A novel myeloid cell marker genes related signature can indicate immune infiltration and predict prognosis of hepatocellular carcinoma: Integrated analysis of bulk and single-cell RNA sequencing

Su-Su Zheng; Yan-Fang Wu; Bo-Heng Zhang; Cheng Huang; Tong-Chun Xue

doi:10.3389/fmolb.2023.1118377

A novel myeloid cell marker genes related signature can indicate immune infiltration and predict prognosis of hepatocellular carcinoma: Integrated analysis of bulk and single-cell RNA sequencing

Front Mol Biosci. 2023 Mar 7:10:1118377. doi: 10.3389/fmolb.2023.1118377. eCollection 2023.

Authors

Su-Su Zheng¹, Yan-Fang Wu¹, Bo-Heng Zhang^{1

2

3}, Cheng Huang⁴, Tong-Chun Xue²

Affiliations

¹ Department of Hepatic Oncology, Xiamen Clinical Research Center for Cancer Therapy, Zhongshan Hospital, Fudan University (Xiamen Branch), Xiamen, China.
² The Liver Cancer Institute, Zhongshan Hospital and Shanghai Medical School, Fudan University, Key Laboratory for Carcinogenesis and Cancer Invasion, The Chinese Ministry of Education, Shanghai, China.
³ Center for Evidence-based Medicine, Shanghai Medical School, Fudan University, Shanghai, China.
⁴ Department of Liver Surgery, Liver Cancer Institute, Zhongshan Hospital, and Key Laboratory of Carcinogenesis and Cancer Invasion (Ministry of Education), Fudan University, Shanghai, China.

Abstract

Myeloid cells are physiologically related to innate immunity and inflammation. Tumor-associated myeloid cells gained increasing interest because of their critical roles in tumor progression and anticancer immune responses in human malignancies. However, the associations between tumor-associated myeloid cell-related genes and hepatocellular carcinoma have yet to be revealed. Here, through the integrating analysis of bulk and single-cell RNA (scRNA) sequencing of public HCC samples, we developed a gene signature to investigate the role of HCC-specific myeloid signature genes in HCC patients. We firstly defined 317 myeloid cell marker genes through analyzing scRNA data of HCC from the GEO dataset. After selecting the differentially expressed genes, eleven genes were also proved prognostic. Then we built a gene signature from the TCGA cohort and verified further with the ICGC dataset by applying the LASSO Cox method. An eight genes signature (FABP5, C15orf48, PABPC1, TUBA1B, AKR1C3, NQO1, AKR1B10, SPP1) was achieved finally. Patients in the high risk group correlated with higher tumor stages and poor survival than those in the low-risk group. The risk score was proved to be an independent risk factor for prognosis. The high risk group had higher infiltrations of dendritic cells, macrophages and Tregs. And the APC co-inhibition, T cell co-inhibition pathways were also activated. Besides, the risk score positively correlated with multidrug resistance proteins. In conclusion, our myeloid cell marker genes related signature can predict patients' survival and may also indicate the levels of immune infiltration and drug resistance.

Keywords: drug resistance; hepatocellular carcinoma; immune infiltration; prognosis; single-cell RNA sequencing; tumor associated myeloid cells.

Grants and funding

This research was supported by grants from the Medical and Health Project of Xiamen City (Key Project, No. 3502Z20191105); Natural Science Foundation of Fujian Province (grant number 2022J05332); Foundation of Xiamen Branch, Zhongshan Hospital, Fudan University of China (2020ZSXMYS01); Science and Technology Bureau of Xiamen City (3502Z20224ZD1081); Foundation of Zhongshan Hospital, Fudan University of China (2020ZSLC60).