BMC Genomics (Feb 2024)

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

  • Fei Huang,
  • Chunyan Zhang,
  • Wenjing Yang,
  • Yan Zhou,
  • Yihui Yang,
  • Xinrong Yang,
  • Wei Guo,
  • Beili Wang

DOI
https://doi.org/10.1186/s12864-024-10055-1
Journal volume & issue
Vol. 25, no. 1
pp. 1 – 10

Abstract

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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.

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