Identifying tumor immunity-associated molecular features in liver hepatocellular carcinoma by multi-omics analysis

Qianyun Shen; Yin He; Jiajie Qian; Xiaosheng Wang

doi:10.3389/fmolb.2022.960457

Identifying tumor immunity-associated molecular features in liver hepatocellular carcinoma by multi-omics analysis

Front Mol Biosci. 2022 Oct 20:9:960457. doi: 10.3389/fmolb.2022.960457. eCollection 2022.

Authors

Qianyun Shen¹, Yin He^{2

3

4}, Jiajie Qian¹, Xiaosheng Wang^{2

3

4}

Affiliations

¹ Department of Gastrointestinal Surgery, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China.
² Biomedical Informatics Research Lab, School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing, China.
³ Cancer Genomics Research Center, School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing, China.
⁴ Big Data Research Institute, China Pharmaceutical University, Nanjing, China.

Abstract

Background: Although current immunotherapies have achieved some successes for hepatocellular carcinoma (HCC) patients, their benefits are limited for most HCC patients. Therefore, the identification of biomarkers for promoting immunotherapeutic responses in HCC is urgently needed. Methods: Using the TCGA HCC cohort, we investigated correlations of various molecular features with antitumor immune signatures (CD8⁺ T cell infiltration and cytolytic activity) and an immunosuppressive signature (PD-L1 expression) in HCC. These molecular features included mRNAs, microRNAs (miRNAs), long non-coding RNAs (lncRNAs), proteins, and pathways. Results: We found that the mutations of several oncogenes and tumor suppressor genes significantly correlated with reduced antitumor immune signatures, including TTN, CTNNB1, RB1, ZFHX4, and TP53. It indicates that these genes' mutations may inhibit antitumor immune responses in HCC. Four proteins (Syk, Lck, STAT5, and Caspase-7) had significant positive expression correlations with CD8⁺ T cell enrichment, cytolytic activity, and PD-L1 expression in HCC. It suggests that these proteins' expression could be useful biomarkers for the response to immune checkpoint inhibitors Similiarly, we identified other types of biomarkers potentially useful for predicting the response to ICIs, including miRNAs (hsa-miR-511-5p, 150-3p, 342-3p, 181a-3p, 625-5p, 4772-3p, 155-3p, 142-5p, 142-3p, 155-5p, 625-3p, 1976, 7702), many lncRNAs, and pathways (apoptosis, cytokine-cytokine receptor interaction, Jak-STAT signaling, MAPK signaling, PI3K-AKT signaling, HIF-1 signaling, ECM receptor interaction, focal adhesion, and estrogen signaling). Further, tumor mutation burden showed no significant correlation with antitumor immunity, while tumor aneuploidy levels showed a significant negative correlation with antitumor immunity. Conclusion: The molecular features significantly associated with HCC immunity could be predictive biomarkers for immunotherapeutic responses in HCC patients. They could also be potential intervention targets for boosting antitumor immunity and immunotherapeutic responses in HCC.

Keywords: antitumor immunity; biomarker; cancer immunotherapy; hepatocellular carcinoma; multi-omics analysis.