Ding Jian, Meng Yan, Han Zelong, Luo Xiaobei, Guo Xuxue, Li Yiwen, Liu Side, Zhuang Kangmin
Guangdong Provincial Key Laboratory of Gastroenterology, Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, China.
Pazhou Lab, Guangzhou, China.
Front Oncol. 2022 May 16;12:811567. doi: 10.3389/fonc.2022.811567. eCollection 2022.
Despite emerging publications have elucidated a functional association between and tumors, no evidence about a pan-cancer analysis of is available. Our study first conducted a comprehensive assessment of its expression profiles, prognosis value, immune infiltration, and relevant cellular pathways bioinformatics techniques based on the public database of TCGA (The Cancer Genome Atlas). is highly expressed in most tumors, and it is associated with poor prognosis. Kaplan-Meier analysis and Cox regression analysis suggested that the high expression of was associated with poor overall survival (OS) in pan-cancer, Cox regression analysis also indicated high expression was correlated with disease-specific survival (DSS) and progression-free interval (PFI) in most tumors. We observed a regulation function of at genetic and epigenetic levels through CNA and DNA methylation using cBioPortal database. Based on Gene Set Enrichment Analysis, we first identified related pathways of and its potential biological functions in pan-cancer, was implicated in oncogenic pathways, and was related to extracellular matrix and immune regulation. We found that positively correlated with the levels of infiltrating cells such as TAMs and CAFs, but negatively correlated with CD8 T-cells by analyzing immune cell infiltration data we downloaded from published work and online databases, further investigation of the correlation between immunosuppressive genes, chemokines, chemokines receptors, and high expression showed a significant positive association in the vast majority of TCGA cancer types. These results indicated its role as an immune regulatory in cancers and suggested that RCN3 is a potential biomarker for immunotherapy. Also, we found that expression of RCN3 was much higher in CRC tissues than in normal tissues with a higher expression level of RCN3 closely correlating to advanced American Joint Committee on Cancer (AJCC) stage, poor differentiation, increased tumor size, and poor prognosis of CRC. Biological function experiments showed that RCN3 regulated CRC cells' proliferation and metastasis ability. Upregulation of RCN3 in CRC cells increased the expression of immune related factor, including TGFβ1, IL-10, and IL-6. Thus, our pan-cancer analysis offers a deep understanding of potential oncogenic roles of in different cancers.
尽管已有研究阐明了[具体内容]与肿瘤之间的功能关联,但尚无关于[具体内容]的泛癌分析证据。我们的研究首次基于TCGA(癌症基因组图谱)公共数据库,运用生物信息学技术对其表达谱、预后价值、免疫浸润及相关细胞通路进行了全面评估。[具体内容]在大多数肿瘤中高表达,且与不良预后相关。Kaplan-Meier分析和Cox回归分析表明,[具体内容]的高表达与泛癌中的总生存期(OS)较差相关,Cox回归分析还表明,在大多数肿瘤中,[具体内容]的高表达与疾病特异性生存期(DSS)和无进展生存期(PFI)相关。我们使用cBioPortal数据库通过CNA和DNA甲基化观察到[具体内容]在基因和表观遗传水平上的调控功能。基于基因集富集分析,我们首先确定了[具体内容]在泛癌中的相关通路及其潜在生物学功能,[具体内容]与致癌通路有关,且与细胞外基质和免疫调节相关。通过分析我们从已发表研究和在线数据库下载的免疫细胞浸润数据,我们发现[具体内容]与TAM和CAF等浸润细胞水平呈正相关,但与CD8 T细胞呈负相关,对免疫抑制基因、趋化因子、趋化因子受体与[具体内容]高表达之间的相关性进一步研究表明,在绝大多数TCGA癌症类型中存在显著正相关。这些结果表明了其在癌症中作为免疫调节因子的作用,并提示RCN3是免疫治疗的潜在生物标志物。此外,我们发现RCN3在结直肠癌组织中的表达远高于正常组织,RCN3的高表达水平与美国癌症联合委员会(AJCC)晚期、低分化、肿瘤大小增加以及结直肠癌的不良预后密切相关。生物学功能实验表明,RCN3调节结直肠癌细胞的增殖和转移能力。结直肠癌细胞中RCN3的上调增加了免疫相关因子的表达,包括TGFβ1、IL-10和IL-6。因此,我们的泛癌分析为深入了解[具体内容]在不同癌症中的潜在致癌作用提供了依据。