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TNFSF9 是胰腺癌的预后生物标志物,并与免疫浸润相关。

TNFSF9 Is a Prognostic Biomarker and Correlated with Immune Infiltrates in Pancreatic Cancer.

机构信息

Departments of Gastroenterology, Chongqing Medical University First Affiliated Hospital, Chongqing, 400016, China.

Departments of cardiovascular, Zigong First People's Hospital, Zigong, 643000, Sichuan, China.

出版信息

J Gastrointest Cancer. 2021 Mar;52(1):150-159. doi: 10.1007/s12029-020-00371-6.

Abstract

BACKGROUND

TNFSF9 gene has been found to play an anti-tumor role and regulate the function of immune cells. However, the prognostic role of TNFSF9 in pancreatic cancer and its relationship with immune cell infiltration have not been studied.

METHODS

We used Oncomine, UALCAN, and GEPIA databases to analyze the expression of TNFSF9 in pancreatic cancer. We used Kaplan-Meier plotters, GEPIA, and UALCAN to evaluate the effect of TNFSF9 on clinical prognosis. We further used TIMER to study the correlation between TNFSF9 and cancer immune infiltrate cells. In addition, we used GEPIA to analyze the correlation between TNFSF9 expression and gene markers of immune infiltrate cells.

RESULTS

TNFSF9 mRNA expression level was remarkably increased in pancreatic cancer than that in normal tissues (both P < 0.05). In addition, high TNFSF9 expression was significantly related to poor overall survival (OS) and relapse-free survival (RFS) in pancreatic cancer (OS HR = 2.02, P = 0.0012; RFS HR = 2.63, P = 0.022). Moreover, high TNFSF9 expression in pancreatic cancer patients was associated with worse OS in stage 1 to 2 but not stage 3 and stage 4. Specifically, TNFSF9 expression and CD8 T cell infiltration of pancreatic cancer was negatively correlated. TNFSF9 expression showed strong correlations with M1 macrophages in pancreatic cancer.

CONCLUSIONS

Our results suggest that TNFSF9 is associated with prognosis and CD8 T cell infiltration levels in patients with pancreatic cancer. Further, TNFSF9 expression potentially contributes to the modulation of M1 polarization of macrophages. These findings indicate that TNFSF9 can be serves as a prognostic biomarker in determining the prognosis of pancreatic cancer and is associated with different types of phenotypes of immune cell infiltration.

摘要

背景

TNFSF9 基因已被发现具有抗肿瘤作用,并调节免疫细胞的功能。然而,TNFSF9 在胰腺癌中的预后作用及其与免疫细胞浸润的关系尚未得到研究。

方法

我们使用 Oncomine、UALCAN 和 GEPIA 数据库分析了 TNFSF9 在胰腺癌中的表达。我们使用 Kaplan-Meier plotters、GEPIA 和 UALCAN 评估了 TNFSF9 对临床预后的影响。我们进一步使用 TIMER 研究了 TNFSF9 与癌症免疫浸润细胞之间的相关性。此外,我们使用 GEPIA 分析了 TNFSF9 表达与免疫浸润细胞基因标志物之间的相关性。

结果

与正常组织相比,TNFSF9 mRNA 表达水平在胰腺癌中显著增加(均 P<0.05)。此外,高 TNFSF9 表达与胰腺癌患者的总生存期(OS)和无复发生存期(RFS)显著相关(OS HR=2.02,P=0.0012;RFS HR=2.63,P=0.022)。此外,在胰腺癌患者中,TNFSF9 的高表达与分期为 1 至 2 期但不是 3 期和 4 期的 OS 较差相关。具体而言,TNFSF9 表达与胰腺癌细胞中 CD8 T 细胞浸润呈负相关。TNFSF9 表达与胰腺癌细胞中 M1 巨噬细胞呈强相关。

结论

我们的研究结果表明,TNFSF9 与胰腺癌患者的预后和 CD8 T 细胞浸润水平相关。此外,TNFSF9 表达可能有助于调节巨噬细胞的 M1 极化。这些发现表明,TNFSF9 可以作为预测胰腺癌预后的生物标志物,并与不同类型的免疫细胞浸润表型相关。

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