Integrating bioinformatics and experimental validation to unveil disulfidptosis-related lncRNAs as prognostic biomarker and therapeutic target in hepatocellular carcinoma

作者全名："Xu, Lixia; Chen, Shu; Li, Qiaoqiao; Chen, Xinyi; Xu, Yuan; Zhou, Yongjian; Li, Juan; Guo, Zhixian; Xing, Jiyuan; Chen, Di"

作者地址："[Xu, Lixia; Chen, Xinyi; Zhou, Yongjian; Li, Juan; Guo, Zhixian; Xing, Jiyuan] Zhengzhou Univ, Affiliated Hosp 1, Dept Infect Dis, Zhengzhou 450052, Henan, Peoples R China; [Chen, Shu] Xinxiang Med Univ, Sch Basic Med Sci, Xinxiang 453003, Henan, Peoples R China; [Li, Qiaoqiao] Chongqing Med Univ, Affiliated Hosp 2, Dept Ophthalmol, 76 Linjiang Rd, Chongqing 400010, Peoples R China; [Xu, Yuan] Gannan Med Univ, Clin Med Coll 1, Ganzhou 341000, Jiangxi, Peoples R China; [Chen, Di] Zhengzhou Univ, Affiliated Hosp 1, Dept Neurosurg, Zhengzhou 450052, Henan, Peoples R China"

通信作者："Guo, ZX; Xing, JY (通讯作者)，Zhengzhou Univ, Affiliated Hosp 1, Dept Infect Dis, Zhengzhou 450052, Henan, Peoples R China.; Chen, D (通讯作者)，Zhengzhou Univ, Affiliated Hosp 1, Dept Neurosurg, Zhengzhou 450052, Henan, Peoples R China."

来源：CANCER CELL INTERNATIONAL

ESI学科分类：MOLECULAR BIOLOGY & GENETICS

WOS号：WOS:001142062700003

JCR分区：Q1

影响因子：5.8

年份：2024

卷号：24

期号：1

开始页：　

结束页：　

文献类型：Article

关键词：Disulfidptosis; Long non-coding RNA; Hepatocellular carcinoma; Prognostic signature; Immune microenvironment; TMCC1-AS1

摘要："BackgroundHepatocellular carcinoma (HCC) stands as a prevalent malignancy globally, characterized by significant morbidity and mortality. Despite continuous advancements in the treatment of HCC, the prognosis of patients with this cancer remains unsatisfactory. This study aims at constructing a disulfidoptosis-related long noncoding RNA (lncRNA) signature to probe the prognosis and personalized treatment of patients with HCC.MethodsThe data of patients with HCC were extracted from The Cancer Genome Atlas (TCGA) databases. Univariate, multivariate, and least absolute selection operator Cox regression analyses were performed to build a disulfidptosis-related lncRNAs (DRLs) signature. Kaplan-Meier plots were used to evaluate the prognosis of the patients with HCC. Functional enrichment analysis was used to identify key DRLs-associated signaling pathways. Spearman's rank correlation was used to elucidate the association between the DRLs signature and immune microenvironment. The function of TMCC1-AS1 in HCC was validated in two HCC cell lines (HEP3B and HEPG2).ResultsWe identified 11 prognostic DRLs from the TCGA dataset, three of which were selected to construct the prognostic signature of DRLs. We found that the survival time of low-risk patients was considerably longer than that of high-risk patients. We further observed that the composition and the function of immune cell subpopulations were significantly different between high- and low-risk groups. Additionally, we identified that sorafenib, 5-Fluorouracil, and doxorubicin displayed better responses in the low-score group than those in the high-score group, based on IC50 values. Finally, we confirmed that inhibition of TMCC1-AS1 impeded the proliferation, migration, and invasion of hepatocellular carcinoma cells.ConclusionsThe DRL signatures have been shown to be a reliable prognostic and treatment response indicator in HCC patients. TMCC1-AS1 showed potential as a novel prognostic biomarker and therapeutic target for HCC."

基金机构：Henan Medical Science and Technology Joint Building Program

基金资助正文：Not applicable.