OncoTargets and therapy最新文献

{"title":"Validation of a Combined Prognostic Score Using Plasma Tumor DNA and Clinical Features in Metastatic Castration-Resistant Prostate Cancer Patients Treated with Taxanes.","authors":"Nicole Brighi, Giuseppe Schepisi, Vincenza Conteduca, Emanuela Scarpi, Paola Caroli, Federica Matteucci, Cristian Lolli","doi":"10.2147/OTT.S509285","DOIUrl":"https://doi.org/10.2147/OTT.S509285","url":null,"abstract":"<p><strong>Purpose: </strong>There is an urgent need of biomarkers to personalize metastatic castration-resistant prostate cancer (mCRPC) treatment. A new prognostic model described by our group combines molecular characteristics (ptDNA levels), metabolic features from PET-scans (metabolic tumor volume), clinical parameters (visceral metastases), and lab tests (lactate-dehydrogenase levels) in abiraterone or enzalutamide-treated patients. This study aims to validate the score on mCRPC patients undergoing taxane treatment.</p><p><strong>Patients and methods: </strong>Twenty-eight patients affected by mCRPC, pre-treated with abiraterone or enzalutamide, candidate for taxane-based treatments, have been prospectively evaluated. All patients underwent a basal PET/CT scan with F-choline and blood samples. The prognostic model previously described was applied to this population; based on the partial results of the parameters, we assigned the patients into three risk groups.</p><p><strong>Results: </strong>In the 28 patients evaluated, we observed a different median OS among the three risk groups (risk group I, 18.1 months [95% CI: 15.2-33.1 months]; risk group II, 12.7 months [4.9-18.6 months]; and risk group III, 10.1 months [3.4-15.4 months]; p = 0.012). Statistically significant differences were also observed for PFS.</p><p><strong>Conclusion: </strong>The prognostic score has confirmed to be a good prognostic tool also in a more advanced cohort of patients treated with taxanes. This tool may represent a valid method to refine prognostication and treatment selection in a cohort of patients where biomarkers are scarce.</p>","PeriodicalId":19534,"journal":{"name":"OncoTargets and therapy","volume":"18 ","pages":"667-677"},"PeriodicalIF":2.7,"publicationDate":"2025-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12117575/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144174358","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":"CXCL11: A Novel Biomarker in Colorectal Cancer as Metastasis Predictor.","authors":"Riyadi Wibowo, Yunia Sribudiani, Kiki Lukman, Reno Rudiman, Tommy Ruchimat, Bambang Am Am Setya Sulthana, Andriana Purnama, Alma Wijaya, Etis Primastari, Prapanca Nugraha","doi":"10.2147/OTT.S515119","DOIUrl":"10.2147/OTT.S515119","url":null,"abstract":"<p><strong>Objective: </strong>CXCL11 (C-X-C motif chemokine ligand 11) encodes a chemokine, a small signaling protein involved in immune and inflammatory responses. This study aims to evaluate the association between CXCL11 gene expression variations and metastasis in colorectal cancer (CRC) patients, highlighting its potential as a biomarker for metastasis.</p><p><strong>Methods: </strong>This is observational laboratory-based study utilized tissue samples from colorectal cancer (CRC) patients stored in the Tissue Bank of the Research Unit, Division of Digestive Surgery, Faculty of Medicine, Universitas Padjadjaran. Conducted between January and August 2024, data collection involved pathological and anatomical assessments of tissue samples obtained through biopsies or tumor resections. Gene expression analysis was performed on 60 fresh tumor tissues using PCR at the Biomolecular Laboratory, Faculty of Medicine, Universitas Padjadjaran.</p><p><strong>Results: </strong>The findings revealed a significant variation in CXCL11 expression among CRC patients based on cancer stage (P = 0.015) and metastasis status (P = 0.017). However, no significant differences in CXCL11 expression were observed concerning age, gender, anatomical pathology, or tumor location.</p><p><strong>Conclusion: </strong>This study identifies a relationship between CXCL11 gene expression differences and metastasis in CRC patients. Further studies with larger sample sizes are recommended to validate CXCL11's role as a biomarker for CRC metastasis. Additionally, future research should explore the potential application of CXCL11 in antitumor therapy.