Skin carcinomas are the most frequent cancers in the world, including basal cell carcinomas and cutaneous squamous cell carcinoma (cSCCs), with more than 60.000 new annual cases in France. Their incidence increases mainly due to ultraviolet (UV) exposure and population ageing. Then from 1994 to 2006, the incidence of cSCC has increased by 300%. CSCCs typically manifests as a spectrum from a precursor actinic keratosis (AK) - possible spontaneous regression at this stage- to in situ cSCC invasive cSCC and finally metastatic cSCC.
Although growing evidence indicates that bioenergetic metabolism plays an important role in the progression of tumorigenesis, little information is available on the contribution of reprogramming of energy metabolism in cancer initiation and how it influences further the bioenergetic behavior of tumors. By applying a quantitative proteomic approach, the consortium has recently found that specific metabolic modifications precede cSCC. This study will investigate the role of energy metabolism in malignant transformation of premalignant skin lesions into cSCC, and in cSCC progression, with correlation with clinical characteristics and metastatic outcomes. Using several cutting-edge technologies in human samples, the team will evaluate whether targeting energy metabolism has the potential to be used as curative treatments for cSCC and whether pre-determined metabolic alterations could be exploited as new preventive strategies. These modifications in energy metabolism could be used as prognostic and diagnostic biomarkers.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
DIAGNOSTIC
Masking
NONE
Enrollment
200
Skin biopsies will be performed according to standard practices in the usual aseptic conditions, the operator wearing sterile gloves. A circular knife 3 mm will be used. Procedure interventions do not involve a drug or a device.
Hôpital Saint-André - CHU de Bordeaux
Bordeaux, France
RECRUITINGProportion of patients who have a glycolysis profile (proteomic analysis liquid chromatography-mass spectrometry (LC-MS/MS))
Metabolic profiling of different stages of carcinogenesis: glycolysis, oxidative phosphorylation
Time frame: Day 1
Proportion of patients who have an oxidative profile (proteomic analysis liquid chromatography-mass spectrometry (LC-MS/MS))
Metabolic profiling of different stages of carcinogenesis: glycolysis, oxidative phosphorylation
Time frame: Day 1
Evaluation of skin differentiation markers
% of samples in each category (AK, in situ, ...) that present differentiation features are assessed by immunostaining of loricrin, filaggrin, K10
Time frame: Day 1
Evaluation of cSCC aggressiveness markers
% of samples expressing aggressive markers will be assessed by evaluating the proliferation index, degree of differentiation, invasion beyond subcutaneous fat, perineural invasion, vascular invasion level of infiltration following immunohistochemistry analyses on formalin-fixed paraffin-embedded tissue sections.
Time frame: Day 1
Evaluation of skin apoptotic markers
% of samples with high apoptotic cell death level will be assessed by immunostaining using antibody against cleaved caspase-3.
Time frame: Day 1
Evaluation of mitochondrial metabolism on skin biopsies
% of samples with high mitochondrial activity will be evaluated by comparing oxygen consumption rate by different fresh samples.
Time frame: Day 1
Evaluation of cancer proliferative features on skin biopsies
% of samples that are highly proliferative will be calculated by measuring the ability of colony formation (SRB Test) and cell cycle progression (flow cytometer, western).
Time frame: Day 1
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