Dataset Information

Proteomic Features of Colorectal Cancer Identify Tumor Subtypes Independent of Oncogenic Mutations and Independently Predict Relapse-Free Survival.

ABSTRACT:

Background

The directed study of the functional proteome in colorectal cancer (CRC) has identified critical protein markers and signaling pathways; however, the prognostic relevance of many of these proteins remains unclear.

Methods

We determined the prognostic implications of the functional proteome in 263 CRC tumor samples from patients treated at MD Anderson Cancer Center (MDACC) and 462 patients from The Cancer Genome Atlas (TCGA) to identify patterns of protein expression that drive tumorigenesis. A total of 163 validated proteins were analyzed by reverse phase protein array (RPPA). Unsupervised hierarchical clustering of the tumor proteins from the MDACC cohort was performed, and clustering was validated using RPPA data from TCGA CRC. Cox regression was used to identify predictors of tumor recurrence.

Results

Clustering revealed dichotomization, with subtype A notable for a high epithelial-mesenchymal transition (EMT) protein signature, while subtype B was notable for high Akt/TSC/mTOR pathway components. Survival data were only available for the MDACC cohort and were used to evaluate prognostic relevance of these protein signatures. Group B demonstrated worse relapse-free survival (hazard ratio 2.11, 95% confidence interval 1.04-4.27, p = 0.039), although there was no difference in known genomic drivers between the two proteomic groups. Proteomic grouping and stage were significant predictors of recurrence on multivariate analysis. Eight proteins were found to be significant predictors of tumor recurrence on multivariate analysis: Collagen VI, FOXO3a, INPP4B, LcK, phospho-PEA15, phospho-PRAS40, Rad51, phospho-S6.

Conclusion

CRC can be classified into distinct subtypes by proteomic features independent of common oncogenic driver mutations. Proteomic analysis has identified key biomarkers with prognostic importance, however these findings require further validation in an independent cohort.

SUBMITTER: Clarke CN

PROVIDER: S-EPMC6063735 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature

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Publications

Proteomic Features of Colorectal Cancer Identify Tumor Subtypes Independent of Oncogenic Mutations and Independently Predict Relapse-Free Survival.

Clarke Callisia N CN Lee Michael S MS Wei Wei W Manyam Ganiraju G Jiang Zhi-Qin ZQ Lu Yiling Y Morris Jeffrey J Broom Bradley B Menter David D Vilar-Sanchez Eduardo E Raghav Kanwal K Eng Cathy C Chang George J GJ Simon Iris I Bernards Rene R Overman Michael M Mills Gordon B GB Maru Dipen D Kopetz Scott S

Annals of surgical oncology 20170921 13

<h4>Background</h4>The directed study of the functional proteome in colorectal cancer (CRC) has identified critical protein markers and signaling pathways; however, the prognostic relevance of many of these proteins remains unclear.<h4>Methods</h4>We determined the prognostic implications of the functional proteome in 263 CRC tumor samples from patients treated at MD Anderson Cancer Center (MDACC) and 462 patients from The Cancer Genome Atlas (TCGA) to identify patterns of protein expression tha ...[more]

PMID: 28936799

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Project description:Background: Perturbation of energy metabolism exacerbates cardiac dysfunction, serving as a potential therapeutic target in congestive heart failure. Although circulating free fatty acids (FFAs) are linked to insulin resistance and risk of coronary heart disease, it still remains unclear whether circulating FFAs are associated with the prognosis of patients with acute heart failure (AHF). Methods: This single-center, observational cohort study enrolled 183 AHF patients (de novo heart failure or decompensated chronic heart failure) in the Second Affiliated Hospital, Zhejiang University School of Medicine. All-cause mortality and heart failure (HF) rehospitalization within 1 year after discharge were investigated. Serum FFAs were modeled as quartiles as well as a continuous variable (per SD of FFAs). The restricted cubic splines and cox proportional hazards models were applied to evaluate the association between the serum FFAs level and all-cause mortality or HF rehospitalization. Results: During a 1-year follow-up, a total of 71 (38.8%) patients had all-cause mortality or HF rehospitalization. The levels of serum FFAs positively contributed to the risk of death or HF rehospitalization, which was not associated with the status of insulin resistance. When modeled with restricted cubic splines, the serum FFAs increased linearly for the incidence of death or HF rehospitalization. In a multivariable analysis adjusting for sex, age, body-mass index, coronary artery disease, diabetes mellitus, hypertension, left ventricular ejection fraction and N-terminal pro-brain natriuretic peptid, each SD (303.07 μmol/L) higher FFAs were associated with 26% higher risk of death or HF rehospitalization (95% confidence interval, 2-55%). Each increasing quartile of FFAs was associated with differentially elevated hazard ratios for death or HF rehospitalization of 1 (reference), 1.71 (95% confidence interval, [0.81, 3.62]), 1.41 (95% confidence interval, [0.64, 3.09]), and 3.18 (95% confidence interval, [1.53, 6.63]), respectively. Conclusion: Serum FFA levels at admission among patients with AHF were associated with an increased risk of adverse outcomes. Additional studies are needed to determine the causal-effect relationship between FFAs and acute cardiac dysfunction and whether FFAs could be a potential target for AHF management.

Dataset Information

Proteomic Features of Colorectal Cancer Identify Tumor Subtypes Independent of Oncogenic Mutations and Independently Predict Relapse-Free Survival.

Background

Methods

Results

Conclusion

Publications

Proteomic Features of Colorectal Cancer Identify Tumor Subtypes Independent of Oncogenic Mutations and Independently Predict Relapse-Free Survival.

Similar Datasets

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