</p>","PeriodicalId":19534,"journal":{"name":"OncoTargets and therapy","volume":"18 ","pages":"657-665"},"PeriodicalIF":2.7,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12085893/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144094486","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 of Residual Axillary Lymph Node Macrometastasis in Early Breast Cancer PATIENTS with One Positive Macrometastasis Sentinel Lymph Node.","authors":"Dao-Yong Liu, Yun Zhu, Qiang Xie, Jun Deng, Bang-Ling Chen","doi":"10.2147/OTT.S506778","DOIUrl":"10.2147/OTT.S506778","url":null,"abstract":"<p><strong>Objective: </strong>To investigate the risk factors for residual axillary lymph node macro-metastasis in early-stage breast cancer patients with a single macrometastasis sentinel lymph node (SLN).</p><p><strong>Methods: </strong>We retrospectively analyzed the clinical data of 119 breast cancer patients diagnosed between January 2018 and September 2023, each with one positive SLN stained with methylene blue, who subsequently underwent axillary lymph node dissection. The patients were divided into two groups based on the total number of SLNs identified: fewer than three and more than three. Fisher's exact test was used for statistical analysis between groups.</p><p><strong>Results: </strong>Among the 119 patients evaluated, 30 patients had a total of 2 sentinel lymph nodes, with 15 testing positive for residual axillary lymph nodes, yielding a positivity rate of 50.0%. Another 30 patients had 3 sentinel lymph nodes, with a positivity rate of 33.3%. An additional 32 patients each had 4 sentinel lymph nodes, with a positivity rate of 3.13%. Finally, 27 patients had 5 sentinel lymph nodes, with a 0% positivity rate. The positivity rate of axillary lymph nodes was significantly higher in the group with ≤ 3 sentinel lymph nodes (less SLN group) compared to the group with > 4 sentinel lymph nodes (more SLN group). Binary logistic regression analysis confirmed that the number of SLNs was the only significant predictor of residual lymph node macrometastasis.</p><p><strong>Conclusion: </strong>The number of sentinel lymph nodes (SLNs) is a key factor influencing the risk of residual axillary lymph node macrometastasis in early-stage breast cancer patients with one positive SLN. Identifying a higher number of SLNs (≥4) significantly lowers the risk of residual metastasis, supporting the use of thorough SLN mapping in these cases to improve patient outcomes.</p>","PeriodicalId":19534,"journal":{"name":"OncoTargets and therapy","volume":"18 ","pages":"647-656"},"PeriodicalIF":2.7,"publicationDate":"2025-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12084877/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144094487","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":"lncSLERT Promotes Liver Metastasis in Colorectal Cancer by Down-Regulating HUNK Expression via RBM15-Mediated m6A Modification.","authors":"Lin Wang, Liming Zhao, Jialiang Liu, Pu Cheng, Mingyu Han, Zhaoxu Zheng","doi":"10.2147/OTT.S514001","DOIUrl":"https://doi.org/10.2147/OTT.S514001","url":null,"abstract":"<p><strong>Background: </strong>Metastasis is a hallmark of cancer and the leading cause of cancer-related mortality. However, the mechanism underlying liver metastasis in colorectal cancer (CRC) remains incompletely understood. This study explores the role of long non-coding RNA (lncRNA) SLERT in promoting CRC liver metastasis by downregulating HUNK expression.</p><p><strong>Methods: </strong>SLERT expression levels in CRC tissues were analyzed and correlated with patient survival outcomes. Functional assays, including migration and invasion assays, were performed to assess the impact of SLERT knockdown and overexpression on metastatic behavior. Mechanistic studies examined SLERT's interaction with the RNA-binding protein RBM15 and its effect on HUNK mRNA stability. The subcellular localization of SLERT was also determined.</p><p><strong>Results: </strong>SLERT was significantly upregulated in CRC tissues and associated with poor survival outcomes. Silencing SLERT inhibited CRC cell migration and invasion, whereas its overexpression enhanced these metastatic properties. Mechanistically, SLERT interacted with RBM15, impairing its ability to stabilize HUNK mRNA, leading to decreased HUNK expression and increased metastatic potential. SLERT was primarily localized in the cytoplasm, indicating its active role in gene regulation within the tumor microenvironment.</p><p><strong>Conclusion: </strong>LERT promotes liver metastasis in CRC by downregulating HUNK expression through RBM15-mediated mRNA destabilization. These findings suggest that SLERT could serve as a diagnostic biomarker and therapeutic target. Targeting SLERT or restoring HUNK expression may provide novel strategies to combat CRC liver metastasis and improve patient prognosis.