Identification of a DNA damage repair-related LncRNA signature for predicting the prognosis and immunotherapy response of hepatocellular carcinoma.

Abstract

BACKGROUND:

DNA damage repair (DDR) may affect tumorigenesis and therapeutic response in hepatocellular carcinoma (HCC). Long noncoding RNAs (LncRNAs) can regulate DDR and play a vital role in maintaining genomic stability in cancers. Here, we identified a DDR-related prognostic signature in HCC and explored its potential clinical value.

METHODS:

Data of HCC samples were obtained from the Cancer Genome Atlas (TCGA), and a list of DDR-related genes was extracted from the Molecular Signatures database (MSigDB). A DDR-related lncRNAs signature associated to overall survival (OS) was constructed using the least absolute shrinkage and selection operator-cox regression, and was further validated by the Kaplan-Meier curve and receiver operating characteristic curve. A nomogram integrating other clinical risk factors was established. Moreover, the relationships between the signature with somatic mutation, immune landscape and drug sensitivity were explored.

RESULTS:

The prognostic model of 5 DDR-related lncRNAs was constructed and classified patients into two risk groups at median cut-off. The low-risk group had a better OS, and the signature was an independent prognostic indicator in HCC. A nomogram of the signature combined with TNM stage was constructed. TP53 gene was more frequently mutated in the high-risk group. Marked differences in immune cells were observed, such as CD4 + T cells, NK cells and macrophages, between the two groups. Moreover, an increase in the expression of immune checkpoint molecules was found in the high-risk group. The low-risk group presented with a significantly higher response to sorafenib or cisplatin. Finally, potential value of this signature was validated in real-world HCC patients.

CONCLUSION:

Our findings provided a promising insight into DDR-related lncRNAs in HCC and a personalized prediction tool for prognosis and therapeutic response.

• Authors: Fei Huang, Chunyan Zhang, Wenjing Yang, Yan Zhou, Yihui Yang, Xinrong Yang, Wei Guo, Beili Wang
• Journal: BMC genomics (BMC Genomics) Vol. 25 Issue 1 Pg. 155 (Feb 08 2024) ISSN: 1471-2164 [Electronic] England
• PMID: 38326754 (Publication Type: Journal Article)
• Copyright: © 2024. The Author(s).

Chemical References

• RNA, Long Noncoding

Topics

• Humans
• Carcinoma, Hepatocellular (genetics, therapy)
• RNA, Long Noncoding (genetics)
• Liver Neoplasms (genetics, therapy)
• Prognosis
• Immunotherapy
• DNA Damage