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PSMB8 and PBK as potential gastric cancer subtype-specific biomarkers associated with prognosis.

ABSTRACT: Gastric adenocarcinoma is a common form of cancer associated with a poor prognosis. We analyzed microarray profiling data from 48 patients with gastric adenocarcinoma to characterize gastric cancer subtypes and identify biomarkers associated with prognosis. We identified two major subtypes of gastric adenocarcinoma differentially associated with overall survival (P = 0.025). Genes that were differentially expressed were identified using specific criteria (P < 0.001 and >1.5-fold); expression of 294 and 116 genes was enriched in good and poor prognosis subtypes, respectively. Genes related to translational elongation and cell cycle were upregulated in the poor prognosis group. Of these genes, upregulation of proteasome subunit beta type 8 PSMB8 and PDZ binding kinase PBK was confirmed by real-time reverse transcription-PCR analysis. PSMB8 or PBK knockdown had no effect on gastric cancer cell proliferation but suppressed cell migration and invasion, respectively. Furthermore, immunohistochemistry analysis of 385 gastric cancer patients revealed that increased nuclear expression of PSMB8 and PBK was correlated with depth of invasion, lymph node metastasis, and lower survival rates. Taken together, two gastric adenocarcinoma subtypes were predictive of prognosis. PSMB8 and PBK were predictive of gastric cancer prognosis and could be potential gastric cancer subtype-specific biomarkers.

SUBMITTER: Kwon CH

PROVIDER: S-EPMC5008298 | biostudies-literature | 2016 Apr

REPOSITORIES: biostudies-literature

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PSMB8 and PBK as potential gastric cancer subtype-specific biomarkers associated with prognosis.

Kwon Chae Hwa CH Park Hye Ji HJ Choi Yu Ri YR Kim Ahrong A Kim Hye Won HW Choi Jin Hwa JH Hwang Chung Su CS Lee So Jung SJ Choi Chang In CI Jeon Tae Yong TY Kim Dae Hwan DH Kim Gwang Ha GH Park Do Youn do Y

Oncotarget 20160401 16

Gastric adenocarcinoma is a common form of cancer associated with a poor prognosis. We analyzed microarray profiling data from 48 patients with gastric adenocarcinoma to characterize gastric cancer subtypes and identify biomarkers associated with prognosis. We identified two major subtypes of gastric adenocarcinoma differentially associated with overall survival (P = 0.025). Genes that were differentially expressed were identified using specific criteria (P < 0.001 and >1.5-fold); expression of ...[more]

PMID: 26894977

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Project description:ObjectiveThe aim of this study was to identify the expression of miRNA and lymphocyte subsets in the blood of gastric cancer (GC) patients, elucidate their clinical significance in GC, and establish novel biomarkers for the early diagnosis and prognosis of GC.MethodsThe expression of miRNAs in the serum of GC patients was screened using second-generation sequencing and detected using qRT-PCR. The correlation between miRNA expression and clinicopathological characteristics of GC patients was analyzed, and molecular markers for predicting cancer were identified. Additionally, flow cytometry was used to detect the proportion of lymphocyte subsets in GC patients compared to healthy individuals. The correlations between differential lymphocyte subsets, clinicopathological features of GC patients, and their prognosis were analyzed statistically.ResultsThe study revealed that hsa-miR-1306-5p, hsa-miR-3173-5p, and hsa-miR-296-5p were expressed at lower levels in the blood of GC patients, which is consistent with miRNA-seq findings. The AUC values of hsa-miR-1306-5p, hsa-miR-3173-5p, and hsa-miR-296-5p were found to be effective predictors of GC occurrence. Additionally, hsa-miR-296-5p was found to be negatively correlated with CA724. Furthermore, hsa-miR-1306-5p, hsa-miR-3173-5p, and hsa-miR-296-5p were found to be associated with the stage of the disease and were closely linked to the clinical pathology of GC. The lower the levels of these miRNAs, the greater the clinical stage of the tumor and the worse the prognosis of gastric cancer patients. Finally, the study found that patients with GC had lower absolute numbers of CD3+ T cells, CD4+ T cells, CD8+ T cells, CD19+ B cells, and lymphocytes compared to healthy individuals. The quantity of CD4+ T lymphocytes and the level of the tumor marker CEA were shown to be negatively correlated. The ROC curve and multivariate logistic regression analysis demonstrated that lymphocyte subsets can effectively predict gastric carcinogenesis and prognosis.ConclusionThese miRNAs such as hsa-miR-1306-5p, hsa-miR-3173-5p, hsa-miR-296-5p and lymphocyte subsets such as the absolute numbers of CD3+ T cells, CD4+ T cells, CD8+ T cells, CD19+ B cells, lymphocytes are down-regulated in GC and are closely related to the clinicopathological characteristics and prognosis of GC patients. They may serve as new molecular markers for predicting the early diagnosis and prognosis of GC patients.

Dataset Information

PSMB8 and PBK as potential gastric cancer subtype-specific biomarkers associated with prognosis.

Publications

PSMB8 and PBK as potential gastric cancer subtype-specific biomarkers associated with prognosis.

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