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Zenghua Deng,1,2,* Kanghua Huang,3,* Dongfang Liu,1 Nan Luo,1,2 Tingting Liu,1 Long Han,1 Dexiao Du,1 Dongbo Lian,1,2 Zhaohui Zhong,4 Jirun Peng1,2 1Department of Surgery, Beijing Shijitan Hospital, Capital Medical University, Beijing, 100038, Peopleâs Republic of China; 2Ninth School of Clinical Medicine, Peking University, Beijing, 100038, Peopleâs Republic of China; 3Department of Radiation Oncology, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310009, Peopleâs Republic of China; 4Department of General Surgery, Peking University Peopleâs Hospital, Beijing, 100044, Peopleâs Republic of China*These authors contributed equally to this workCorrespondence: Jirun Peng; Zhaohui Zhong Email pengjr@medmail.com.cn; pengjr@bjsjth.cn; zhongzhaohui@pkuph.edu.cnBackground: Hepatocellular carcinoma (HCC) is the most common subtype of primary liver cancer, which causes â¼ 800,000 deaths annually world-wide. Immune checkpoint inhibitor (ICI) has reformed cancer therapy and achieved unprecedented results in various malignancies, including HCC. However, the response rate of immunotherapy is very low in HCC. Considereing the complicated and unique immune status in liver, we hypothesize that critical molecules will affect prognosis and correlate with immune context in the tumor microenvironment of HCC.Methods: Using KaplanâMeier plotter, GEPIA2 and Integrative Molecular Database of Hepatocellular Carcinoma (HCCDB), survival genes and their prognostic value were estimated in HCC. Based on Tumor Immune Estimation Resource (TIMER), association between survival genes and immune infiltration was examined in HCC. FunRich and STRING were used to analyze gene ontology and proteinâprotein interaction (PPI) Network, qRT-PCR was used to measure mRNA level of candidates; and a Cell Counting Kit-8 was used to measure proliferation of HCC cell line.Results: Using multiple databases, we identified 36 key prognostic genes highly expressed in HCC and associated with poor survival of patients. Meanwhile, the 36 gene signatures correlated with immune infiltration in HCC. Moreover, these genes were significantly associated with exhausted T cells and polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs) in HCC. Among the 36 key genes, SKA3, SGOL2, SPINDOC, TEDC2, TMCO3 and NUP205 were highly expressed in tumor samples compared with adjacent normal tissues in our HCC cohort (n=22). Additionally, proliferation of SMMC7721 cell line was inhibited when it interfered with SiRNA of each gene.Conclusion: The 36 genes may serve as potential prognostic biomarkers and molecular targets to ameliorate tumor immune microenvironment (TIME) in HCC and therefore represent a novel avenue for individualized immunotherapy in HCC.Keywords: HCC, prognosis, immune infiltrates, exhausted T cell, MDSC |
