Fang Yuan, Tang Weiqiang, Zhao Dan, Zhang Xiaoli, Li Na, Yang Yang, Jin Li, Li Zhitao, Wei Benkai, Miao Yinglei, Zeng Zhong, Huang Hanfei
Organ Transplantation Center, the First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, China.
Institute of Clinical Medicine, The First Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang, Hunan, China.
Cancer Biomark. 2023;38(2):225-239. doi: 10.3233/CBM-230073.
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.
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.
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.
The study findings demonstrate that HELLS is an important factor in promoting LIHC malignancy and might serve as a potential biomarker for LIHC.
淋巴特异性解旋酶（HELLS）是一种SNF2样染色质重塑酶，通过其DNA甲基化功能在肿瘤进展中起关键作用。然而，HELLS对肝细胞癌（LIHC）免疫浸润和预后的影响仍不确定。
利用肿瘤免疫评估资源（TIMER）数据库探索HELLS的泛癌mRNA表达及其与免疫的相关性。使用GEPIA2验证HELLS表达与生存之间的相关性。通过基因集富集分析（基因本体论和京都基因与基因组百科全书）以及构建基因-基因和蛋白质-蛋白质相互作用网络（PPI）来探索HELLS在癌症中的作用。此外，还在LIHC中探索了DNA甲基化、HELLS表达和免疫相关基因之间的相关性。使用qRT-PCR和蛋白质印迹法测定LIHC临床样本中的HELLS表达。通过体外转染实验探索下调HELLS表达对肝癌细胞的影响。
在几种癌症中发现了高HELLS mRNA表达，并且与LIHC的较差预后显著相关。此外，HELLS表达与LIHC中的肿瘤浸润淋巴细胞和免疫检查点基因呈正相关。生物信息学分析表明，HELLS的DNA甲基化可能与免疫反应有关。来自TCGA-LIHC数据集、临床样本和功能分析的结果表明，HELLS促进了LIHC的肿瘤进展。
研究结果表明，HELLS是促进LIHC恶性肿瘤的重要因素，可能作为LIHC的潜在生物标志物。
