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胰腺癌种族差异相关的肿瘤免疫微环境差异

Tumor Immune Microenvironment Differences Associated With Racial Disparities in Pancreatic Cancer.

作者信息

Gao Zachary, Azar Joseph, Erstad Derek, Sun Zequn, Janakiraman Harinarayanan, Chung Dongjun, Lewin David, Lee Hyun-Sung, Van Buren George, Fisher William, Rubinstein Mark P, Camp E Ramsay

机构信息

Michael E. DeBakey Department of Surgery, Baylor College of Medicine, Houston, Texas.

The Pelotonia Institute for Immuno-Oncology, Ohio State University Comprehensive Cancer Center, Columbus, Ohio.

出版信息

J Surg Res. 2025 Mar;307:21-32. doi: 10.1016/j.jss.2025.01.005. Epub 2025 Feb 18.

Abstract

INTRODUCTION

Racial differences in antitumoral immunity have been identified in a variety of cancers and may contribute to survival disparities, but limited data exist exploring the molecular differences in pancreatic adenocarcinoma (PDAC). Using racially diverse PDAC datasets, we explored biologic differences that may drive disparities between African American (AA) and European American (EA) PDAC patients.

METHODS

Genomic PDAC mutational data was analyzed for mutational differences based on race. In a separate cohort, surgical PDAC specimens were processed for both tissue microarray and multiplex gene expression analysis using NanoString.

RESULTS

Of the 4679 patient samples in the mutational dataset, AA PDAC patients had significantly more TP53 mutations compared to the EA cohort. The tissue microarray included 12 AA and 41 EA surgically resected treatment-naive PDAC samples. NanoString analysis revealed significant differences between AA and EA groups in immunologic gene annotations (P < 0.05).

CONCLUSIONS

In the present study, we demonstrated that across racially diverse datasets, there exist molecular and microenvironmental differences between AA and EA patients that may contribute to cancer survival disparities. Defining molecular differences underlying PDAC racial disparities is an essential step in advancing care and improving outcomes for AA patients that suffer worse survival across cancer types.

摘要

引言

在多种癌症中已发现抗肿瘤免疫存在种族差异,这可能导致生存差异,但探索胰腺腺癌(PDAC)分子差异的数据有限。利用种族多样的PDAC数据集,我们探究了可能导致非裔美国(AA)和欧美裔(EA)PDAC患者之间差异的生物学差异。

方法

分析基因组PDAC突变数据,以确定基于种族的突变差异。在另一个队列中,对手术切除的PDAC标本进行处理,用于制作组织芯片,并使用NanoString进行多重基因表达分析。

结果

在突变数据集中的4679例患者样本中,与EA队列相比,AA PDAC患者的TP53突变显著更多。组织芯片包括12例AA和41例EA手术切除的未经治疗的PDAC样本。NanoString分析显示,AA组和EA组在免疫基因注释方面存在显著差异(P < 0.05)。

结论

在本研究中,我们证明在种族多样的数据集中,AA和EA患者之间存在分子和微环境差异,这可能导致癌症生存差异。确定PDAC种族差异背后的分子差异是推进护理并改善在各类癌症中生存较差的AA患者预后的关键一步。

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