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

Lixia Xu; Shu Chen; Qiaoqiao Li; Xinyi Chen; Yuan Xu; Yongjian Zhou; Juan Li; Zhixian Guo; Jiyuan Xing; Di Chen

doi:10.1186/s12935-023-03208-x

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

Cancer Cell Int. 2024 Jan 13;24(1):30. doi: 10.1186/s12935-023-03208-x.

Authors

Lixia Xu^#¹, Shu Chen^#², Qiaoqiao Li^#³, Xinyi Chen¹, Yuan Xu⁴, Yongjian Zhou¹, Juan Li¹, Zhixian Guo⁵, Jiyuan Xing⁶, Di Chen⁷

Affiliations

¹ Department of Infectious Diseases, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, 450052, China.
² School of Basic Medical Sciences, Xinxiang Medical University, Xinxiang, Henan, 453003, China.
³ The Second Affiliated Hospital of Chongqing Medical University, No. 76 Linjiang Road, Chongqing, 400010, China.
⁴ The First Clinical Medical College, Gannan Medical University, Ganzhou, Jiangxi, 341000, China.
⁵ Department of Infectious Diseases, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, 450052, China. zx_g2764@163.com.
⁶ Department of Infectious Diseases, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, 450052, China. X18137370131@163.com.
⁷ Department of Neurosurgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, 450052, China. mrdichen@163.com.

^# Contributed equally.

Abstract

Background: Hepatocellular 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.

Methods: The 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).

Results: We 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.

Conclusions: The 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.

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

Abstract

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