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Proteomic and functional investigation of the colon cancer relapse-associated genes NOX4 and ITGA3.

ABSTRACT: Colon cancer is a major cause of cancer-related deaths worldwide. Adjuvant chemotherapy significantly reduces mortality in stage III colon cancer; however, it is only marginally effective in stage II patients. There is also increasing evidence that right-side colon cancer is different from left-side colon cancer. We have observed that the genes altered in expression between the poor and good prognosis tumors vary significantly depending on whether the malignancy originates on the right or left side of the colon. We have identified NADPH oxidase 4 (NOX4) to be highly predictive of relapse in stage II left-side colon cancer, whereas integrin alpha 3 beta 1 (ITGA3) is predictive of relapse in stage II right-side colon cancer. To investigate the underlying molecular mechanisms, we are analyzing the effect of ITGA3 and NOX4 silencing via RNA interference and pharmacological inhibition on global protein expression patterns via iTRAQ labeling and mass spectrometry in colon cancer cells. On the basis of bioinformatic analysis, the functions of these genes were assessed through phenotypic assays, revealing roles in cell migration and reactive oxygen species generation. These biomarkers for relapse risk are of clinical interest and lead to insight into how a tumor progresses to metastasis.

SUBMITTER: Bauer KM

PROVIDER: S-EPMC4227555 | biostudies-literature | 2014 Nov

REPOSITORIES: biostudies-literature

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Proteomic and functional investigation of the colon cancer relapse-associated genes NOX4 and ITGA3.

Bauer Kerry M KM Watts Tanya N TN Buechler Steven S Hummon Amanda B AB

Journal of proteome research 20140818 11

Colon cancer is a major cause of cancer-related deaths worldwide. Adjuvant chemotherapy significantly reduces mortality in stage III colon cancer; however, it is only marginally effective in stage II patients. There is also increasing evidence that right-side colon cancer is different from left-side colon cancer. We have observed that the genes altered in expression between the poor and good prognosis tumors vary significantly depending on whether the malignancy originates on the right or left s ...[more]

PMID: 25096929

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Project description:The present study aimed to identify the recurrence‑associated genes in colon cancer, which may provide theoretical evidence for the development of novel methods to prevent tumor recurrence. Colon cancer and matched normal samples microarray data (E‑GEOD‑39582) were downloaded from ArrayExpress. Genes with significant variation were identified, followed by the screening of differentially expressed genes (DEGs). Subsequently, the co‑expression network of DEGs was constructed using the weighted correlation network analysis (WGCNA) method, which was verified using the validation dataset. The significant modules associated with recurrence in the network were subsequently screened and verified in another independent dataset E‑GEOD‑33113. Function and pathway enrichment analyses were also conducted to determine the roles of selected genes. Survival analysis was performed to identify the association between these genes and survival. A total of 434 DEGs were identified in the colon samples, and stress‑associated endoplasmic reticulum protein family member 2 (SERP2) and long non‑coding RNA‑0219 (LINC0219) were determined to be the vital DEGs between all the three sub‑type groups with different clinical features. The brown module was identified to be the most significant module in the co‑expression network associated with the recurrence of colon cancer, which was verified in the E‑GEOD‑33113 dataset. Top 10 genes in the brown module, including EGF containing fibulin like extracellular matrix protein 2 (EFEMP2), fibrillin 1 (FBN1) and secreted protein acidic and cysteine rich (SPARC) were also associated with survival time of colon cancer patients. Further analysis revealed that the function of cell adhesion, biological adhesion, extracellular matrix (ECM) organization, pathways of ECM‑receptor interaction and focal adhesion were the significantly changed terms in colon cancer. In conclusion, SERP2, EFEMP2, FBN1, SPARC, and LINC0219 were revealed to be the recurrence‑associated molecular and prognostic indicators in colon cancer by WGCNA co‑expression network analysis.

Dataset Information

Proteomic and functional investigation of the colon cancer relapse-associated genes NOX4 and ITGA3.

Publications

Proteomic and functional investigation of the colon cancer relapse-associated genes NOX4 and ITGA3.

Similar Datasets

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