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

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 bi...

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Bibliographic Details
Published in:PloS one 2022-11, Vol.17 (11), p.e0276990-e0276990
Main Authors: Lin, Chih-Hung, Chuang, Han-Ni, Hsiao, Tzu-Hung, Kumar, V. Bharath, Hsu, Chiung-Hung, Huang, Chih-Yang, Lee, Li-Wen, Mao, Chien-Lin, Ko, Jiunn-Liang, Hsu, Chung-Ping
Format: Article
Language:English
Subjects:
5-Fluorouracil
Agr2 gene
Analysis
Antimitotic agents
Antineoplastic agents
Apoptosis
Biomarkers
Biopsy
Cancer therapies
Care and treatment
Chemoradiotherapy
Chemotherapy
Cisplatin
Deoxyribonucleic acid
Diagnosis
DNA
DNA damage
Dosage and administration
Endoscopy
Esophageal cancer
Gene expression
Gene sequencing
Genes
Genetic aspects
Genetic markers
Glycoproteins
Leucine
Medical prognosis
Neoadjuvant therapy
Patient outcomes
Patients
Phosphoprotein phosphatase
Polymerase chain reaction
Prostate cancer
Protein phosphatase
Proteins
Radiation therapy
Reagents
Ribonucleic acid
RNA
RNA sequencing
Squamous cell carcinoma
Surgery
Therapy
Tumors
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Summary: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.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0276990