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Prognostic implication of TSC1 and mTOR expression in gastric carcinoma
Author(s) -
Byeon Sunju,
Han Nayoung,
Choi Jiwoon,
Kim Min A,
Kim Woo Ho
Publication year - 2014
Publication title -
journal of surgical oncology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.201
H-Index - 111
eISSN - 1096-9098
pISSN - 0022-4790
DOI - 10.1002/jso.23585
Subject(s) - tsc1 , pi3k/akt/mtor pathway , medicine , cancer , cancer research , immunohistochemistry , targeted therapy , oncology , carcinogenesis , biology , apoptosis , biochemistry
Background Gastric adenocarcinoma is the sixth most common and third most lethal cancer in the world. Except for HER2‐targeted therapy, targeted agents against specific molecules participating in gastric carcinogenesis, including those in the mechanistic target of rapamycin (serine/threonine kinase) (mTOR) pathway have not been proved to be effective. However, some studies have suggested that dysfunction of TSC1 may augment mTOR inhibitor activity. Methods We studied p‐mTOR and TSC1 status by immunohistochemical analysis of gastric carcinoma samples using a tissue microarray method and expression values adopted from The Cancer Genome Atlas. Results High p‐mTOR and low TSC1 expression status is associated with adverse clinicopathologic parameters. Patients with high p‐mTOR levels showed poor survival. Patients with low TSC1 levels showed unfavorable survival status in the overall patients group. The combination of p‐mTOR status and TSC1 status provided more strong survival information than using each parameter alone. Conclusions In gastric cancer, high p‐mTOR expression level is a statistically significant parameter in multivariate and Kaplan–Meier analyses (log‐rank test). In addition to p‐mTOR, TSC1 expression provided additional information to predict survival. We therefore suggest that evaluation of both p‐mTOR and TSC1 status may be helpful in clinical trials related to mTOR inhibitors. J. Surg. Oncol. 2014 109:812–817 . © 2014 Wiley Periodicals, Inc.