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Contribution of the integrative pathology to the discovery of biomarkers for non-small cell lung cancer : integrative pathology and lung cancer

Abstract : The non-small cell lung cancer (NSCLC) is the leading cause of cancer deaths in the world. Reliable and validated biomarkers could represent a possible breakthrough in the management of this tumour type, by facilitating diagnosis, refining prognosis and providing guidance towards the choice of the most appropriate therapy. In this thesis we approach the field of NSCLC biomarkers by exploring several aspects related to carcinogenesis and tumour progression. First, we have demonstrated a dual impact of two proteins activated by hypoxia, carbonic anhydrases IX and XII, on the outcome of NSCLC patients. We have demonstrated that high tissue and plasma CAIX expression may be a biomarker of poor prognosis and early relapse in NSCLC patients, whereas the CAXII tissue expression would be predictive of a favourable evolution. In addition, we have shown that dynamic reoxygenation of tumours would be at the origin of this antagonism. Furthermore, the cellular component of the tumour microenvironment has been studied and more particularly we have demonstrated that recruitment by the tumour cells of a subpopulation of neutrophils expressing a specific marker CD66b could have a positive signal during tumour progression of NSCLC. Thirdly, the blood compartment has been evaluated in relationship with the evolution of tumours and in particular we have demonstrated the major diagnostic and prognostic value of circulating tumour cells (CTCs) in patients with NSCLC. Finally, the CTC seem to represent the ideal tool for the detection of biomarkers theranostic in the NCPC. In conclusions, the works presented in this thesis explore possibilities and limitations of biomarker research in NSCLC, highlighting the importance of the quality of the samples and of the accuracy and completeness of clinical data in order to obtain reproducible results.
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Submitted on : Friday, October 18, 2013 - 9:28:11 AM
Last modification on : Monday, October 12, 2020 - 10:50:03 AM
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  • HAL Id : tel-00874504, version 1

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Marius Ionut Ilie. Contribution of the integrative pathology to the discovery of biomarkers for non-small cell lung cancer : integrative pathology and lung cancer. Agricultural sciences. Université Nice Sophia Antipolis, 2013. English. ⟨NNT : 2013NICE4042⟩. ⟨tel-00874504⟩

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