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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.

SUBMITTER: Lin CH

PROVIDER: S-EPMC9632826 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

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

Lin Chih-Hung CH Chuang Han-Ni HN Hsiao Tzu-Hung TH Kumar V Bharath VB Hsu Chiung-Hung CH Huang Chih-Yang CY Lee Li-Wen LW Mao Chien-Lin CL Ko Jiunn-Liang JL Hsu Chung-Ping CP

PloS one 20221103 11

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- ...[more]

PMID: 36327302

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Project description:BackgroundEsophageal squamous cell carcinoma (ESCC) represents a frequent cancer with a poor prognosis. Altered glucose metabolism contributes factor to ESCC progression. In our previous study, signal sequence receptor subunit delta (SSR4) was included in an ESCC prognostic model; however, the mechanisms underlying SSR4 implication in ESCC remain ambiguous. Accordingly, we aim to determine the interconnection between SSR4 expression and clinical characteristics of ESCC.MethodsThis differential expression and prognostic significance of SSR4 was performed using bulk RNA-seq data and 110 patients with complete follow-up information. The ESCC cell subsets with the highest gene expression levels were identified with single-cell data. Gene function and enrichment, immune infiltration, cell communication, and molecular docking analyses were performed.ResultsUnlike adjacent non-cancerous tissues, SSR4 was overexpressed in ESCC tissues, validated by both reverse transcription-qPCR and IHC staining. SSR4 expression was related to the N stage, lymph node metastasis, and AJCC TNM classification stage. Patients exhibiting low SSR4 expression had a more favorable prognosis. The highest SSR4 expression was recognized in tumor plasma cells. Continued exploration of immune infiltration highlighted a close association between SSR4 gene expression and the infiltration of immune cells such as plasma cells. On dividing cells into SSR4-positive and -negative groups, CellChat analysis indicated that SSR4 may regulate the interactions that existed between ESCC tumor plasma cells and the tumor microenvironment (TME) by modulating the MIF/CD74/CXCR4 axis.ConclusionThe SSR4 gene may have significant relevance with clinical pathological factors, and play a critical role in the regulation of tumor microenvironment of ESCC patients. Overall, SSR4 may be a promising ESCC biomarker with prospective applicability in clinical diagnosis as well as the development of targeted treatment approaches in patients of ESCC.

Project description:Background and aimsMicroRNAs including miR146a have a regulatory role on the expression of genes and act with binding to 3'-UTR region of the genes. Cyclooxygenase-2 (COX-2) is involved in carcinogenesis as an inflammatory marker, and microRNA-146a (miR-146a) as a negative regulatory factor. We aimed to evaluate miR146a expression as a prognostic or diagnostic biomarker for esophageal squamous cell carcinoma (ESCC) and also an association between miR146a and COX2 expression.Materials and methodsWe quantified the level of miR-146a and COX-2 expression in cancerous and adjacent normal tissue samples obtained from 34 patients with ESCC, using real-time-PCR. Statistical analyses were conducted using one-sample t-test. Receiver-operating characteristic (ROC) curve and Kaplan-Meier analysis were applied to assay miR146a as a diagnostic and prognostic marker, respectively, during 4 years of the study. Furthermore, the Cox regression model was performed to assay the hazard ratio (HR). The association between miR-146a and COX2 expression level in ESCC patients was evaluated by nonparametric Spearman's rho analysis.ResultsThe results revealed a reduction of miR-146a expression in 50% of cancerous tissue when compared with adjacent normal regions (P-value=0.127). COX-2 expression in 80% of ESCC patients was higher than in the controls (P-value=0.001). Overall, in 60% of cases, direct association was seen between microRNA-146a and COX-2 expression level (correlation coefficient= 0.438, P-value=0.011). COX2 can be considered as a diagnostic biomarker (AUC=0.834, sensitivity=72%, specificity =83%, P-value<0.0001) but miR146a cannot be considered as a diagnostic biomarker (AUC=0.553, sensitivity=88%, specificity =28%, P-value=0.453). Survival analysis by Kaplan-Meier method showed miR146a and COX2 expression can be probably considered as prognostic biomarkers for ESCC because patients with high expression of miR146a had 7 months shorter life span and patients with low expression of COX2 had 8 months shorter life span.ConclusionCOX2 expression is a diagnostic biomarker. MiR-146a and COX2 expression can probably be considered as prognostic biomarkers for survival in ESCC.

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

Publications

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

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