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Article

A Multi-Omics Analysis of NASH-Related Prognostic Biomarkers Associated with Drug Sensitivity and Immune Infiltration in Hepatocellular Carcinoma

by
Yongting Liu
1,
Zhaohui Jiang
1,
Xin Zhou
1,
Yin Li
1,
Ping Liu
1,
Yihong Chen
1,
Jun Tan
2,
Changjing Cai
1,
Ying Han
1,
Shan Zeng
1,
Hong Shen
1,3,* and
Ziyang Feng
1,*
1
Department of Oncology, Xiangya Hospital, Central South University, Changsha 410008, China
2
Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha 410008, China
3
National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha 410008, China
*
Authors to whom correspondence should be addressed.
J. Clin. Med. 2023, 12(4), 1286; https://doi.org/10.3390/jcm12041286
Submission received: 19 December 2022 / Revised: 1 February 2023 / Accepted: 3 February 2023 / Published: 6 February 2023
(This article belongs to the Topic Diagnosis, Management, and Prognostic Assessment of Chronic Disease)
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Abstract

Background: Nonalcoholic steatohepatitis (NASH)-driven hepatocellular carcinoma (HCC) is becoming a major health-related problem. The exploration of NASH-related prognostic biomarkers and therapeutic targets is necessary. Methods: Data were downloaded from the GEO database. The “glmnet” package was used to identify differentially expressed genes (DEGs). The prognostic model was constructed by the univariate Cox and LASSO regression analyses. Validation of the expression and prognosis by immunohistochemistry (IHC) in vitro. Drug sensitivity and immune cell infiltration were analyzed by CTR-DB and ImmuCellAI. Results: We constructed a prognostic model that identified the NASH-related gene set (DLAT, IDH3B, and MAP3K4), which was validated in a real-world cohort. Next, seven prognostic transcription factors (TFs) were identified. The prognostic ceRNA network included three mRNAs, four miRNAs, and seven lncRNAs. Finally, we found that the gene set was associated with drug response which was validated in six clinical trial cohorts. Moreover, the expression level of the gene set was inversely correlated with CD8 T cell infiltration in HCC. Conclusions: We established a NASH-related prognostic model. Upstream transcriptome analysis and the ceRNA network provided clues for mechanism exploration. The mutant profile, drug sensitivity, and immune infiltration analysis further guided precise diagnosis and treatment strategies.
Keywords: multi-omics analysis; NASH-driven HCC; prognostic biomarkers; drug sensitivity; immune infiltration multi-omics analysis; NASH-driven HCC; prognostic biomarkers; drug sensitivity; immune infiltration

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MDPI and ACS Style

Liu, Y.; Jiang, Z.; Zhou, X.; Li, Y.; Liu, P.; Chen, Y.; Tan, J.; Cai, C.; Han, Y.; Zeng, S.; et al. A Multi-Omics Analysis of NASH-Related Prognostic Biomarkers Associated with Drug Sensitivity and Immune Infiltration in Hepatocellular Carcinoma. J. Clin. Med. 2023, 12, 1286. https://doi.org/10.3390/jcm12041286

AMA Style

Liu Y, Jiang Z, Zhou X, Li Y, Liu P, Chen Y, Tan J, Cai C, Han Y, Zeng S, et al. A Multi-Omics Analysis of NASH-Related Prognostic Biomarkers Associated with Drug Sensitivity and Immune Infiltration in Hepatocellular Carcinoma. Journal of Clinical Medicine. 2023; 12(4):1286. https://doi.org/10.3390/jcm12041286

Chicago/Turabian Style

Liu, Yongting, Zhaohui Jiang, Xin Zhou, Yin Li, Ping Liu, Yihong Chen, Jun Tan, Changjing Cai, Ying Han, Shan Zeng, and et al. 2023. "A Multi-Omics Analysis of NASH-Related Prognostic Biomarkers Associated with Drug Sensitivity and Immune Infiltration in Hepatocellular Carcinoma" Journal of Clinical Medicine 12, no. 4: 1286. https://doi.org/10.3390/jcm12041286

APA Style

Liu, Y., Jiang, Z., Zhou, X., Li, Y., Liu, P., Chen, Y., Tan, J., Cai, C., Han, Y., Zeng, S., Shen, H., & Feng, Z. (2023). A Multi-Omics Analysis of NASH-Related Prognostic Biomarkers Associated with Drug Sensitivity and Immune Infiltration in Hepatocellular Carcinoma. Journal of Clinical Medicine, 12(4), 1286. https://doi.org/10.3390/jcm12041286

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