</p>","PeriodicalId":19534,"journal":{"name":"OncoTargets and therapy","volume":"18 ","pages":"631-646"},"PeriodicalIF":2.7,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12075449/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144079361","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":"Targeting the Inactive Conformation of the Epidermal Growth Factor Receptor Identifies EG31: A Novel Small Molecule Inhibitor Effective Against Normal and 5-Fluorouracil-Resistant Triple Negative Breast Cancer Cells.","authors":"Hassan M Otifi","doi":"10.2147/OTT.S512184","DOIUrl":"https://doi.org/10.2147/OTT.S512184","url":null,"abstract":"<p><strong>Background: </strong>Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer characterized by the absence of estrogen, progesterone, and HER2 receptors, making it difficult to treat with targeted therapies. The Epidermal Growth Factor Receptor (EGFR) is overexpressed in TNBC and is crucial in promoting tumor growth and survival. Despite chemotherapeutics like 5-fluorouracil (5-FU), resistance remains a clinical challenge, underscoring the need for novel therapeutic strategies.</p><p><strong>Methods: </strong>High-throughput virtual screening (HTVS) was employed to identify inhibitors targeting the inactive conformation of EGFR. The top-ranked compounds underwent molecular dynamics (MD) simulations and binding free energy calculations using Molecular Mechanics Poisson-Boltzmann Surface Area (MMPBSA). MDA-MB-231, Hs578T, and 5-FU resistant- MDA-MB-231/5-FU^R cells were utilized to assess the anti-proliferative, EGFR, and apoptosis.</p><p><strong>Results: </strong>HTVS identified EG31 showing strong binding affinities towards EGFR. MD simulations confirmed the stable binding of EG31 to EGFR, as indicated by consistent Root Mean Square Deviation and hydrogen bond patterns throughout the simulation. MMPBSA calculations revealed highly favorable binding free energies. EG31 inhibited MDA-MB-231 and Hs578T proliferations with GI₅₀ values of 498.90 nM and 740.73 nM, respectively. The compound decreased EGFR-positive populations and favored early and late-phase apoptosis in these cells. Furthermore, EG31 retained the anti-proliferative efficacy in the MDA-MB-231/5-FU^R cells, while 5-FU lost its effectiveness by 6-fold.</p><p><strong>Conclusion: </strong>This study identified EG31 targeting the inactive conformation of EGFR, offering a promising therapeutic approach to overcome 5-FU resistance in TNBC. Further research could enhance treatment efficacy and provide a new avenue for managing this challenging cancer subtype.</p>","PeriodicalId":19534,"journal":{"name":"OncoTargets and therapy","volume":"18 ","pages":"617-629"},"PeriodicalIF":2.7,"publicationDate":"2025-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12067978/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144032792","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":"Measles Virus-Based Genetic Modifications: Progress in Hematological Malignancy Treatment.","authors":"Siqian Lan, Zhengyan Zhao, Zhixu He","doi":"10.2147/OTT.S518407","DOIUrl":"https://doi.org/10.2147/OTT.S518407","url":null,"abstract":"<p><p>With the enhancement of public living standards and health awareness, demands for high-quality treatment with hematological malignancies are increasing, correspondingly. However, since significant adverse events have been found associated with chemotherapy, radiotherapy and other traditional anticancer measures, and a considerable number of patients still experience relapse or drug resistance, developing new treatment strategies has become the focus in the field of hematological malignancies. The measles virus vaccine strain, as an oncolytic virus, has been paid special attention to, due to its dual advantages of selectively invading and killing tumor cells and activating anti-tumor immunity. Currently, multiple studies have shown the effectiveness of unmodified measles virus vaccine strains in treating hematological malignancies. However, due to the systemic invasiveness and complexity of hematological malignancies, the concept of genetically engineered measles virus vaccine strain has garnered significant attention. In this article, we reviewed the progress on measles virus vaccine strains in the treatment of hematological malignancies, especially on the application of genetic engineering technology. Meanwhile, we also explored the challenges encountered in current treatments and discussed future design direction for modifying measles virus vaccine strains.