肿瘤细胞治疗研究
英文原题：Transmembrane Protein 170B is a Prognostic Biomarker and Associated With Immune Infiltrates in Pancreatic Adenocarcinoma.
Transmembrane Protein 170B is a Prognostic Biomarker and Associated With Immune Infiltrates in Pancreatic Adenocarcinoma.
TMEM170B低表达与低分化相关（p = 0.014）。
背景：胰腺腺癌（PAAD）是最常见的癌症类型之一，预后较差。据报道，跨膜蛋白170B（TMEM170B）可抑制乳腺癌增殖、转移和肿瘤发生，并与预后相关。然而，其在PAAD中的作用及潜在分子机制尚待研究。患者与方法：我们对来自基因表达综合数据库（GEO）和癌症基因组图谱（TCGA）数据库的RNA测序数据进行了全面分析，以确定TMEM170B的表达。采用免疫染色和实时聚合酶链反应（RT-PCR）检测人胰腺癌细胞系和组织标本中TMEM170B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。结果：TCGA和GEO数据集分析显示，PAAD组织样本中TMEM170B的表达显著低于非肿瘤组织，免疫组化和RT-PCR进一步证实了这一点。TMEM170B低表达与低分化相关（p = 0.014）。多因素分析确定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参与免疫相关基因集，包括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，表现为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NK 细胞高浸润，以及Tregs和髓源性抑制细胞低浸润（均p < 0.05）。通俗语言总结：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作为抑癌基因，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性细胞的水平。因此，TMEM170B可被视为预防胰腺癌进展的新靶点。结论：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提供治疗靶点。
Background: 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. Patients and methods: 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. Results: 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 ( p = 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; p = 0.049] and disease-free survival (HR = 0.19, 95% CI = 0.04-0.910; p = 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 p < 0.05). Plain Language Summary: 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. Conclusion: The findings suggest that low TMEM170B expression is remarkably correlated with poor PAAD prognosis, which might provide a therapeutic target for PAAD.
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