CD48 suppresses proliferation and migration as an immune-related prognostic signature in the cervical cancer immune microenvironment.

IF 3.3 3区 医学 Q2 ONCOLOGY
Yue Ma, Zhuo Yang, Jing Liu, Danbo Wang
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引用次数: 0

Abstract

Cervical cancer (CC) is one of the most common malignant tumors in gynecology. Immunotherapy and targeted therapy are two particularly effective treatments. In this study, weighted gene co-expression network analysis and CIBERSORT algorithm that quantifies the composition of immune cells were used to analyze CC expression data based on the GEO database and identify modules related to T cells. Five candidate hub genes were identified by tumor-infiltrating immune cells estimation and Kaplan-Meier survival analysis according to CC data from The Cancer Genome Atlas (TCGA). Chemotherapeutic response, methylation, and gene mutation analyses were implemented so that the five candidate hub genes identified may be the potential biomarkers and therapeutic targets which were related to T cell infiltration. Moreover, the results of RT-qPCR revealed that CD48 was a tumor suppressor gene, which was negatively correlated with CC stages, lymph node metastasis, and differentiation. Furthermore, the functional study verified that the interference of CD48 was able to boost the proliferation and migration ability in vitro and the growth of transplanted tumors in vivo. Overall, we identified molecular targets related to immune infiltration and prognosis, regarded CD48 as a key molecule involved in the progression of CC, thus providing new insights into the development of molecular therapy and immunotherapeutics against CC.

CD48 可抑制增殖和迁移,是宫颈癌免疫微环境中与免疫相关的预后特征。
宫颈癌(CC)是妇科最常见的恶性肿瘤之一。免疫疗法和靶向疗法是两种特别有效的治疗方法。本研究利用加权基因共表达网络分析和量化免疫细胞组成的CIBERSORT算法,分析了基于GEO数据库的CC表达数据,并确定了与T细胞相关的模块。根据癌症基因组图谱(The Cancer Genome Atlas,TCGA)的CC数据,通过对肿瘤浸润免疫细胞的估计和Kaplan-Meier生存分析,确定了五个候选中心基因。通过化疗反应、甲基化和基因突变分析,确定了五个候选中枢基因可能是与T细胞浸润相关的潜在生物标志物和治疗靶点。此外,RT-qPCR结果显示,CD48是一个抑癌基因,与CC分期、淋巴结转移和分化呈负相关。此外,功能研究还验证了干扰 CD48 能够促进体外肿瘤的增殖和迁移能力以及体内移植肿瘤的生长。总之,我们发现了与免疫浸润和预后相关的分子靶点,认为CD48是参与CC进展的关键分子,从而为开发针对CC的分子疗法和免疫疗法提供了新的见解。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Carcinogenesis
Carcinogenesis 医学-肿瘤学
CiteScore
9.20
自引率
2.10%
发文量
95
审稿时长
1 months
期刊介绍: Carcinogenesis: Integrative Cancer Research is a multi-disciplinary journal that brings together all the varied aspects of research that will ultimately lead to the prevention of cancer in man. The journal publishes papers that warrant prompt publication in the areas of Biology, Genetics and Epigenetics (including the processes of promotion, progression, signal transduction, apoptosis, genomic instability, growth factors, cell and molecular biology, mutation, DNA repair, genetics, etc.), Cancer Biomarkers and Molecular Epidemiology (including genetic predisposition to cancer, and epidemiology), Inflammation, Microenvironment and Prevention (including molecular dosimetry, chemoprevention, nutrition and cancer, etc.), and Carcinogenesis (including oncogenes and tumor suppressor genes in carcinogenesis, therapy resistance of solid tumors, cancer mouse models, apoptosis and senescence, novel therapeutic targets and cancer drugs).
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