INHBB 是结直肠癌中与癌症促进途径相关的新型预后生物标志物。
INHBB Is a Novel Prognostic Biomarker Associated with Cancer-Promoting Pathways in Colorectal Cancer.
机构信息
Department of Gastrointestinal Surgery, The First Affiliated Hospital of Shantou University Medical College, Shantou, 515041 Guangdong, China.
Shantou University Medical College, China.
出版信息
Biomed Res Int. 2020 Oct 6;2020:6909672. doi: 10.1155/2020/6909672. eCollection 2020.
BACKGROUND
Inhibin subunit beta B (INHBB) is a protein-coding gene that participated in the synthesis of the transforming growth factor- (TGF-) family members. The study is aimed at exploring the clinical significance of INHBB in patients with colorectal cancer (CRC) by bioinformatics analysis.
METHODS
Real-time PCR and analyses of Oncomine, Gene Expression Omnibus (GEO), and The Cancer Genome Atlas (TCGA) databases were utilized to evaluate the INHBB gene transcription level of colorectal cancer (CRC) tissue. We evaluated the INHBB methylation level and the relationship between expression and methylation levels of CpG islands in CRC tissue. The corresponding clinical data were obtained to further explore the association of INHBB with clinical and survival features. In addition, Gene Set Enrichment Analysis (GSEA) was performed to explore the gene ontology and signaling pathways of INHBB involved.
RESULTS
INHBB expression was elevated in CRC tissue. Although the promoter of INHBB was hypermethylated in CRC, methylation did not ultimately correlate with the expression of INHBB. Overexpression of INHBB was significantly and positively associated with invasion depth, distant metastasis, and TNM stage. Cox regression analyses and Kaplan-Meier survival analysis indicated that high expression of INHBB was correlated with worse overall survival (OS) and disease-free survival (DFS). GSEA showed that INHBB was closely correlated with 5 cancer-promoting signaling pathways including the Hedgehog signaling pathway, ECM receptor interaction, TGF- signaling pathway, focal adhesion, and pathway in cancer. INHBB expression significantly promoted macrophage infiltration and inhibited memory T cell, mast cell, and dendritic cell infiltration. INHBB expression was positively correlated with stromal and immune scores of CRC samples.
CONCLUSION
INHBB might be a potential prognostic biomarker and a novel therapeutic target for CRC.
背景
抑制素亚基β B（INHBB）是一种参与转化生长因子-（TGF-）家族成员合成的蛋白质编码基因。本研究旨在通过生物信息学分析探讨 INHBB 在结直肠癌（CRC）患者中的临床意义。
方法
利用实时 PCR 以及 Oncomine、基因表达综合数据库（GEO）和癌症基因组图谱（TCGA）数据库分析评估结直肠癌（CRC）组织中 INHBB 基因转录水平。评估 CRC 组织中 INHBB 甲基化水平及 CpG 岛表达与甲基化水平的关系。获取相应的临床资料，进一步探讨 INHBB 与临床和生存特征的关系。此外，还进行了基因集富集分析（GSEA），以探讨 INHBB 涉及的基因本体论和信号通路。
结果
INHBB 在 CRC 组织中表达上调。尽管 INHBB 的启动子在 CRC 中呈高甲基化，但甲基化最终并未与 INHBB 的表达相关。INHBB 的过表达与浸润深度、远处转移和 TNM 分期显著且呈正相关。Cox 回归分析和 Kaplan-Meier 生存分析表明，INHBB 的高表达与总生存期（OS）和无病生存期（DFS）较差相关。GSEA 显示，INHBB 与包括 Hedgehog 信号通路、ECM 受体相互作用、TGF-信号通路、焦点黏附以及癌症通路在内的 5 种促进癌症发生的信号通路密切相关。INHBB 表达显著促进巨噬细胞浸润，抑制记忆 T 细胞、肥大细胞和树突状细胞浸润。INHBB 表达与 CRC 样本的基质和免疫评分呈正相关。
结论
INHBB 可能是 CRC 的一个潜在预后生物标志物和新的治疗靶点。
Zotero 插件