Immunological function and prognostic value of lymphoid-specific helicase in liver hepatocellular carcinoma

Article type: Research Article

Authors: Fang, Yuan^{a; 1} | Tang, Weiqiang^{b; 1} | Zhao, Dan^{c; 1} | Zhang, Xiaoli^d | Li, Na^a | Yang, Yang^e | Jin, Li^a | Li, Zhitao^a | Wei, Benkai^a | Miao, Yinglei^{f; g} | Zeng, Zhong^{a; *} | Huang, Hanfei^{a; *}

Affiliations: [a] Organ Transplantation Center, the First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, China | [b] Institute of Clinical Medicine, The First Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang, Hunan, China | [c] Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China | [d] Gastrointestinal and Hernia Surgery, The First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, China | [e] Otorhinolaryngology Head and Neck Surgery, Baoshan People’s Hospital, Baoshang, Yunnan, China | [f] Department of Gastroenterology, The First Affiliated Hospital of Kunming Medical University, Yunnan, China | [g] Yunnan Province Clinical Research Center for Digestive Diseases, Yunnan, China

Correspondence: [*] Corresponding authors: Zhong Zeng and Han-Fei Huang, Organ Transplantation Center, The First Affiliated Hospital of Kunming Medical University, 295 Xichang Road, Kunming 650032, Yunnan, China. E-mails: zengzhong@kmmu.edu.cn; huanghanfei @kmmu.edu.cn.

Note: [1] These authors contributed equally to this work.

Abstract: BACKGROUND: Lymphoid-specific helicase (HELLS), a SNF2-like chromatin-remodeling enzyme, plays a key role in tumor progression via its DNA methylation function. However, the effects of HELLS on immune infiltration and prognosis in liver hepatocellular carcinoma (LIHC) remain uncertain. METHODS: The Tumor Immune Estimation Resource (TIMER) database was employed to explore the pan-cancer mRNA expression of HELLS and its correlation with immunity. GEPIA2 was used to verify the correlation between HELLS expression and survival. The role of HELLS in cancer was explored via gene set enrichment analysis (Gene Ontology and Kyoto Encyclopedia of Genes and Genomes) and the construction of gene-gene and protein-protein interaction networks (PPI). Additionally, correlations between DNA methylation, HELLS expression, and immune-related genes were explored in LIHC. HELLS expression in LIHC clinical samples was determined using qRT-PCR and western blotting. The effects of downregulated HELLS expression in hepatocellular carcinoma cells was explored via transfection experiments in vitro. RESULTS: High HELLS mRNA expression was identified in several cancers and was significantly associated with poorer prognosis in LIHC. Furthermore, HELLS expression was positively correlated with tumor-infiltrating lymphocytes and immune checkpoint genes in LIHC. Bioinformatics analysis suggested that DNA methylation of HELLS may be associated with the immune response. Results from the TCGA-LIHC dataset, clinical samples, and functional analysis indicated that HELLS contributed to tumor progression in LIHC. CONCLUSION: The study findings demonstrate that HELLS is an important factor in promoting LIHC malignancy and might serve as a potential biomarker for LIHC.

Keywords: HELLS, immune, tumor-infiltrating, prognosis, DNA methylation, liver hepatocellular carcinoma

DOI: 10.3233/CBM-230073

Journal: Cancer Biomarkers, vol. 38, no. 2, pp. 225-239, 2023