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单细胞RNA测序(scRNA-seq)和批量RNA测序(bulk RNA-seq)的综合分析表明,GPRC5A是胰腺癌中的一个重要预后基因,并且与胰腺癌中的B细胞浸润相关。

Integrated analysis of scRNA-seq and bulk RNA-seq reveals that GPRC5A is an important prognostic gene in pancreatic cancer and is associated with B-cell Infiltration in pancreatic cancer.

作者信息

Dong Chunlu, Ma Haidong, Mi Ningning, Fu Wenkang, Yi Jianfeng, Gao Long, Wang Haiping, Ren Yanxian, Lin Yanyan, Han Fangfang, Chen Zhou, Zhou Wence

机构信息

The First School of Clinical Medicine of Lanzhou University, Lanzhou, Gansu, China.

The First Hospital of Lanzhou University, Lanzhou, Gansu, China.

出版信息

Front Oncol. 2024 Apr 3;14:1283164. doi: 10.3389/fonc.2024.1283164. eCollection 2024.

DOI:10.3389/fonc.2024.1283164
PMID:38634049
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11021786/
Abstract

INTRODUCTION

Pancreatic cancer (PC) is a malignancy with poor prognosis. This investigation aimed to determine the relevant genes that affect the prognosis of PC and investigate their relationship with immune infiltration.

METHODS

: First, we acquired PC single-cell chip data from the GEO database to scrutinize dissimilarities in immune cell infiltration and differential genes between cancerous and adjacent tissues. Subsequently, we combined clinical data from TCGA to identify genes relevant to PC prognosis. Employing Cox and Lasso regression analyses, we constructed a multifactorial Cox prognostic model, which we subsequently confirmed. The prognostic gene expression in PC was authenticated using RT-PCR. Moreover, we employed the TIMER online database to examine the relationship between the expression of prognostic genes and T and B cell infiltration. Additionally, the expression of GPRC5A and its correlation with B cells infiltration and patient prognosis were ascertained in tissue chips using multiple immune fluorescence staining.

RESULTS

The single-cell analysis unveiled dissimilarities in B-cell infiltration between cancerous and neighboring tissues. We developed a prognostic model utilizing three genes, indicating that patients with high-risk scores experienced a more unfavorable prognosis. Immune infiltration analysis revealed a significant correlation among YWHAZ, GPRC5A, and B cell immune infiltration. In tissue samples, GPRC5A exhibited substantial overexpression and a robust association with an adverse prognosis, demonstrating a positive correlation with B cell infiltration.

CONCLUSION

GPRC5A is an independent risk factor in PC and correlated with B cell immune infiltration in PC. These outcomes indicated that GPRC5A is a viable target for treating PC.

摘要

引言

胰腺癌(PC)是一种预后较差的恶性肿瘤。本研究旨在确定影响胰腺癌预后的相关基因,并探讨它们与免疫浸润的关系。

方法

首先,我们从基因表达综合数据库(GEO)获取胰腺癌单细胞芯片数据,以研究癌组织和癌旁组织在免疫细胞浸润和差异基因方面的差异。随后,我们结合来自癌症基因组图谱(TCGA)的临床数据,以识别与胰腺癌预后相关的基因。通过Cox和Lasso回归分析,我们构建了一个多因素Cox预后模型,并随后进行了验证。使用逆转录聚合酶链反应(RT-PCR)验证胰腺癌中预后基因的表达。此外,我们利用TIMER在线数据库研究预后基因表达与T细胞和B细胞浸润之间的关系。另外,使用多重免疫荧光染色在组织芯片中确定G蛋白偶联受体C5A(GPRC5A)的表达及其与B细胞浸润和患者预后的相关性。

结果

单细胞分析揭示了癌组织和相邻组织在B细胞浸润方面的差异。我们利用三个基因建立了一个预后模型,表明高风险评分的患者预后更差。免疫浸润分析显示,14-3-3蛋白ζ(YWHAZ)、GPRC5A和B细胞免疫浸润之间存在显著相关性。在组织样本中,GPRC5A表现出大量过表达,并且与不良预后密切相关,与B细胞浸润呈正相关。

结论

GPRC5A是胰腺癌的一个独立危险因素,与胰腺癌中的B细胞免疫浸润相关。这些结果表明,GPRC5A是治疗胰腺癌的一个可行靶点。

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Subtyping for pancreatic cancer precision therapy.胰腺癌精准治疗的亚型分类
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B-Lymphocytes in the Pathophysiology of Pancreatic Adenocarcinoma.B淋巴细胞在胰腺腺癌病理生理学中的作用
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A DNA-Methylation-Driven Genes Based Prognostic Signature Reveals Immune Microenvironment in Pancreatic Cancer.基于 DNA 甲基化驱动基因的预后标志物揭示了胰腺癌中的免疫微环境。
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B Cell Receptor Signaling and Protein Kinase D2 Support Regulatory B Cell Function in Pancreatic Cancer.B 细胞受体信号和蛋白激酶 D2 支持胰腺癌中调节性 B 细胞的功能。
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