HYALURONAN METABOLISM IS ASSOCIATED WITH DNA REPAIR GENES IN BREAST AND COLORECTAL CANCER.

CRISTINA, CAROLINA; VITALE, DAIANA L; SPINELLI, FIORELLA M.; ROMANO, LUCIA; GIANNONI, PAULA; SATURNO, VIRGINIA; CRISTINA, CAROLINA; ALANIZ, LAURA D.; SEVIC, INA

Congreso; Reunión conjunta SAIC - SAI - AAFE - NANOMED.AR; 2021

The tumor microenvironment (TME) plays an important role in the progression of cancer. One of its components that is frequently altered in tumors is Hyaluronan (HA) which has been associated with the aggressiveness of cancer. Also, it has been shown that changes in TME can lead to changes in the expression of BRCA1 and BRCA2 genes, which have been extensively studied in different tumors.Aim: The aim of this work was to compare mRNA levels of HA metabolism members and BRCA genes, between tumor (TT) and non-tumor adjacent tissue (NAT) in breast and colorectal cancer, and test its correlation with clinical biomarkers (ER, PR, HER2, KI67) and patient survival.Methods: We compared TT and NAT between HA metabolism members and the DNA repair genes by qPCR, and tested their correlation with biomarkers. We investigated relationship between mRNA expression and patient survival using the Kaplan?Meier Plotter database. The STRING analysis was used to evaluate a protein interaction networks between HA metabolism members and BRCA genes.Results: We show alteration in HA metabolism in colorectal but not breast cancer. We found a decrease in HYAL1 levels in breast but not colorectal cancer. We also show lower HA levels in TT compared with NAT. In both breast and colorectal cancer, CD44 and BRCA2 showed a strong positive correlation. Kaplan?Meier Plotter data showed that the mRNA expression levels of BRCA1 and 2 are higher in cancer than normal tissue and are significantly associated with the relapse-free survival (RFS). HYAL1 levels in breast cancer are higher in normal tissue but don?t influence survival. STRING analysis showed two clusters: HA metabolism (HAS2, HAS3, HYAL1, HYAL2, CD44) and DNA repair and regulation (BRCA1, BRCA2, TP53, EP300) with CD44 as a link between these processes.Conclusion: There is an association between HA metabolism and the DNA repair genes which gives us a new insight in the molecular mechanisms of the development and the progression of cancer.