Abstract
Gastric cardia adenocarcinoma (GCA), which occurs at the gastroesophageal boundary, is one of the most malignant types of cancer. Over the past 30 years, the incidence of GCA has increased by approximately sevenfold, which has a more substantial increase than that of many other malignancies. However, as previous studies mainly focus on non-cardia gastric cancer, until now, the mechanisms behind GCA remain largely unknown. MicroRNAs (miRNAs) have been shown to play pivotal roles in carcinogenesis. To gain insight into the molecular mechanisms regulated by miRNAs in GCA development, we investigated miRNA expression profiles using 81 pairs of primary GCAs and corresponding non-tumorigenic tissues. First, 21 pairs of samples were used for microarray analysis, and then another 60 pairs of samples were used for further analysis. Our results showed that 464 miRNAs (237 upregulated, 227 downregulated, false discovery rate FDR <0.05) were differently expressed between GCA and non-tumor tissues. Pearson test and pathway analysis revealed that these dysregulated miRNA correlated coding RNAs may have effects on several cancer-related pathways. Four miRNAs (miR-1244, miR-135b-5p, miR-3196, and miR-628-3p) were found to be associated with GCA differentiation. One miRNA, miR-196a-5p, was found to be associated with age of GCA onset. Further, survival analysis showed that the expression level of miR-135b-5p was associated with GCA survival. Taken together, our study first provided the genome-wide expression profiles of miRNA in GCA and will be good help for further functional studies.
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Acknowledgments
This work was supported by the Natural Science Foundation of China (NSFC, 81472234, GSG).
The authors would like to thank Professor LemingShi (Center for Pharmacogenomics, State Key Laboratory of Genetic Engineering and MOE Key Laboratory of Contemporary Anthropology, Schools of Life Sciences and Pharmacy, Fudan University, Shanghai 201203, China) for data analysis.
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Shegan Gao, Fuyou Zhou and Chen Zhao contributed equally to this work.
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Table S1
Significantly down- and up-regulated miRNAs. (DOC 400 kb)
Supplementary Fig S1
Validation of EIF2 pathway and mTOR pathway. A, fold change of four important genes in EIF2 pathway (tumor/normal); B, fold change of four important genes in mTOR pathway (tumor/normal). (TIF 125 kb)
Supplementary Fig. S2
Examples of well (A), medium (B), and poor (C)differentiation GCA samples (200×). (TIF 5291 kb)
ESM 1
(TIF 5931 kb)
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Gao, S., Zhou, F., Zhao, C. et al. Gastric cardia adenocarcinoma microRNA profiling in Chinese patients. Tumor Biol. 37, 9411–9422 (2016). https://doi.org/10.1007/s13277-016-4824-5
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DOI: https://doi.org/10.1007/s13277-016-4824-5