</p>","PeriodicalId":19534,"journal":{"name":"OncoTargets and therapy","volume":"18 ","pages":"605-615"},"PeriodicalIF":2.7,"publicationDate":"2025-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12039834/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143984487","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":"Erratum: Efficacy and Safety of Combined PD-1 Inhibitor with Induction Chemotherapy Followed by IMRT Plus Nimotuzumab in Locally Advanced Nasopharyngeal Carcinoma: A Retrospective Analysis [Corrigendum].","authors":"","doi":"10.2147/OTT.S533353","DOIUrl":"https://doi.org/10.2147/OTT.S533353","url":null,"abstract":"<p><p>[This corrects the article DOI: 10.2147/OTT.S503674.].</p>","PeriodicalId":19534,"journal":{"name":"OncoTargets and therapy","volume":"18 ","pages":"603-604"},"PeriodicalIF":2.7,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12036795/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143984822","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":"Therapeutic Potential of Datopotamab Deruxtecan in the Treatment of Advanced Non-Small Cell Lung Cancer: Evidence to Date.","authors":"Maya Gogtay, Nikhila Aimalla, Ram Prakash Thirugnanasambandam, Apar Kishor Ganti","doi":"10.2147/OTT.S466220","DOIUrl":"https://doi.org/10.2147/OTT.S466220","url":null,"abstract":"<p><p>Lung cancer is the leading cause of global cancer mortality, accounting for an estimated 2 million diagnoses and 1.8 million deaths annually. Treatment choices for non-small cell lung cancer include surgery, radiation therapy, chemotherapy, immunotherapy, or molecularly targeted therapy. Antibody-drug conjugates (ADCs), often likened to \"biological missiles\", are rapidly evolving as a targeted therapeutic approach. Trophoblast cell surface antigen 2 (Trop 2) is a 36-kDa cell surface glycoprotein, which is expressed in various cancers. This fuels oncogenic signaling pathways, driving tumor advancement, invasion, and spread. Its limited expression in healthy human tissues underscores its potential as a target for cancer treatment. Datopotamab Deruxtecan (Dato-Dxd) is an investigational ADC that targets Trop-2. This review discusses the current treatment landscape involving therapy with Dato-Dxd for advanced NSCLC. Dato-DXd was first used in metastatic solid tumors in the Phase I TROPION-PanTumor 01 trial, which showed promising antitumor activity in the previously pretreated NSCLC cohort and a manageable safety outline. In TROPION-Lung01, Dato-DXD was studied in metastatic NSCLC patients who were previously treated and showed an objective response rate of 26.4% (Dato-DXd). Other trials, including TROPION PanTumor 02, ICARUS - Lung 01, and TROPION Lung 05, showed comparable results. Dato-DXd used along with pembrolizumab, with or without systemic chemotherapy, in TROPION Lung 02 with promising efficacy results. The most common any-grade treatment-emergent adverse events were stomatitis, nausea, and hair loss, mostly grade 1-2. There are several clinical trials in the pipeline using Dato-DXd in the front-line metastatic setting and resectable NSCLC patients. Dato-DXd is currently pending approval from the US Food and Drug Administration (FDA). If approved, datopotamab deruxtecan will be the first TROP2-directed antibody-drug conjugate for non-small cell lung cancer.</p>","PeriodicalId":19534,"journal":{"name":"OncoTargets and therapy","volume":"18 ","pages":"575-584"},"PeriodicalIF":2.7,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12034271/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144040354","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 Pyroptosis-Related LncRNA Signature for Predicting Prognosis, Immune Features and Drug Sensitivity in Ovarian Cancer.","authors":"Po-Wu Liu, Zhao-Yi Liu, Shi-Jia Deng, Xiu Zhang, Zhi-Bin Wang, Na-Yiyuan Wu, Chao-Shui Liu, Ming-Hua Hu, Jing Wang, He Li","doi":"10.2147/OTT.S491130","DOIUrl":"https://doi.org/10.2147/OTT.S491130","url":null,"abstract":"<p><strong>Background: </strong>Multiple studies have suggested that lncRNAs and pyroptosis play important roles in ovarian cancer (OC). However, the function of pyroptosis-related lncRNAs (PRLs) in OC is not fully understood.</p><p><strong>Methods: </strong>Clinical information and RNA-seq data of OC patients (n = 379) were collected from TCGA database. Pearson correlation analysis and univariate Cox analysis were performed to identify prognostic PRLs, respectively. LASSO-COX regression was utilized to construct a prognostic PRLs signature. Kaplan-Meier (K-M) curve analyses and receiver operating characteristics (ROC) were used to evaluate the prognostic prediction of the signature. The association between risk score and tumor microenvironment infiltration, immunotherapy response and chemotherapy sensitivity were also analyzed. In addition, the function of TYMSOS on OC and pyroptosis was experimentally confirmed in cell lines.