PRRX1 promotes lymph node metastasis of gastric cancer by regulating epithelial-mesenchymal transition

Abstract

Background: Gastric cancer has multiple metastasis pathways, of which lymph node metastasis plays a dominant role. However, the specific mechanism of lymph node metastasis is still not unclear. Methods: The bioinformatics technology was utilized to mine gene chip data related to gastric cancer and Epithelial-Mesenchymal Transition (EMT) in a high-throughput gene expression database (Gene Expression Omnibus, GEO), we screened out all genes that have differential expression levels in gastric cancer tissues and in adjacent normal gastric mucosa tissues. The corresponding function package of R language software were performed for gene annotation and cluster analysis, then enrichment analysis of genes with differential expression and protein interaction network diagram for correlation analysis were performed, we finally screened out the paired related homeobox 1 gene (PRRX1) related to EMT. Next, we collected 65 metastatic lymph node samples and 93 gastric cancer tissue samples. The expression levels of PRRX1 and EMT-related protein E-cadherin (E-ca) and vimentin (Vim) in gastric cancer tissues and metastatic lymph node tissues were determined by immunohistochemistry (IHC) staining of streptavidin-peroxidase (SP). The expression differences of PRRX1, E-ca and Vim in gastric cancer tissues and metastatic lymph node tissues as well as the correlation were analyzed by the experimental data, and the clinical significance was analyzed in combination with the clinicopathological data. Results: The PRRX1 expression levels in gastric cancer tissues are significantly higher than that in adjacent normal gastric mucosa tissues. The positive expression rates of PRRX1, Vim and E-ca in gastric cancer and in metastatic lymph node tissues were significantly different. Comparing with that in gastric cancer, expression of PRRX1 and Vim was significantly down-regulated, and E-ca expression was significantly up-regulated in metastatic lymph nodes. Conclusion: PRRX1 may promote lymph node metastasis of gastric cancer by regulating EMT, and then affect the prognosis of patients. PRRX1 may be used as a new biological indicator to predict or prevent lymph node metastasis in gastric cancer.

Sqstm1/P62 as a Prognostic Marker Promotes the Progression of Gastric Cancer Through Epithelial-Mesenchymal Transition

“…In metastatic prostate cancer cells, high expression of p62 promotes EMT, resulting in enhanced abilities for proliferation, invasion, and migration [28]. In previous studies by our research group, the expression levels of EMT markers in GC with lymph node metastasis were investigated, revealing lower levels of E-cadherin expression and relatively higher levels of vimentin expression [29]. Through our experiments, we have also validated the role of p62 in GC EMT.…”

SQSTM1/p62 promotes the progression of gastric cancer through epithelial-mesenchymal transition

“…In cells, p62 can affect the activity of EMT-related factors [ 41 ]. p62 has been identified as a regulator of EMT induction, invasion and metastasis in esophageal squamous cell carcinoma [ 42 ].In previous studies by our research group, the expression levels of EMT markers in GC with lymph node metastasis were investigated, revealing lower levels of E-cadherin expression and relatively higher levels of vimentin expression [ 43 ]. Through our experiments, we have also validated the role of p62 in GC EMT.…”

Design of an In Vitro Model for Epithelial-to-Mesenchymal Transition in Gastric Cancer

“…The EMT has also been shown to be an important mechanism contributing to the metastasis and progression of cancer, especially in gastric cancer (Pastushenko and Blanpain 2019;Yao et al 2021). Recently, Brachyury has been identified as a significant regulator of EMT, modulating the expression of E-cadherin and Vimentin in various cells.…”