Abstract
Recently, the Cancer Genome Atlas and Asian Cancer Research Group propose two new classifications system of gastric cancer by using multi-platforms of molecular analyses. However, these highly complicated and cost technologies have not yet been translated into full clinical utility. In addition, the clinicians are expected to gain more guidance of treatment for different molecular subtypes. In this study, we developed a panel of gastric cancer patients in population from Southern China using commercially accessible TMA and immunohistochemical technology. A cohort of 259 GC patients was classified into 4 subtypes on the basis of expression of mismatch repair proteins (PMS2, MLH1, MSH2, and MSH6), E-cadherin and p21 protein. We observed that the subtypes presented distinct prognosis. dMMR-like subtype was associated with the best prognosis, and E-cadherin-a subtype was associated with the worst prognosis. Patients with p21-High and p21-Ligh subtypes had intermediate overall survival. In multivariate analysis, the dMMR-like subtype remained an independent prediction power for overall survival in the model. We described a molecular classification of gastric cancers using clinically applicable assay. The biological relevance of the four subtypes was illustrated by significant differences in prognosis. Our molecular classification provided an effective and inexpensive screening tool for improving prognostic models. Nevertheless, our study should be considered preliminary and carries a limited predictive value as a single-center retrospective study.
Highlights
Gastric cancer (GC) is the third-leading cause of cancer-related mortality worldwide [1, 2], and more than half of those cases occur in eastern Asian countries [3, 4]
137 cases (52.9%) were in stages III according to the 7th edition of the TNM classification by American Joint Committee on Cancer (AJCC) [19]. 136 patients received adjuvant chemotherapy and all regimens were almost based on oxaliplatin after surgery
Under the guidance and inspiration of Asian Cancer Research Group (ACRG) studies [12], we chose several potential biomarkers as follows: Mismatch-repair deficiency like phenotype represented a hallmark feature of microsatellite instability (MSI) status [25, 26]; aberrant expression of E-cadherin (E-cadherin-a) was related to epithelial-to-mesenchymal transition (EMT) phenotype [27]; low expression of p21 (p21-Low) was somehow linked to p53 inactivation and high expression of p21 (p21-High) to p53 activation, and a molecular classification of GC can be established based on hierarchical cluster analysis of the protein profiles
Summary
Gastric cancer (GC) is the third-leading cause of cancer-related mortality worldwide [1, 2], and more than half of those cases occur in eastern Asian countries [3, 4].
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