</p><p><strong>Results: </strong>Firstly, 32 prognostic PRLs were identified, and a novel prognostic PRLs signature was constructed and validated. Surprisingly, the prognostic PRLs signature could solidly predict the clinical outcome of patients with OC and patients with high-risk score shown a short overall survival. GSEA results suggested that the RPLs were mainly enriched in the inflammatory response pathway, p53 pathway, TGF-β signaling and TNFα signaling. Besides, our results demonstrated that the risk score was significantly associated with patients with immune infiltration, immunotherapy response and the sensitivity of veliparib and metformin. Furthermore, the oncogene effect of TYMSOS on OC by inhibiting pyroptosis was verified by experiments.</p><p><strong>Conclusion: </strong>This study found that the prognostic PRLs signature may serve as an efficient biomarker in predicting the prognosis, tumor microenvironment infiltration, and sensitivity of chemotherapeutic agents. TYMSOS is a potential biomarker in OC, and it might promote tumor progression by inhibiting pyroptosis.</p>","PeriodicalId":19534,"journal":{"name":"OncoTargets and therapy","volume":"18 ","pages":"585-601"},"PeriodicalIF":2.7,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12034292/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144035188","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":"Based on Soluble Immune Checkpoints Constructing a Random Survival Forest Model to Predict the Prognosis of Hepatitis B Virus-Associated Hepatocellular Carcinoma.","authors":"Xue Cai, Lihua Yu, Xiaoli Liu, Huiwen Yan, Yuqing Xie, Qing Pu, Zimeng Shang, Yuan Wu, Tingting Jiang, Zhiyun Yang","doi":"10.2147/OTT.S512838","DOIUrl":"https://doi.org/10.2147/OTT.S512838","url":null,"abstract":"<p><strong>Background: </strong>Nowadays, immune checkpoint blockade (ICB) therapy has become a milestone in immunotherapy for hepatocellular carcinoma (HCC). However, its clinical effectiveness remains low. Soluble (s) immune checkpoints (ICs), functional components of membrane ICs, are novel physiological immunomodulators. We investigated the prognostic value of sICs in patients of hepatitis B virus-associated hepatocellular carcinoma (HBV-HCC) and provided clinical clues for potential new targets for future immunotherapy.</p><p><strong>Methods: </strong>A total of 256 participants were included in this study. We compared the plasma levels of 14 sICs in healthy controls (HC), chronic hepatitis B (CHB), hepatitis B-related liver cirrhosis (HBV-LC), and HBV-HCC groups. COX and random survival forest (RSF) were used to select variables and construct a model to predict overall survival of patients with HBV-HCC. We evaluated the predictive efficacy and analyzed the correlations between sICs, clinical parameters, and membrane ICs.</p><p><strong>Results: </strong>The levels of 14 sICs in HBV-HCC were elevated compared to that in HC. The areas under the receiver operating characteristic values of 1-, 2-, and 3-year survival predicted by the RSF model were 0.96, 0.85, and 0.81 in the training set, and 0.91, 0.80, and 0.71 in the validation set. The model could adapt to different event distributions and clinical staging systems. Soluble glucocorticoid-induced tumor necrosis factor receptor (sGITR), soluble programmed cell death-ligand 1 (sPD-L1) and soluble T cell immunoglobulin and mucin domain-containing protein 3 (sTIM-3) were closely associated with the prognosis of patients. Soluble PD-L1 was negatively correlated with HGB and positively correlated with AST and NLR (<i>P</i> < 0.05). Soluble TIM-3 was negatively correlated with ALB and CD8+ T cells and positively correlated with HBV-DNA, AST, LDH and mTIM-3 expression in CD8+ T cells (<i>P</i><0.05).</p><p><strong>Conclusion: </strong>We constructed a predictive model based on sICs to predict different survival times in HBV-HCC patients. The risk stratification effectively identified potentially critical patients. Soluble GITR, sPD-L1 and sTIM-3 were important immunological indicators which could dynamically monitor patients' immune status.</p>","PeriodicalId":19534,"journal":{"name":"OncoTargets and therapy","volume":"18 ","pages":"559-573"},"PeriodicalIF":2.7,"publicationDate":"2025-04-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12020021/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144030880","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}