FN1 表达水平高与胃癌进展相关。

High FN1 expression correlates with gastric cancer progression.

机构信息

The First School of Clinical Medicine of Lanzhou University, Lanzhou, Gansu, China; Department of General Surgical, Gansu Provincial Hospital, Lanzhou, Gansu, China; The First School of Clinical Medical, Gansu University of Chinese Medicine, Lanzhou, Gansu, China.

Department of Pathology, Gansu Provincial Hospital, Lanzhou, Gansu, China.

出版信息

Pathol Res Pract. 2022 Nov;239:154179. doi: 10.1016/j.prp.2022.154179. Epub 2022 Oct 18.

DOI:10.1016/j.prp.2022.154179

PMID:36274380

Abstract

OBJECTIVE

High stromal ratio of gastric cancer is associated with a poor prognosis. Fibronectin 1(FN1) is the main component of gastric cancer stroma. The focus of this research was to investigate the FN1 express pattern, the connection between FN1 expression, clinicopathological parameters, survival, and mismatch repair genes (MMR) or immune checkpoints in gastric cancer patients.

METHODS

Eighty-six paired stomach cancer tissues, neighboring normal tissues, and eight independent gastric cancer tissues were used to create 180 points tissue microarrays. The association between epithelial fibronectin (E-FN1), stromal fibronectin (S-FN1) expression, and clinical characteristics was analyzed using the chi-square test or Fisher's exact test, and the survival analysis curve was analyzed using the log-rank test, followed by univariate and multivariate Cox regression. The correlation between FN1 and MMR or immune checkpoints was analyzed by Spearman correlation.

RESULTS

FN1 is mainly expressed in gastric cancer tissues, with low or no expression in adjacent normal tissues. In tumor tissues, FN1 is mostly distributed in the stroma. High E-FN1 expression was associated with a decreased overall survival (OS), while S-FN1 expression did not. High S-FN1 expression correlated with older age (P<0.001), higher pathological grade (P<0.001), pathological type (P<0.001), vessel/lymphatic invasion (P<0.001), advanced T stage (P=0.001), N stage (P=0.01), and worse TNM stage(P = 0.033). FN1 expression was not associated with MMR or immune checkpoints (MLH1, MSH2, MSH6, PDL1, PD1, PMS2, and CD8).

CONCLUSIONS

High E-FN1 expression predicted poor OS, while S-FN1 is associated with gastric cancer progression.

摘要

目的

胃癌间质中高间质比例与预后不良有关。纤维连接蛋白 1（FN1）是胃癌间质的主要成分。本研究的重点是探讨 FN1 的表达模式、FN1 表达与临床病理参数、生存以及胃癌患者错配修复基因（MMR）或免疫检查点之间的关系。

方法

使用 86 对胃癌组织、相邻正常组织和 8 个独立的胃癌组织制作了 180 个组织微阵列。使用卡方检验或 Fisher 精确检验分析上皮纤维连接蛋白（E-FN1）、间质纤维连接蛋白（S-FN1）表达与临床特征的关系，采用对数秩检验分析生存分析曲线，然后进行单因素和多因素 Cox 回归分析。采用 Spearman 相关分析 FN1 与 MMR 或免疫检查点的相关性。

结果

FN1 主要在胃癌组织中表达，在相邻正常组织中低表达或无表达。在肿瘤组织中，FN1 主要分布在基质中。E-FN1 高表达与总生存（OS）降低相关，而 S-FN1 表达则无此关联。S-FN1 高表达与年龄较大（P<0.001）、病理分级较高（P<0.001）、病理类型（P<0.001）、血管/淋巴管侵犯（P<0.001）、T 分期较晚（P=0.001）、N 分期（P=0.01）和更差的 TNM 分期（P=0.033）相关。FN1 表达与 MMR 或免疫检查点（MLH1、MSH2、MSH6、PDL1、PD1、PMS2 和 CD8）无关。