Zhou Zixuan, Ma Zuyi, Li Zhenchong, Zhuang Hongkai, Liu Chunsheng, Gong Yuanfeng, Huang Shanzhou, Zhang Chuanzhao, Hou Baohua
South China University of Technology School of Medicine, Guangzhou 510006,Guangdong Province, China.
Department of General Surgery, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou 510080, China.
J Cancer. 2021 Aug 3;12(19):5797-5806. doi: 10.7150/jca.57082. eCollection 2021.
Recent evidence has shown that CKLF-like MARVEL transmembrane domain containing 3 (CMTM3) promoted carcinogenesis and tumor progression in a variety of cancer types. The goal of our study is to investigate the association between CMTM3 and pancreatic cancer (PC). In current study, data from public databases was used to analyze CMTM3 expression in PC. Quantitative real-time polymerase chain reaction (qRT-PCR) and immunohistochemistry (IHC) were used to investigate CMTM3 expression and determine its clinical significance in PC. Then CMTM3 promoting PC aggressiveness was demonstrated experiments by cell proliferation and migration assay. Functional and pathway enrichment analyses were performed to evaluate the potential role of CMTM3 in PC. Results of qRT-PCR and IHC revealed that CMTM3 was significantly overexpressed in PC tissues. High CMTM3 expression was an independent risk factor for poor prognosis of PC patients. Overexpression of CMTM3 was associated with poor overall survival (P-value =0.031) and disease-free survival (P-value =0.0047) in the TCGA cohort. Functional and pathway enrichment analyses showed that CMTM3 were enriched in "Regulation of cell proliferation and regulation of cell differentiation, cell morphogenesis, regulation of cell differentiation, Hedgehog signaling pathway, Wnt signaling pathway, ECM-receptor interaction and pathways in cancer". In PC cell lines, CCK8, clone formation and transwell assays showed that CMTM3 knockdown inhibited cells proliferation and migration. CMTM3 was overexpressed and promotes tumor aggressiveness in PC. Our findings provided a novel therapeutic target for PC.
近期证据表明，含CKLF样MARVEL跨膜结构域3（CMTM3）在多种癌症类型中促进了肿瘤发生和肿瘤进展。我们研究的目的是探讨CMTM3与胰腺癌（PC）之间的关联。在当前研究中，使用来自公共数据库的数据来分析PC中CMTM3的表达。采用定量实时聚合酶链反应（qRT-PCR）和免疫组织化学（IHC）来研究CMTM3的表达并确定其在PC中的临床意义。然后通过细胞增殖和迁移实验证明CMTM3促进PC的侵袭性。进行功能和通路富集分析以评估CMTM3在PC中的潜在作用。qRT-PCR和IHC结果显示，CMTM3在PC组织中显著过表达。CMTM3高表达是PC患者预后不良 的独立危险因素。在TCGA队列中，CMTM3过表达与总生存期差（P值=0.031）和无病生存期差（P值=0.0047）相关。功能和通路富集分析表明，CMTM3富集于“细胞增殖调控、细胞分化调控、细胞形态发生、细胞分化调控、Hedgehog信号通路、Wnt信号通路、ECM-受体相互作用和癌症中的通路”。在PC细胞系中，CCK8、克隆形成和transwell实验表明，CMTM3敲低抑制细胞增殖和迁移。CMTM3在PC中过表达并促进肿瘤侵袭性。我们的研究结果为PC提供了一个新的治疗靶点。
