was found to potentiate MAPK signaling by scaffolding protein phosphatase 2A (PP2A) to the kinase suppressor of Ras 1 (KSR-1). In a feedback-dependent manner, enhanced MAPK activity drives expression of <i>ARHGEF2</i> via regulation of transcription factors ETS and SP, and the RAS responsive element-binding protein 1 (RREB1). RREB1 a negative regulator of <i>ARHGEF2</i> expression, is downregulated in PDAC cells, which permits sustained expression of GEF-H1 for PDAC tumor survival and subsequent MAPK pathway activation. Given that MAPK targeted therapies show limited clinical efficacy, highlights the need for novel targets. This review describes the unexpected complexity of GEF-H1 function leading to positive feedback that potentiates RAS-MAPK signaling and suggests inhibition of GEF-H1 as a therapeutic strategy for RAS-driven cancers.</p>","PeriodicalId":19534,"journal":{"name":"OncoTargets and therapy","volume":"18 ","pages":"147-159"},"PeriodicalIF":2.7,"publicationDate":"2025-01-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11776410/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143066668","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":"Pan-Cancer Analysis Identifies YKT6 as a Prognostic and Immunotherapy Biomarker, with an Emphasis on Cervical Cancer.","authors":"Jiamin Liu, Qiang Zhang, Ling He, Huangyu Hu, Yixuan Wang, Ping Xie","doi":"10.2147/OTT.S491310","DOIUrl":"10.2147/OTT.S491310","url":null,"abstract":"<p><strong>Background: </strong>Soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE)-mediated membrane fusion is crucial for autophagy, making YKT6, a key modulator of cell membrane fusion, a potential target for cancer therapy. However, its oncogenic role across different cancers remains unclear. This study was to investigate the prognostic value and potential immunological functions of YKT6, including cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC).</p><p><strong>Methods: </strong>Multiple bioinformatics databases, including The Cancer Genome Atlas (TCGA), Cancer Cell Line Encyclopedia (CCLE), and Genotype-Tissue Expression (GTEx) databases, were used to investigate the correlation of the YKT6 expression pattern with the pathological stage and survival rate across cancers. Furthermore, ImmuCellAI, the UCSC Xena platform, and the ESTIMATE algorithm were subsequently utilized to explore the potential relationship between YKT6 expression, the tumor microenvironment, and tumor immune infiltration. Profiling of YKT6 gene mutation and amplification, methylation, and copy number alteration (CNA) was performed on the basis of the TCGA database. Moreover, q-PCR, TMA staining, and siRNA assays were used to validate the cancer-promoting role of YKT6 in CESCs.</p><p><strong>Results: </strong>Our results reveal that YKT6 is a potential prognostic and cancer immunity biomarker. Elevated YKT6 expression is correlated with poor overall survival (OS) and disease-free survival (DFS). Distinct gene mutation, methylation, and CNA patterns for YKT6 were found in certain types of cancers. The correlation of YKT6 expression with tumor-infiltrating immune cells was verified by analyzing the StromalScore, ESTIMATEScore, ImmuneScore, and tumor purity. In vitro analysis confirmed that YKT6 was highly expressed in advanced-grade CESCs and that the knockdown of YKT6 inhibited the proliferation of cervical cancer cells.</p><p><strong>Conclusion: </strong>The SNARE protein YKT6 serves as a biomarker and candidate oncogene with actionable mutations. Moreover, YKT6 has the potential to be a prognostic indicator in CESCs. Targeting YKT6 could enhance autophagy regulation and improve therapeutic strategies for personalized cancer treatment.</p>","PeriodicalId":19534,"journal":{"name":"OncoTargets and therapy","volume":"18 ","pages":"107-127"},"PeriodicalIF":2.7,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11766309/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143047404","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":"Exploration and Identification of Vitamin D and Related Genes as Potential Biomarkers for Colorectal Tumors.","authors":"Lu Wang, Ruize Xu, Mizhu Wang, Menghan Wang, Shuai Su, Yuanyuan Nian, Xin Chen","doi":"10.2147/OTT.S495066","DOIUrl":"10.2147/OTT.S495066","url":null,"abstract":"<p><strong>Objective: </strong>To explore the relationship and underlying mechanisms between vitamin D and CRC, offering valuable insights into the diagnosis and treatment of CRC.