Lv Lei, Wei Qinqin, Wang Zhiwen, Zhao Yujia, Chen Ni, Yi Qiyi
Anhui Cancer Hospital, West Branch of the First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China.
School of Basic Medical Sciences, Anhui Medical University, Hefei, China.
Front Bioeng Biotechnol. 2021 Jul 9;9:690186. doi: 10.3389/fbioe.2021.690186. eCollection 2021.
NLRC5 is an important regulator in antigen presentation and inflammation, and its dysregulation promotes tumor progression. In melanoma, the impact of NLRC5 expression on molecular phenotype, clinical characteristics, and tumor features is largely unknown. In the present study, public datasets from the Cancer Cell Line Encyclopedia (CCLE), Gene Expression Omnibus (GEO), The Cancer Genome Atlas (TCGA), and cBioPortal were used to address these issues. We identify that NLRC5 is expressed in both immune cells and melanoma cells in melanoma samples and its expression is regulated by SPI1 and DNA methylation. NLRC5 expression is closely associated with Breslow thickness, Clark level, recurrence, pathologic T stage, and ulceration status in melanoma. Truncating/splice mutations rather than missense mutations in NLRC5 could compromise the expression of downstream genes. Low expression of NLRC5 is associated with poor prognosis, low activity of immune-related signatures, low infiltrating level of immune cells, and low cytotoxic score in melanoma. Additionally, NLRC5 expression correlates with immunotherapy efficacy in melanoma. In summary, these findings suggest that NLRC5 acts as a tumor suppressor in melanoma via modulating the tumor immune microenvironment. Targeting the NLRC5 related pathway might improve efficacy of immunotherapy for melanoma patients.
NLRC5是抗原呈递和炎症反应中的重要调节因子，其失调会促进肿瘤进展。在黑色素瘤中，NLRC5表达对分子表型、临床特征和肿瘤特性的影响在很大程度上尚不清楚。在本研究中，我们使用了来自癌症细胞系百科全书（CCLE）、基因表达综合数据库（GEO）、癌症基因组图谱（TCGA）和cBioPortal的公共数据集来解决这些问题。我们发现，在黑色素瘤样本中，NLRC5在免疫细胞和黑色素瘤细胞中均有表达，且其表达受SPI1和DNA甲基化调控。NLRC5表达与黑色素瘤的Breslow厚度、Clark分级、复发、病理T分期和溃疡状态密切相关。NLRC5中的截断/剪接突变而非错义突变可能会损害下游基因的表达。NLRC5低表达与黑色素瘤患者的预后不良、免疫相关特征活性低、免疫细胞浸润水平低和细胞毒性评分低有关。此外，NLRC5表达与黑色素瘤的免疫治疗疗效相关。总之，这些发现表明，NLRC5通过调节肿瘤免疫微环境在黑色素瘤中发挥肿瘤抑制作用。靶向NLRC5相关通路可能会提高黑色素瘤患者免疫治疗的疗效。
