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Transcriptome profiling of cancer tissues in Chinese patients with gastric cancer by high-throughput sequencing.

ABSTRACT: Gastric cancer (GC) is the fifth most common malignancy and the third leading cause of cancer-associated mortality worldwide. Therefore, there is a requirement to identify sufficiently sensitive biomarkers for GC. Genome-wide screening of transcriptome dysregulation among cancerous and normal tissues may provide insights into the underlying molecular mechanisms of GC initiation and progression. At present, high-throughput sequencing techniques have begun to innovate biomedical studies. The RNA-seq method has become an advanced approach in medical studies; it is capable of the accurate detection of gene expression levels. The present study used RNA-seq to evaluate the transcriptional changes between tumor and matched normal samples, and these changes were confirmed by differentially expressed genes in larger samples using the results of sequencing. In total, the upregulation of 28 mRNAs and downregulation of 22 mRNAs between cancerous and normal tissue samples were identified. Subsequently, five differentially expressed genes were selected to verify in large samples and cadherin-1 (CDH1) was selected to detect protein expression levels. The results revealed that CDH1, cyclooxygenase-2 and matrix metalloproteinase genes had significantly higher expression levels, whereas the expression levels of dermatopontin and transforming growth factor ? receptor 2 were decreased in GC samples. In particular, CDH1 demonstrated a 36-fold higher expression level in cancer tissues. The western blotting results also revealed high CDH1 expression levels in the validation cohorts. Furthermore, these genes are highly enriched in certain gene ontology categories, including the digestive system process, secretion and digestion. The present study provided a preliminary survey of the transcriptome of Chinese patients with GC, which may improve the detection of aberrant gene expression in GC and the understanding of the mechanisms of tumorigenesis.

SUBMITTER: Tian P

PROVIDER: S-EPMC5777123 | biostudies-literature | 2018 Feb

REPOSITORIES: biostudies-literature

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Transcriptome profiling of cancer tissues in Chinese patients with gastric cancer by high-throughput sequencing.

Tian Peiying P Liang Chunli C

Oncology letters 20171208 2

Gastric cancer (GC) is the fifth most common malignancy and the third leading cause of cancer-associated mortality worldwide. Therefore, there is a requirement to identify sufficiently sensitive biomarkers for GC. Genome-wide screening of transcriptome dysregulation among cancerous and normal tissues may provide insights into the underlying molecular mechanisms of GC initiation and progression. At present, high-throughput sequencing techniques have begun to innovate biomedical studies. The RNA-s ...[more]

PMID: 29434905

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Project description:Gastric cancer is the fourth most common cause of cancer-related death. Currently, it is broadly accepted that the molecular complexity and heterogeneity of gastric cancer, both inter- and intra-tumor, display important barriers for finding specific biomarkers for the early detection and diagnosis of this malignancy. Early-onset gastric cancer is not as prevalent as conventional gastric carcinoma, but it is a preferable model for studying the genetic background, as young patients are less exposed to environmental factors, which influence cancer development. The main objective of this study was to reveal age-dependent genotypic characteristics of gastric cancer subtypes, as well as conduct mutation profiling for the most frequent alterations in gastric cancer development, using targeted next-generation sequencing technology. The study group included 53 patients, consisting of 18 patients with conventional gastric cancer and 35 with an early-onset subtype. The DNA of all index cases was used for next-generation sequencing, employing a panel of 94 genes and 284 single nucleotide polymorphisms (SNPs) (TruSight Cancer Panel, Illumina), which is characteristic for common and rare types of cancer. From among the 53 samples processed for sequencing, we were able to identify seven candidate genes (STK11, RET, FANCM, SLX4, WRN, MEN1, and KIT) and nine variants among them: one splice_acceptor, four synonymous, and four missense variants. These were selected for the age-dependent differentiation of gastric cancer subtypes. We found four variants with C-Score ≥ 10, as 10% of the most deleterious substitutions: rs1800862 (RET), rs10138997 (FANCM), rs2230009 (WRN), and rs2959656 (MEN1). We identified 36 different variants, among 24 different genes, which were the most frequent genetic alterations among study subjects. We found 16 different variants among the genes that were present in 100% of the total cohort: SDHB (rs2746462), ALK (rs1670283), XPC (rs2958057), RECQL4 (rs4925828; rs11342077, rs398010167; rs2721190), DDB2 (rs326212), MEN1 (rs540012), AIP (rs4930199), ATM (rs659243), HNF1A (rs1169305), BRCA2 (rs206075; rs169547), ERCC5 (rs9514066; rs9514067), and FANCI (rs7183618). The technology of next-generation sequencing is a useful tool for studying the development and progression of gastric carcinoma in a high-throughput way. Our study revealed that early-onset gastric cancer has a different mutation frequency profile in certain genes compared to conventional subtype.

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Dataset Information

Transcriptome profiling of cancer tissues in Chinese patients with gastric cancer by high-throughput sequencing.

Publications

Transcriptome profiling of cancer tissues in Chinese patients with gastric cancer by high-throughput sequencing.

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