</p><p><strong>Materials and methods: </strong>Serum levels of 1,25(OH)₂D₃ were measured using a double-antibody sandwich assay. Bioinformatics analysis identified vitamin D-related CRC genes, which were validated using HCT116 and HT29 cell lines. Changes in hub gene expression were analyzed via RT-qPCR.</p><p><strong>Results: </strong>Serum levels of 1,25(OH)₂D₃ were 42.99±6.02µg/mL in the normal group, 37.06±9.56µg/mL in the CRA group, and 19.00±5.96µg/mL in the CRC group (p<0.05). No significant differences were observed in VDR SNPs among the groups. Significant expression differences were detected in vitamin D-related colon cancer genes across the groups. LASSO regression analysis identified 5 key genes. The diagnostic model based on these genes demonstrated high diagnostic efficiency and performed well in the TCGA-COAD dataset. RT-qPCR results showed that SOSTDC1, PRKAA2, and CEACAM1 expressions decreased in the CRC and CRA groups, while MMP1 and CCND1 expressions increased. In vitro experiments indicated that calcitriol inhibits the proliferation and migration of HCT116 and HT29 cell lines and significantly alters the expression of hub genes.</p><p><strong>Conclusion: </strong>Serum vitamin D levels are significantly lower in CRC patients. Vitamin D has been shown to inhibit the proliferation and migration of colon cancer cells and reduce the expression of oncogenes. Therefore, vitamin D holds substantial potential for the diagnosis and treatment of CRC.</p>","PeriodicalId":19534,"journal":{"name":"OncoTargets and therapy","volume":"18 ","pages":"129-145"},"PeriodicalIF":2.7,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11769849/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143053046","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":"Research Progress of NK Cells in Glioblastoma Treatment.","authors":"Hao Wu, Qi Liu, Fenglu Wang, Wenwen Gao, Feng Zhou, Haikang Zhao","doi":"10.2147/OTT.S486411","DOIUrl":"10.2147/OTT.S486411","url":null,"abstract":"<p><p>NK cells are a type of antitumor immune cell with promising clinical application, following T cells. The activity of NK cells is primarily regulated by their surface receptors and immune microenvironment. In gliomas, the tumor microenvironment exerts a strong immunosuppressive effect, which significantly reduces the clinical efficacy of NK cell immunotherapy. Therefore, this review aims to discuss the latest research on the role of NK cells in glioma immunotherapy, focusing on aspects such as NK cell development, function, and localization. It summarizes information on the compounds, monoclonal antibodies, and cytokine therapies targeting NK cells while emphasizing the current status and trends of gene-modified NK cells in glioma treatment. Additionally, it explores the molecular mechanisms underlying immune escape in glioma cells, providing a theoretical foundation and new perspectives for NK cell-based immunotherapy in gliomas.</p>","PeriodicalId":19534,"journal":{"name":"OncoTargets and therapy","volume":"18 ","pages":"87-106"},"PeriodicalIF":2.7,"publicationDate":"2025-01-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11752833/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143024185","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":"Prognostic Value of Pretreatment Carcinoembryonic Antigen (CEA) in Rectal Cancer Treated with Preoperative Short-Course Radiotherapy with Delayed Surgery or Long-Course Radiotherapy.","authors":"Yun-Hsuan Lin, Hsuan-Chih Hsu, Eng-Yen Huang","doi":"10.2147/OTT.S474855","DOIUrl":"10.2147/OTT.S474855","url":null,"abstract":"<p><strong>Purpose: </strong>To investigate the prognostic value of the pretreatment serum carcinoembryonic antigen (CEA) level in patients with rectal cancer treated by preoperative short-course radiotherapy (SCRT) followed by chemotherapy and delayed surgery.</p><p><strong>Patients and methods: </strong>Two hundred and sixty-six consecutive patients with locally advanced rectal adenocarcinoma without distant metastasis receiving preoperative radiotherapy were enrolled. Group 1 patients (n=144) received long-course radiotherapy (LCRT) with 50.4 Gy in 28 fractions using photon radiotherapy (XRT). Group 2 patients (n=122) received SCRT with 25 Gy in 5 fractions using XRT or proton beam therapy (PBT) followed by chemotherapy and delayed surgery. Pathological complete response (pCR), near pathological complete response (npCR), locoregional recurrence (LRR), distant metastasis (DM), disease-specific survival (DSS) and overall survival (OS) rates were estimated and compared to scrutinize the prognostic significance of factors including CEA level.