Prognostic implications of markers of the metabolic phenotype in human cutaneous melanoma

Abstract

Background

Reprogramming of energy metabolism to enhanced aerobic glycolysis has been defined as a hallmark of cancer.

Objective

To investigate the role of the mitochondrial proteins, β‐subunit of the H⁺‐ATP synthase (β‐F1‐ATPase), and heat‐shock protein 60 (HSP60), and the glycolytic markers, glyceraldehyde‐3‐phosphate dehydrogenase (GAPDH) and pyruvate kinase M2 (PKM2), as well as the bioenergetic cellular (BEC) index, in melanoma progression.

Material and Methods

The expression of energy metabolism proteins were assessed on a set of different melanoma cells representing the natural biological history of the disease: primary cultures of melanocytes, radial (WM35) and vertical (WM278) growth phases, and poorly (C81‐61‐PA) and highly (C8161‐HA) aggressive melanoma cells. Cohorts of 63 melanocytic nevi, 55 primary melanomas and 35 metastases were used; and 108 primary melanoma and 30 metastases were used for validation.

Results

The BEC index was significantly reduced in melanoma cells and correlated with their aggressive characteristics. Overexpression of HSP60, GAPDH and PKM2 was detected in melanoma human samples compared with nevi, showing a gradient of increased expression from radial growth phase to metastatic melanoma. The BEC index was also significantly reduced in melanoma samples and correlated with worse overall and disease‐free survival; the multivariate Cox analysis showed that BEC index (HR, 0.64; CI95%, 0.4‐1.2) is an independent predictor for overall survival.

Conclusion

A profound alteration in the mitochondrial and glycolytic proteins and in the BEC index occurs in the progression of melanoma, which correlates with worse outcome supporting that the alteration of the metabolic phenotype is crucial in melanoma transformation.

This article is protected by copyright. All rights reserved.

https://ift.tt/2rtyFdP