CBX3 Promotes Gastric Cancer Progression and Affects Factors Related to Immunotherapeutic Responses.
CBX3 Promotes Gastric Cancer Progression and Affects Factors Related to Immunotherapeutic Responses.
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CBX3 促进胃癌进展并影响与免疫治疗反应相关的因素
DOI：
10.2147/cmar.s271807
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发表时间：
2020
影响因子：
3.3
通讯作者：
You J
中科院分区：
文献类型：
--
作者：
Lin H;Lian J;Xia L;Guan G;You J
Chromobox 3 (CBX3) 是 chromobox 家族蛋白的一员，在肿瘤进展中发挥着关键作用，但 CBX3 在胃癌中的确切功能仍不清楚。目前的研究主要探讨CBX3在胃癌中的作用机制及临床价值。对来自癌症基因组图谱 (TCGA) 和基因表达综合 (GEO) 的基因表达队列进行分析，以评估 CBX3 在胃癌中的作用。通过免疫组织化学 (IHC) 进一步测定 CBX3 表达。分别通过集落形成、细胞周期和跨孔实验探讨了 CBX3 对增殖、迁移和细胞周期的功能。此外，利用AGS细胞和两个队列中的RNA测序（RNA-seq）来探索CBX3的具体机制。 CBX3在人胃癌组织中表达上调，且表达水平与不良体征密切相关。胃癌细胞中CBX3的敲低可显着抑制恶性表型。此外，RNA-seq分析显示CBX3调节与细胞周期、错配修复和免疫相关途径相关的基因。此外，CBX3的表达与肿瘤浸润淋巴细胞（TIL）的丰度、PDCD1和PDCD1LG2的表达以及免疫治疗反应呈显着负相关。此外，CBX3影响化疗的有效性，从而影响胃癌患者的预后。 CBX3 有助于胃癌进展，并与化疗和免疫治疗反应相关。 CBX3可能作为一种新的诊断生物标志物以及胃癌免疫治疗和化疗的潜在靶点。
Chromobox 3 (CBX3) is a member of the chromobox family proteins, which plays a critical role in tumor progression, but the exact function of CBX3 in gastric cancer remains unknown. The current research mainly investigates the underlying mechanisms and clinical value of CBX3 in gastric cancer. Gene expression cohorts from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) were analyzed to assess the effect of CBX3 in gastric cancer. CBX3 expression was further determined by immunohistochemistry (IHC). The function of CBX3 on proliferation, migration and the cell cycle was explored via colony-forming, cell cycle and transwell assays, respectively. Moreover, RNA sequencing (RNA-seq) in AGS cells and two cohorts was utilized to explore the specific mechanism of CBX3. CBX3 expression was upregulated in human gastric cancer tissues and the expression level was closely associated with adverse signs. Knockdown of CBX3 in gastric cancer cells significantly inhibited the malignant phenotype. In addition, RNA-seq analysis revealed that CBX3 regulates genes related to the cell cycle, mismatch repair and immune-related pathways. Furthermore, the expression of CBX3 was significantly and inversely related to the abundance of tumor-infiltrating lymphocytes (TILs), PDCD1 and PDCD1LG2 expression and immunotherapy responses. Moreover, CBX3 influences the effectiveness of chemotherapy, thereby impacting the prognosis of gastric cancer patients. CBX3 contributes to gastric cancer progression and is associated with chemotherapy and immunotherapy response. CBX3 may serve as a new diagnostic biomarker and potential target for immunotherapy and chemotherapy in gastric cancer.