</p><p><strong>Results: </strong>In group 1, higher CEA level (≥ 7 ng/mL) was a significant negative prognostic factor of pCR (<i>p</i> = 0.003, OR: 0.133), OS (<i>p</i> = 0.011, HR: 2.999), DM (<i>p</i> = 0.008, HR: 2.569), LRR (<i>p</i> = 0.044, HR: 3.160), and DSS (<i>p</i> = 0.015, HR: 3.273). In group 2, higher CEA level (≥ 7 ng/mL) was a significant negative prognostic factor of pCR (<i>p</i> = 0.002, OR: 0.038), OS (<i>p</i> < 0.001, HR: 44.658), DM (<i>p</i> < 0.001, HR: 8.926), LRR (<i>p</i> = 0.028, HR: 8.570), and DSS (<i>p</i> = 0.001, HR: 43.918). The npCR rates for clinical T4 patients were 6.5% and 22.0% (<i>p</i> = 0.032), in group 1 and group 2, respectively.</p><p><strong>Conclusion: </strong>This study elucidates the prognostic merit of the pretreatment serum CEA level in patients with rectal cancer treated by either preoperative LCRT or SCRT followed by chemotherapy and delayed surgery.</p>","PeriodicalId":19534,"journal":{"name":"OncoTargets and therapy","volume":"18 ","pages":"73-86"},"PeriodicalIF":2.7,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11748052/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143009146","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":"Roles of SPOCK1 in the Formation Mechanisms and Treatment of Non-Small-Cell Lung Cancer and Brain Metastases from Lung Cancer.","authors":"Xuebing Zhang, Xia Zhang, Hang Yin, Qizheng Li, Buqun Fan, Bolun Jiang, Anqi Xie, Dandan Guo, Huanling Hao, Bin Zhang","doi":"10.2147/OTT.S483576","DOIUrl":"10.2147/OTT.S483576","url":null,"abstract":"<p><p>Lung cancer is a malignant tumor with high morbidity and mortality in China and worldwide. Once it metastasizes to the brain, its prognosis is very poor. Brain metastases are found in about 20% of newly diagnosed non-small-cell lung cancer (NSCLC) patients. About 30% of NSCLC patients develop brain metastases during treatment. NSCLC that is positive for EGFR, ALK, and ROS1 variations is especially likely to metastasize to the brain. SPOCK1 is a proteoglycan with systemic physiological functions. It regulates the self-renewal of brain metastasis-initiating cells, regulates invasion and metastasis from the lung to the brain, plays an important role in tumor progression and treatment resistance, and has higher expression in metastatic tumor tissues than other tissues. Current treatments for NSCLC brain metastases include surgery, whole-brain radiotherapy, stereotactic radiotherapy, targeted therapy, and chemotherapy. SPOCK1 is involved in many signaling pathways, by which it influences a variety of NSCLC treatment methods. In this paper, the progress of research on the treatment of NSCLC brain metastases is reviewed to guide decisions on treatment options in clinical practice.</p>","PeriodicalId":19534,"journal":{"name":"OncoTargets and therapy","volume":"18 ","pages":"35-47"},"PeriodicalIF":2.7,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11745074/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143009048","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":"Integrated Network Pharmacology, Machine Learning and Experimental Validation to Identify the Key Targets and Compounds of <i>TiaoShenGongJian</i> for the Treatment of Breast Cancer.","authors":"Huiyan Ying, Weikaixin Kong, Xiangwei Xu","doi":"10.2147/OTT.S486300","DOIUrl":"10.2147/OTT.S486300","url":null,"abstract":"<p><strong>Background: </strong>TiaoShenGongJian (TSGJ) decoction, a traditional Chinese medicine for breast cancer, has unknown active compounds, targets, and mechanisms. This study identifies TSGJ's key targets and compounds for breast cancer treatment through network pharmacology, machine learning, and experimental validation.</p><p><strong>Methods: </strong>Bioactive components and targets of TSGJ were identified from the TCMSP database, and breast cancer-related targets from GeneCards, PharmGkb, and RNA-seq datasets. Intersection of these targets revealed therapeutic targets of TSGJ. PPI analysis was performed via STRING, and machine learning methods (SVM, RF, GLM, XGBoost) identified key targets, validated by GSE70905, GSE70947, GSE22820, and TCGA-BRCA datasets. Pathway analyses and molecular docking were performed. TSGJ and core compounds' effectiveness was confirmed by MTT and RT-qPCR assays.</p><p><strong>Results: </strong>160 common targets of TSGJ were identified, with 30 hub targets from PPI analysis. Five predictive targets (HIF1A, CASP8, FOS, EGFR, PPARG) were screened via SVM. Their diagnostic, biomarker, immune, and clinical values were validated. Quercetin, luteolin, and baicalein were identified as core components. Molecular docking confirmed their strong affinities with predicted targets. These compounds modulated key targets and induced cytotoxicity in breast cancer cell lines in a similar way as TSGJ.