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全面分析肌球蛋白 4 在胰腺癌中的临床预后和分子免疫特征。

Comprehensive analysis of clinical prognosis and molecular immune characterization of tropomyosin 4 in pancreatic cancer.

机构信息

Department of Nephrology, Tianjin Haihe Hospital, Tianjin, 300350, China.

Tianjin Third Central Hospital, 83 Jintang Road, Hedong District, Tianjin, 300170, China.

出版信息

Invest New Drugs. 2021 Dec;39(6):1469-1483. doi: 10.1007/s10637-021-01128-z. Epub 2021 May 13.

Abstract

Pancreatic cancer (PC) is one of the most lethal human solid malignancies with devastating prognosis, making biomarker detection considerably important. Immune infiltrates in microenvironment is associated with patients' survival in PC. The role of Tropomyosin 4 (TPM4) gene in PC has not been reported. Our study first identifies TPM4 expression and its potential biological functions in PC. The potential oncogenic roles of TPM4 was examined using the datasets of TCGA (The cancer genome atlas) and GEO (Gene expression omnibus). We investigated the clinical significance and prognostic value of TPM4 gene based on The Gene Expression Profiling Interactive Analysis (GEPIA) and survival analysis. TIMER and TISIDB databases were used to analyze the correlations between TPM4 gene and tumor-infiltrating immune cells. We found that the expression level of TPM4 was upregulated in PC malignant tissues with the corresponding normal tissues as controls. High TPM4 expression was correlated with the worse clinicopathological features and poor prognosis in PC cohorts. The positive association between TPM4 expression and tumor-infiltrating immune cells was identified in tumor microenvironment (TME). Moreover, functional enrichment analysis suggested that TPM4 might participate in cell adhesion and promote tumor cell migration. This is the first comprehensive study to disclose that TPM4 may serve as a novel prognostic biomarker associating with immune infiltrates and provide a potential therapeutic target for the treatment of PC.

摘要

胰腺癌(PC)是人类最致命的实体恶性肿瘤之一,预后极差,因此生物标志物的检测显得尤为重要。肿瘤微环境中的免疫浸润与患者的生存有关。Tropomyosin 4(TPM4)基因在 PC 中的作用尚未见报道。我们的研究首次确定了 TPM4 在 PC 中的表达及其潜在的生物学功能。利用 TCGA(癌症基因组图谱)和 GEO(基因表达综合数据库)数据集,研究了 TPM4 基因的潜在致癌作用。我们基于基因表达谱交互分析(GEPIA)和生存分析,研究了 TPM4 基因的临床意义和预后价值。TIMER 和 TISIDB 数据库用于分析 TPM4 基因与肿瘤浸润免疫细胞之间的相关性。我们发现,与相应的正常组织相比,PC 恶性组织中 TPM4 的表达水平上调。高 TPM4 表达与 PC 队列中较差的临床病理特征和预后相关。在肿瘤微环境(TME)中,确定了 TPM4 表达与肿瘤浸润免疫细胞之间的正相关关系。此外,功能富集分析表明,TPM4 可能参与细胞黏附并促进肿瘤细胞迁移。这是首次全面研究表明,TPM4 可能作为一个与免疫浸润相关的新的预后生物标志物,并为 PC 的治疗提供一个潜在的治疗靶点。

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