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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.

SUBMITTER: Huang F 

PROVIDER: S-EPMC10851502 | biostudies-literature | 2024 Feb

REPOSITORIES: biostudies-literature

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Publications

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

Huang Fei F   Zhang Chunyan C   Yang Wenjing W   Zhou Yan Y   Yang Yihui Y   Yang Xinrong X   Guo Wei W   Wang Beili B  

BMC genomics 20240208 1


<h4>Background</h4>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.<h4>Methods</h4>Data of HCC samples were obtained from the Cancer Genome Atlas (TCGA), and a list of DDR-related genes was extracted from the Molecular Si  ...[more]

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