Anterior gradient 2 profiling in Barrett columnar epithelia and adenocarcinoma

Pizzi, Marco; Fassan, Matteo; Realdon, Stefano; Balistreri, Mariangela; Battaglia, Giorgio; Giacometti, Cinzia; Zaninotto, Giovanni; Zagonel, Vittorina; Boni, Michele De

doi:10.1016/j.humpath.2012.01.004

Cited by 7 publications

(7 citation statements)

References 39 publications

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“…Similarly, HSPA5 was found to be expressed in both EAC and gastric epithelium. These findings agree with previous reports (44–48). HSPA5 is thought to play a key role in the regulation of the unfolded-protein response and this expression pattern may reflect an increased protein chaperone demand in secretory cells (48, 49).…”

Section: Discussionsupporting

confidence: 94%

Quantitative Shotgun Proteomics Unveils Candidate Novel Esophageal Adenocarcinoma (EAC)-specific Proteins

O’Neill

Pak

Pairo-Castineira

et al. 2017

Molecular & Cellular Proteomics

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Esophageal cancer is the eighth most common cancer worldwide and the majority of patients have systemic disease at presentation. Esophageal adenocarcinoma (OAC), the predominant subtype in western countries, is largely resistant to current chemotherapy regimens. Selective markers are needed to enhance clinical staging and to allow targeted therapies yet there are minimal proteomic data on this cancer type. After histological review, lysates from OAC and matched normal esophageal and gastric samples from seven patients were subjected to LC MS/MS after tandem mass tag labeling and OFFGEL fractionation. Patient matched samples of OAC, normal esophagus, normal stomach, lymph node metastases and uninvolved lymph nodes were used from an additional 115 patients for verification of expression by immunohistochemistry (IHC).Over six thousand proteins were identified and quantified across samples. Quantitative reproducibility was excellent between technical replicates and a moderate correlation was seen across samples with the same histology. The quantitative accuracy was verified across the dynamic range for seven proteins by immunohistochemistry (IHC) on the originating tissues. Multiple novel tumor-specific candidates are proposed and EPCAM was verified by IHC.This shotgun proteomic study of OAC used a comparative quantitative approach to reveal proteins highly expressed in specific tissue types. Novel tumor-specific proteins are proposed and EPCAM was demonstrated to be specifically overexpressed in primary tumors and lymph node metastases compared with surrounding normal tissues. This candidate and others proposed in this study could be developed as tumor-specific targets for novel clinical staging and therapeutic approaches.

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Section: Discussionsupporting

confidence: 94%

Quantitative Shotgun Proteomics Unveils Candidate Novel Esophageal Adenocarcinoma (EAC)-specific Proteins

O’Neill

Pak

Pairo-Castineira

et al. 2017

Molecular & Cellular Proteomics

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Section: Discussionmentioning

confidence: 99%

“…The first is the worldwide most common malignant tumor of the esophagus; however, the incidence of AC has increased dramatically in the past 3 decades and now constitutes more than 50% of all esophageal carcinomas. [40][41][42][43][44][45][46][47][48][49][50] SCC and AC of the esophagus have different biological behavior, and this influences treatment choices. Nevertheless, in studies comparing the effectiveness of neoadjuvant CRT than surgery alone, investigators generally include either SCC patients alone or both histological types.…”

Section: Esophageal Cancermentioning

confidence: 99%

Pathological Tumor Regression Grade Classifications in Gastrointestinal Cancers: Role on Patients’ Prognosis

et al. 2019

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Preoperative chemotherapy or combined radiotherapy and chemotherapy (CRT), followed by surgery, represents the standard approach for locally advanced esophageal, gastric, and rectal carcinomas. To adequately evaluate the effects of neoadjuvant CRT in the resection specimens, several histopathologic tumor regression grade (TRG) scoring systems have been introduced into clinical practice. The primary goal of these TRG systems relies on a correct prognostic stratification of patients in the attempt to help clinical decision-making and influence surgical strategies, postoperative adjuvant therapies, and surveillance intensity. However, most TRG systems suffer from poor reproducibility and low interobserver concordance rates. Many efforts have been made in the identification of alternative, robust, simple, and universally accepted TRG scoring systems, which would help in the comparison of different treatment strategies and in the standardization of multimodal therapies. The aim of this review is to analyze the most commonly used TRG systems in gastrointestinal cancers highlighting their pitfalls and usefulness, depending on the tumor type.

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“…Similarly, AGR2 protein was significantly elevated in both serum and tissue samples of pharyngeal nasal cancers, and the increased levels were associated with tumor node metastasis and relapse along with the low survival rates of patients [63]. Likewise, in Barrett esophagus, the AGR2 expression was elevated in 125 AdC biopsy samples [64].…”

Section: Expression and Survivalmentioning

confidence: 99%

Leveraging the Role of the Metastatic Associated Protein Anterior Gradient Homologue 2 in Unfolded Protein Degradation: A Novel Therapeutic Biomarker for Cancer

Alsereihi

Schulten

Bakhashab

et al. 2019

Cancers

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Effective diagnostic, prognostic and therapeutic biomarkers can help in tracking disease progress, predict patients’ survival, and considerably affect the drive for successful clinical management. The present review aims to determine how the metastatic-linked protein anterior gradient homologue 2 (AGR2) operates to affect cancer progression, and to identify associated potential diagnostic, prognostic and therapeutic biomarkers, particularly in central nervous system (CNS) tumors. Studies that show a high expression level of AGR2, and associate the protein expression with the resilience to chemotherapeutic treatments or with poor cancer survival, are reported. The primary protein structures of the seven variants of AGR2, including their functional domains, are summarized. Based on experiments in various biological models, this review shows an orchestra of multiple molecules that regulate AGR2 expression, including a feedback loop with p53. The AGR2-associated molecular functions and pathways including genomic integrity, proliferation, apoptosis, angiogenesis, adhesion, migration, stemness, and inflammation, are detailed. In addition, the mechanisms that can enable the rampant oncogenic effects of AGR2 are clarified. The different strategies used to therapeutically target AGR2-positive cancer cells are evaluated in light of the current evidence. Moreover, novel associated pathways and clinically relevant deregulated genes in AGR2 high CNS tumors are identified using a meta-analysis approach.

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Anterior gradient 2 profiling in Barrett columnar epithelia and adenocarcinoma

Cited by 7 publications

References 39 publications

Quantitative Shotgun Proteomics Unveils Candidate Novel Esophageal Adenocarcinoma (EAC)-specific Proteins

Quantitative Shotgun Proteomics Unveils Candidate Novel Esophageal Adenocarcinoma (EAC)-specific Proteins

Pathological Tumor Regression Grade Classifications in Gastrointestinal Cancers: Role on Patients’ Prognosis

Leveraging the Role of the Metastatic Associated Protein Anterior Gradient Homologue 2 in Unfolded Protein Degradation: A Novel Therapeutic Biomarker for Cancer

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