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Integrated analysis identified an intestinal-like and a diffuse-like gene sets that predict gastric cancer outcome

  • Original Article
  • Published:
Tumor Biology

Abstract

The two major histological types of gastric cancer, intestinal and diffuse subtypes, have distinct epidemiological and pathophysiological features and were also suggested to be of diverse clinical outcomes. Although the gene expression spectrum of gastric cancer subtypes has been reported by previous studies, its linkage with gastric cancer clinical features and outcomes remains elusive. We investigated large-sample online gastric cancer datasets for seeking genes correlated with the clinical diversities between gastric cancer intestinal and diffuse subtypes. Genes differently expressed between the two subtypes were assessed by multiple statistical analysis and were testified on cellular level by quantitative RT-PCR. Related genes were combined to generate a risk signature, and their mutual linkages were also explored. Among genes overexpressed in intestinal subtype, ATPIF1, PRDX2, PRKAR2A, and SMC1A were correlated with positive prognosis. Among genes overexpressed in diffuse subtype, DTNA, GPR161, IDS, RHOQ, and TSHZ2 were correlated with negative prognosis. These nine genes were all novel independent prognostic factors. When used in combination as signatures, these two gene sets displayed strong efficacy for prediction of the prognosis and clinical variables in gastric and colorectal cancer. Hence, these two genes sets were respectively defined as the favorable intestinal-like and adverse diffuse-like gene sets. We identified nine novel genes correlated with the clinical diversity between the intestinal and diffuse subtypes of gastric cancer. The malignant changes from the intestinal to diffuse subtype might be due to the reduction of the four intestinal-like genes, as well as the elevation of the five diffuse-like genes.

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Acknowledgments

We deeply appreciate Jing Yan for the kind provision of specimens and helpful suggestions on experimental design. This study was supported by the National 973 Program of China (2015CB553906).

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Authors and Affiliations

  1. Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Biochemistry and Molecular Biology, Peking University Cancer Hospital and Institute, 52 Fucheng Road, Beijing, 100142, China

    Cheng Zhang, Li Min, Jiafei Liu, Like Qu & Chengchao Shou

  2. Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Division of Cancer Etiology, Peking University Cancer Hospital & Institute, Beijing, 100142, China

    Wei Tian

  3. Department of Pathology, Zhejiang Provincial People’s Hospital, Zhejiang, 310014, China

    Yong Han

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  1. Cheng Zhang
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  2. Li Min
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Correspondence to Chengchao Shou.

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The experiments described in the manuscript comply with the current laws of the countries in which they were performed.

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Electronic supplementary material

Table S1

Comparison of the expression values of 4 intestinal- and 5 diffuse-like genes in all three gastric cancer datasets (student’s t test, p < 0.05 was considered significant). (DOCX 19 kb)

Table S2

Primer sequences for quantitative real-time PCR (DOCX 12 kb)

Fig. S1

Subtype-related genes’ relationship with gastric cancer patient survival and disease-free survival were assessed by ROC analysis. Predictive values of intestinal-like genes during follow-up in training and validating datasets were shown as (a and c), while predictive values of diffuse-like genes during follow-up in training and validating datasets were shown as (b and d) (SPSS 17.0). AUC area under curve (JPEG 112 kb)

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Zhang, C., Min, L., Liu, J. et al. Integrated analysis identified an intestinal-like and a diffuse-like gene sets that predict gastric cancer outcome. Tumor Biol. 37, 16317–16335 (2016). https://doi.org/10.1007/s13277-016-5454-7

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