AUTHOR=Shi Yanlong , Huang Guo , Jiang Fei , Zhu Jun , Xu Qiyang , Fang Hanlu , Lan Sheng , Pan Ziyuan , Jian Haokun , Li Li , Zhang Yewei TITLE=Deciphering a mitochondria-related signature to supervise prognosis and immunotherapy in hepatocellular carcinoma JOURNAL=Frontiers in Immunology VOLUME=13 YEAR=2022 URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2022.1070593 DOI=10.3389/fimmu.2022.1070593 ISSN=1664-3224 ABSTRACT=Background

Hepatocellular carcinoma (HCC) is a major public health problem in humans. The imbalance of mitochondrial function has been discovered to be closely related to the development of cancer recently. However, the role of mitochondrial-related genes in HCC remains unclear.

Methods

The RNA-sequencing profiles and patient information of 365 samples were derived from the Cancer Genome Atlas (TCGA) dataset. The mitochondria-related prognostic model was established by univariate Cox regression analysis and LASSO Cox regression analysis. We further determined the differences in immunity and drug sensitivity between low- and high-risk groups. Validation data were obtained from the International Cancer Genome Consortium (ICGC) dataset of patients with HCC. The protein and mRNA expression of six mitochondria-related genes in tissues and cell lines was verified by immunohistochemistry and qRT-PCR.

Results

The six mitochondria-related gene signature was constructed for better prognosis forecasting and immunity, based on which patients were divided into high-risk and low-risk groups. The ROC curve, nomogram, and calibration curve exhibited admirable clinical predictive performance of the model. The risk score was associated with clinicopathological characteristics and proved to be an independent prognostic factor in patients with HCC. The above results were verified in the ICGC validation cohort. Compared with normal tissues and cell lines, the protein and mRNA expression of six mitochondria-related genes was upregulated in HCC tissues and cell lines.

Conclusion

The signature could be an independent factor that supervises the immunotherapy response of HCC patients and possess vital guidance value for clinical diagnosis and treatment.