AGR2 expression as a predictive biomarker for therapy response in esophageal squamous cell carcinoma

Abstract

Despite multidisciplinary therapy, the prognosis is poor for esophageal squamous cell carcinoma (ESCC). In the locally advanced stage, neoadjuvant chemoradiotherapy (nCRT) followed by surgery could provide survival benefits to some patients. Here, we aimed to identify for tumor therapy response a biomarker based on RNA sequencing. We collected endoscopic biopsies of 32 ESCC patients, who were divided according to nCRT response, into two groups: the complete response group (n = 13) and the non-complete response group (n = 19). RNA-sequencing data showed that 464 genes were differentially expressed. Increased in non-complete response group, 4 genes increased expressions were AGR2 (anterior gradient 2), GADD45B (growth arrest and DNA damage inducible beta), PPP1R15A (protein phosphatase 1 regulatory subunit 15A) and LRG1 (leucine rich alpha-2-glycoprotein 1). The areas under the curve (AUC) of the AGR2 gene was 0.671 according to read counts of RNA-seq and therapy response of nCRT. In vitro study showed that apoptosis cell was significantly increased in the AGR2-knockdown TE-2 cell line treated with cisplatin and 5-Fluorouracil (5-FU), when compared with si-control. Results suggest that in ESCC, the AGR2 gene is a promising and predictive gene marker for the response to anti-tumor therapy.

A phase 2 trial of peri-operative avelumab and chemotherapy for locally advanced gastro-esophageal adenocarcinoma: Association of AGR2/AP-1 complex CD8 T-cells and M2-Tumour Associated Macrophages with treatment response

“…Beyond these ndings, we have also demonstrated subtle transcriptomic differences among T cell subpopulations when stratifying patients according to disease response to neoadjuvant therapy. Previous studies have explored the prognostic bene t of AGR2 with upregulation being associated with poorer oncological outcomes in patients with squamous cell carcinoma of the esophagus 45 . This outcome is thought to be due to AGR2 interaction with disulphide-dependant complexes including MUC-5 that in turn promotes tumoral proliferation and cell migration in adenocarcinoma 46 .…”

AGR2: The Covert Driver and New Dawn of Hepatobiliary and Pancreatic Cancer Treatment

“…And subsequent studies demonstrated its role in promoting tumor progression in cancer cells associated with sex hormone receptors [71,86]. Further research has confirmed that AGR2 can be overexpressed and exert pro-cancer functions in various solid cancers [24], ranging from adenocarcinomas to squamous carcinomas, including breast adenocarcinomas [87], pancreatic adenocarcinomas [88], esophageal adenocarcinomas [89], prostate adenocarcinomas [78], esophageal squamous cell carcinomas [90], and HCC [12].…”

“…AGR2 has consistently emerged as a potential therapeutic target in colon cancer from various perspectives [15,126,143]. AGR2 is overexpressed in esophageal squamous cell carcinoma and that AGR2 expression may serve as a biomarker for predicting the response to treatment in esophageal squamous cell carcinoma and as a potential therapeutic target for patients with P53 wild-type esophageal squamous cell carcinoma [90,144]. Targeting the link between ovarian cancer [145], esophageal squamous cell carcinoma [90], and other cancers with AGR2 immunity, we can hypothesize that AGR2 influences the immune microenvironment of patients, suggesting a potential undiscovered link between the two that may impact patient prognosis.…”

Molecular Signatures Integral to Natural Reprogramming in the Pigment Epithelium Cells after Retinal Detachment in Pleurodeles waltl

“…AGR2 performs the function of the molecular chaperone, which regulates the folding, trafficking, and assembly of cysteine-rich transmembrane receptors. It was also implicated in inflammation and cancer progression and in the regulation of the cell migration and transformation [139] by suppressing tumor inhibitor p53 [140]. The NACA gene was shown in the list of down-regulated genes at 7 days of RPE reprogramming.…”