PPIC-labeled CAFs: Key players in neoadjuvant chemotherapy resistance for gastric cancer

IF 5 2区医学 Q2 Medicine

Translational Oncology Pub Date : 2024-08-07 DOI:10.1016/j.tranon.2024.102080

{"title":"PPIC-labeled CAFs: Key players in neoadjuvant chemotherapy resistance for gastric cancer","authors":"","doi":"10.1016/j.tranon.2024.102080","DOIUrl":null,"url":null,"abstract":"<div><h3>Background</h3><p>Gastric cancer (GC) is the fourth leading cause of cancer deaths, with advanced cases having a median survival of less than one year. Neoadjuvant chemotherapy (NCT) is vital but faces drug resistance issues, partly due to cancer-associated fibroblasts (CAFs). Yet, specific CAF subpopulations contributing to resistance are poorly understood.</p></div><div><h3>Methods</h3><p>Differentially expressed genes (DEGs) between chemosensitive and resistant GC patients were identified using GEO2R. Single-cell sequencing (scRNA-seq) identified CAF-related genes. Immunohistochemistry verified key genes in NCT-treated GC samples, analyzing their correlation with tumor regression grade (TRG) and clinicopathological characteristics.</p></div><div><h3>Results</h3><p><em>PPIC</em> as a gene highly expressed in CAFs was closely associated with NCT resistance in gastric cancer. Immunohistochemistry results revealed positivity for the expression of cyclophilin C (CypC), encoded by <em>PPIC</em>, in the 5-fluorouracil and cisplatin NCT resistant and -sensitive groups of gastric cancer patients at rates of 69.7 % (76/109) and 43.6 % (24/55), respectively (<em>p</em> < 0.001). The high expression of CypC in CAFs was positively correlated to tumor size (<em>p</em> = 0.025), T stage (<em>p</em> = 0.004), TNM stage (<em>p</em> = 0.004), and vascular invasion (<em>p</em> = 0.027). In cancer cells the expression of CypC was associated with OS (<em>p</em> = 0.026). However, in CAFs, CypC expression was not related to OS (<em>p</em> = 0.671).</p></div><div><h3>Conclusions</h3><p><em>PPIC</em>-labeled CAF subgroups are related to NCT resistance and poor prognosis in GC and they may cause drug resistance through signaling pathways such as glucose metabolism and extracellular matrix remodeling. However, the exact mechanism behind the involvement of <em>PPIC</em>-labeled CAF in drug resistance of GC requires further study.</p></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":null,"pages":null},"PeriodicalIF":5.0000,"publicationDate":"2024-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1936523324002079/pdfft?md5=92c45df01dec332f5d2062b8f4061b76&pid=1-s2.0-S1936523324002079-main.pdf","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Translational Oncology","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S1936523324002079","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"Medicine","Score":null,"Total":0}

引用次数: 0

Abstract

Background

Gastric cancer (GC) is the fourth leading cause of cancer deaths, with advanced cases having a median survival of less than one year. Neoadjuvant chemotherapy (NCT) is vital but faces drug resistance issues, partly due to cancer-associated fibroblasts (CAFs). Yet, specific CAF subpopulations contributing to resistance are poorly understood.

Methods

Differentially expressed genes (DEGs) between chemosensitive and resistant GC patients were identified using GEO2R. Single-cell sequencing (scRNA-seq) identified CAF-related genes. Immunohistochemistry verified key genes in NCT-treated GC samples, analyzing their correlation with tumor regression grade (TRG) and clinicopathological characteristics.

Results

PPIC as a gene highly expressed in CAFs was closely associated with NCT resistance in gastric cancer. Immunohistochemistry results revealed positivity for the expression of cyclophilin C (CypC), encoded by PPIC, in the 5-fluorouracil and cisplatin NCT resistant and -sensitive groups of gastric cancer patients at rates of 69.7 % (76/109) and 43.6 % (24/55), respectively (p < 0.001). The high expression of CypC in CAFs was positively correlated to tumor size (p = 0.025), T stage (p = 0.004), TNM stage (p = 0.004), and vascular invasion (p = 0.027). In cancer cells the expression of CypC was associated with OS (p = 0.026). However, in CAFs, CypC expression was not related to OS (p = 0.671).

Conclusions

PPIC-labeled CAF subgroups are related to NCT resistance and poor prognosis in GC and they may cause drug resistance through signaling pathways such as glucose metabolism and extracellular matrix remodeling. However, the exact mechanism behind the involvement of PPIC-labeled CAF in drug resistance of GC requires further study.

查看原文本刊更多论文

PPIC标记的CAFs：胃癌新辅助化疗耐药性的关键因素

背景：胃癌（GC）是导致癌症死亡的第四大原因，晚期病例的中位生存期不到一年。新辅助化疗（NCT）至关重要，但也面临耐药性问题，部分原因是癌症相关成纤维细胞（CAFs）。然而，人们对导致耐药性的特定 CAF 亚群知之甚少：方法：使用 GEO2R 鉴定化疗敏感和耐药 GC 患者之间的差异表达基因（DEGs）。单细胞测序（scRNA-seq）确定了CAF相关基因。免疫组化验证了NCT处理的GC样本中的关键基因，分析了它们与肿瘤回归分级（TRG）和临床病理特征的相关性：结果：CAFs中高表达的PPIC基因与胃癌的NCT耐药性密切相关。免疫组化结果显示，PPIC编码的环嗜蛋白C（CypC）在5-氟尿嘧啶和顺铂NCT耐药组和敏感组胃癌患者中的阳性表达率分别为69.7%（76/109）和43.6%（24/55）（P＜0.001）。CypC在CAFs中的高表达与肿瘤大小（p = 0.025）、T分期（p = 0.004）、TNM分期（p = 0.004）和血管侵犯（p = 0.027）呈正相关。在癌细胞中，CypC的表达与OS相关（p = 0.026）。然而，在CAFs中，CypC的表达与OS无关（p = 0.671）：结论：PPIC标记的CAF亚群与NCT耐药和GC的不良预后有关，它们可能通过糖代谢和细胞外基质重塑等信号通路导致耐药。然而，PPIC标记的CAF参与GC耐药的确切机制还需要进一步研究。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Translational Oncology ONCOLOGY-

CiteScore

8.40

自引率

2.00%

发文量

314

审稿时长

54 days

期刊介绍： Translational Oncology publishes the results of novel research investigations which bridge the laboratory and clinical settings including risk assessment, cellular and molecular characterization, prevention, detection, diagnosis and treatment of human cancers with the overall goal of improving the clinical care of oncology patients. Translational Oncology will publish laboratory studies of novel therapeutic interventions as well as clinical trials which evaluate new treatment paradigms for cancer. Peer reviewed manuscript types include Original Reports, Reviews and Editorials.