</p><p><strong>Conclusion: </strong>This study reveals the main active components and targets of TSGJ against breast cancer, supporting its potential for breast cancer prevention and treatment.</p>","PeriodicalId":19534,"journal":{"name":"OncoTargets and therapy","volume":"18 ","pages":"49-71"},"PeriodicalIF":2.7,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11745062/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143009144","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 Post-Transplant Lymphoproliferative Disorder Presenting as Hodgkin Lymphoma After Autologous Hematopoietic Stem Cell Transplantation: A Case Report and Literature Review.","authors":"Yuzhan Chen, Ying Chen, Yimin He, Qitian Mu, Guifang Ouyang","doi":"10.2147/OTT.S490591","DOIUrl":"10.2147/OTT.S490591","url":null,"abstract":"<p><p>Post-transplant lymphoproliferative disorder (PTLD) is a rare complication following hematopoietic stem cell transplantation (HSCT), with its occurrence post-autologous hematopoietic stem cell transplantation (auto-HSCT) being even rarer. Research on PTLD following auto-HSCT is exceedingly scarce. Here, we present a noteworthy instance wherein a patient with diffuse large B-cell lymphoma (DLBCL) developed PTLD, manifesting as classical Hodgkin lymphoma (cHL) two years after auto-HSCT. Additionally, we conducted an extensive review of existing literature, exploring the current research on PTLD following auto-HSCT and illuminating this scarcely examined area.</p>","PeriodicalId":19534,"journal":{"name":"OncoTargets and therapy","volume":"18 ","pages":"27-33"},"PeriodicalIF":2.7,"publicationDate":"2025-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11742566/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143009140","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":"High Intelectin-1 Expression Associated with Aggressive Tumor Behavior and Worse Survival in Rectal Cancer.","authors":"Chia-Lin Chou, Cheng-Wei Lin, Wan-Shan Li, Tzu-Ju Chen, Sung-Wei Lee, Yu-Feng Tian, Yu-Hsuan Kuo, Hsin-Hwa Tsai, Li-Ching Wu, Cheng-Fa Yeh, Yow-Ling Shiue, Hong-Yue Lai, Ching-Chieh Yang","doi":"10.2147/OTT.S488608","DOIUrl":"https://doi.org/10.2147/OTT.S488608","url":null,"abstract":"<p><strong>Background: </strong>Multimodal treatment involving preoperative chemoradiotherapy (CRT) followed by surgery is the current standard of care for rectal cancer. Despite advancements, the risk of recurrence, metastasis, and decreased survival remains high. This study aims to evaluate potential biomarkers to stratify prognosis in patients with rectal cancer undergoing preoperative CRT and surgery.</p><p><strong>Methods: </strong>Through data mining of receptor-binding pathways in a published transcriptome for rectal cancer cases, ITLN1 was identified as the most relevant gene associated with poor response to chemoradiation (GO:0005102). Rectal cancer specimens (n = 343) collected between 1998 and 2017 were analyzed for ITLN1 expression using immunohistochemistry. The association between ITLN1 protein expression and clinicopathological features was assessed using Pearson's chi-square test. Survival outcomes based on ITLN1 expression were evaluated using the Kaplan-Meier method and compared with Log rank tests.</p><p><strong>Results: </strong>ITLN1 immunoreactivity was significantly elevated in rectal tumor tissues. High ITLN1 expression was strongly associated with adverse clinicopathological features, including advanced post-treatment tumor status (T3-4; p = 0.001), post-treatment nodal status (N1-2; p < 0.001), vascular invasion (p = 0.017), perineural invasion (p = 0.001), and a lower degree of tumor regression (p = 0.009). Uni- and multivariable analyses revealed that high ITLN1 expression correlated with poorer disease-specific survival, local recurrence-free survival, and distant metastasis-free survival compared to low ITLN1 expression.</p><p><strong>Conclusion: </strong>Elevated ITLN1 expression is significantly associated with aggressive tumor behavior and unfavorable survival outcomes in rectal cancer. These findings highlight ITLN1 as a potential prognostic biomarker and provide a foundation for future research into its role in rectal cancer progression and treatment response.</p>","PeriodicalId":19534,"journal":{"name":"OncoTargets and therapy","volume":"18 ","pages":"15-26"},"PeriodicalIF":2.7,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11740546/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143009142","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}