Detection of hyaluronan and mutations in sputum liquid biopsy as screening in patient with lung cancer

• Grant number: 15/26642-4
• Support type: Research Grants - Young Investigators Grants
• Duration: July 01, 2017 - June 30, 2021
• Field of knowledge: Health Sciences - Medicine
• Principal Investigator: Vanessa Karen de Sá
• Grantee: Vanessa Karen de Sá
• Home Institution: A C Camargo Cancer Center. Fundação Antonio Prudente (FAP). São Paulo , SP, Brazil
• Associated scholarship(s): 19/09910-6 - Identification of mutations in EGFR, KRAS, BRAF and NRAS genes in sputum biopsy and its correlation with tumor specimens in patients with NSCLC, BP.MS; 18/19545-0 - Validation of hyaluronic acid as a biomarker diagnosis and prediction in sputum of patients with lung carcinoma, BP.MS; 17/14590-5 - Detection of hyaluronan and mutations in sputum liquid biopsy as screening in patient with lung cancer, BP.JP

Abstract

In Brazil, estimates of incidence and mortality in 2016 from National Cancer Institute (INCA) show that this neoplasm should reach 28,220 people, including 17,330 males 10,890 females. There is an urgency to develop new noninvasive diagnostic methods for greater comfort and less patient anxiety. Amid this scenario, several research groups have invested deeply in the search for biomarkers in the development of new techniques that can assist in the diagnosis, prognosis and treatment of lung cancer (LC). Currently, the researchers focus is on liquid biopsies represented by blood, sputum or bronchial washings for the early detection of lung cancer. However, to date no research group has succeeded in standardizing these markers for widespread use in clinical practice. Intracellular proteins and extracellular matrix (ECM) have been shown to be potential diagnostic markers present in secretions, especially in the blood, saliva, sputum and urine.Initially, we demonstrated direct and significant association between tumors with high percentage of HA and microvessel density (MVD) and the potential for malignancy. Equally significant was the direct association between metastatic tumors high HA levels in cancer cells. Cox regression showed lower risk of death for patients with low HA levels in tissue. Interestingly, increased levels of HA were detected in sputum of patients with lung cancer compared to healthy volunteers, as well as a significant correlation between the HA levels in sputum and tumor tissue.Finally, the emergence of new sequencing platforms at a lower cost, lack of biopsy material - inherent in most patients with lung cancer - the need for rapid results to support both subsequent treatment lines, the inclusion of patients clinical trials with new drug target, points to the increased use of molecular tests in liquid biopsies allowing the simultaneous analysis of multiple mutations drivers.As young researcher, our proposal is to continue the study on validating new cohort that expression of HA and gene mutations in tissue can reflect up sputum, emerging as tool for the early detection of lung cancer. (AU)