Zhang Zilong, Shang Jin, Dai Zonglin, Yao Yutong, Shi Ying, Zhong Deyuan, Liang Yuxin, Lai Chunyou, Yang Qinyan, Feng Tianhang, Huang Xiaolun
Department of Hepatobiliary-Pancreatic Surgery, Cell Transplantation Center, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, China.
Chinese Academy of Sciences Sichuan Translational Medicine Research Hospital, Chengdu, China.
Front Genet. 2022 May 5;13:848391. doi: 10.3389/fgene.2022.848391. eCollection 2022.
Pancreatic adenocarcinoma (PAAD) is among the most common types of cancer with a poor prognosis. Transmembrane protein 170B (TMEM170B) has been reported to suppress breast cancer proliferation, metastasis, and tumorigenesis and is related to prognosis. However, its role in PAAD and the underlying molecular mechanisms are yet to be investigated. We performed a comprehensive analysis of RNA sequencing data obtained from the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases to determine TMEM170B expression. Immunostaining and real-time polymerase chain reaction (RT-PCR) were done to determine TMEM170B expression in human pancreatic cancer cell lines and tissue specimens. Furthermore, the correlation of TMEM170B with clinicopathological features and PAAD prognosis was investigated, and the mechanisms were explored through enrichment analysis and immune cell infiltration analysis. TCGA and GEO dataset analysis revealed that TMEM170B expression in PAAD tissue samples was significantly lower than that in non-tumorous tissues, which was further confirmed by immunohistochemistry and RT-PCR. Low TMEM170B expression was associated with poor differentiation ( = 0.014). Multivariate analysis identified that TMEM170B is an independent indicator for overall survival [hazard ratio (HR) = 0.116, 95% confidence interval (CI) = 0.014-0.995; = 0.049] and disease-free survival (HR = 0.19, 95% CI = 0.04-0.910; = 0.038) in patients with PAAD. Additionally, TMEM170B was involved in immune-related gene sets, including those related to chemokine signaling pathways and innate and adaptive immunity. High TMEM170B expression was linked to antitumor immune microenvironment with a high infiltration of B cells, T cells, dendritic cells, monocytes, M1 macrophages, neutrophil, and natural killer cells and a low infiltration of Tregs and myeloid-derived suppressor cells (all < 0.05). There is an urgent need to identify clinical prognostic biomarkers and targeted drugs for pancreatic cancer treatment. In this study, the expression status and prognostic value of transmembrane protein 170B (TMEM170B) in pancreatic adenocarcinoma were elucidated. Furthermore, TMEM170B, as a tumor suppressor gene, induced antitumor immune effects, including increased tumor infiltration of immune effector cells and reduced levels of inhibitory immune molecules and regulatory cells. Therefore, TMEM170B could be regarded as a novel target in preventing the progression of pancreatic cancer. The findings suggest that low TMEM170B expression is remarkably correlated with poor PAAD prognosis, which might provide a therapeutic target for PAAD.
胰腺腺癌(PAAD)是预后较差的最常见癌症类型之一。据报道,跨膜蛋白170B(TMEM170B)可抑制乳腺癌的增殖、转移和肿瘤发生,且与预后相关。然而,其在PAAD中的作用及潜在分子机制尚待研究。我们对从基因表达综合数据库(GEO)和癌症基因组图谱(TCGA)数据库获得的RNA测序数据进行了全面分析,以确定TMEM170B的表达情况。通过免疫染色和实时聚合酶链反应(RT-PCR)来确定TMEM170B在人胰腺癌细胞系和组织标本中的表达。此外,研究了TMEM170B与临床病理特征及PAAD预后的相关性,并通过富集分析和免疫细胞浸润分析探索其机制。TCGA和GEO数据集分析显示,PAAD组织样本中TMEM170B的表达明显低于非肿瘤组织,免疫组织化学和RT-PCR进一步证实了这一点。TMEM170B低表达与低分化相关(P = 0.014)。多变量分析确定TMEM170B是PAAD患者总生存期[风险比(HR)= 0.116,95%置信区间(CI)= 0.014 - 0.995;P = 0.049]和无病生存期(HR = 0.19,95% CI = 0.04 - 0.910;P = 0.038)的独立指标。此外,TMEM170B参与了免疫相关基因集,包括那些与趋化因子信号通路以及固有免疫和适应性免疫相关的基因集。TMEM170B高表达与抗肿瘤免疫微环境相关,B细胞、T细胞、树突状细胞、单核细胞、M1巨噬细胞、中性粒细胞和自然杀伤细胞浸润高,而调节性T细胞和骨髓来源的抑制性细胞浸润低(均P < 0.05)。迫切需要确定胰腺癌治疗的临床预后生物标志物和靶向药物。在本研究中,阐明了跨膜蛋白170B(TMEM170B)在胰腺腺癌中的表达状态和预后价值。此外,TMEM170B作为一种肿瘤抑制基因,可诱导抗肿瘤免疫效应,包括增加免疫效应细胞的肿瘤浸润以及降低抑制性免疫分子和调节细胞的水平。因此,TMEM170B可被视为预防胰腺癌进展的新靶点。研究结果表明,TMEM170B低表达与PAAD预后不良显著相关,这可能为PAAD提供一个治疗靶点。