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01.12.2018 | Research | Ausgabe 1/2018 Open Access

Journal of Translational Medicine 1/2018

Integrative analysis of the cancer genome atlas and cancer cell lines encyclopedia large-scale genomic databases: MUC4/MUC16/MUC20 signature is associated with poor survival in human carcinomas

Zeitschrift:
Journal of Translational Medicine > Ausgabe 1/2018
Autoren:
Nicolas Jonckheere, Isabelle Van Seuningen
Wichtige Hinweise

Electronic supplementary material

The online version of this article (https://​doi.​org/​10.​1186/​s12967-018-1632-2) contains supplementary material, which is available to authorized users.

Abstract

Background

MUC4 is a membrane-bound mucin that promotes carcinogenetic progression and is often proposed as a promising biomarker for various carcinomas. In this manuscript, we analyzed large scale genomic datasets in order to evaluate MUC4 expression, identify genes that are correlated with MUC4 and propose new signatures as a prognostic marker of epithelial cancers.

Methods

Using cBioportal or SurvExpress tools, we studied MUC4 expression in large-scale genomic public datasets of human cancer (the cancer genome atlas, TCGA) and cancer cell line encyclopedia (CCLE).

Results

We identified 187 co-expressed genes for which the expression is correlated with MUC4 expression. Gene ontology analysis showed they are notably involved in cell adhesion, cell–cell junctions, glycosylation and cell signaling. In addition, we showed that MUC4 expression is correlated with MUC16 and MUC20, two other membrane-bound mucins. We showed that MUC4 expression is associated with a poorer overall survival in TCGA cancers with different localizations including pancreatic cancer, bladder cancer, colon cancer, lung adenocarcinoma, lung squamous adenocarcinoma, skin cancer and stomach cancer. We showed that the combination of MUC4, MUC16 and MUC20 signature is associated with statistically significant reduced overall survival and increased hazard ratio in pancreatic, colon and stomach cancer.

Conclusions

Altogether, this study provides the link between (i) MUC4 expression and clinical outcome in cancer and (ii) MUC4 expression and correlated genes involved in cell adhesion, cell–cell junctions, glycosylation and cell signaling. We propose the MUC4/MUC16/MUC20high signature as a marker of poor prognostic for pancreatic, colon and stomach cancers.
Zusatzmaterial
Additional file 2: Figure S2. MUC4 expression in normal tissues. MUC4 expression was analyzed with https://​gtexportal.​org. Expression is shown as log10 of RKPM (read per kilobases of transcript per million map reads). Boxplot are shown as median and 25/75% percentile. Outliers are represented as points.
Additional file 7: Table S3. Hazard-ratio and survival analysis of top genes associated with MUC4 expression in TCGA tumor databases. Hazard ratio and p-value were determined using SurvExpress tool (https://​bioinformatica.​mty.​itesm.​mx/​SurvExpress). Risk groups were defined using the optimization algorithm (maximize) from the ordered prognostic. Selected genes (ADGRF1, LCN2, MUC20, C1ORF116, SCEL, STEAP4) harbored Pearson’s correlation with MUC4 > 0.5.
Literatur
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