Quantitative Proteomic Studies On TNBC In Premenopausal And Postmenopausal Patients

Objective:Triple-negative breast cancer (TNBC) is a special kind of high-risk breast cancersubtypes, which is common in premenopausal young women. The feature of TNBC includesearly clinical relapse, high recurrence rate, poor treatment effect etc. In our study, through acomparative analysis of total protein differential expression profile in carcinoma andpara-carcinoma tissue of premenopausal and postmenopausal TNBC patients with theconditions of different hormone levels, the effect of menopause on TNBC is in-depthanalyzed to investigate the differences of mechanism for TNBC before and after menopauseand select potential therapeutic target.Methods:In this study, carcinoma and para-carcinoma tissue of premenopausal andpostmenopausal TNBC patients were used as research material. The carcinoma and para-carcinoma tissue of premenopausal and postmenopausal TNBC patients were mixed into thepool (pool) and divided into two groups. Total protein differential expressions of thecarcinoma and para-carcinoma tissue of premenopausal and postmenopausal TNBC patientswere analyzed, respectively, using the iTRAQ technology and methods of comparativeproteomics. Go analysis was used to obtain the changes of metabolic pathway difference. Onthis basis, the second comparative method of premenopausal and postmenopausal differentialproteins was used to investigate the effect of menopause on TNBC.Results:Study found that compared with para-carcinoma tissue, the amount of differential proteinin premenopausal carcinoma tissue was214in all, which existed in3significant differentialpathways. The amount of differential protein in postmenopausal carcinoma tissue was360,which existed in15differential pathways. The results indicated that under different estrogenenvironment, TNBC might have different mechanisms. The results of second comparativemethod of premenopausal and postmenopausal differential proteins showed thatpremenopausal differential expressive protein were FN1, LMAN1, DNAJA2, postmenopausal differential proteins were ILK, P4HB, SSR3and HSPA5. These proteins were considered asnew potential therapeutic targets of premenopausal or postmenopausal TNBC patients.Conclusion: In our study, the iTRAQ technology was used to analyze the total proteindifferential expression in carcinoma and para-carcinoma tissue of premenopausal andpostmenopausal TNBC patients, explore the effect of menopause on TNBC, which providesnew theoretical basis and data support for comprehensive analysis of TNBC pathogenesis.1. iTRAQ technology was used to analyze the proteome carcinoma and para-carcinomatissue of premenopausal and postmenopausal TNBC patients.The differentially expressedgenes were determined, and functional analysis of these genes was conducted to find thesignal transduction pathways involved by these proteins. The differential protein obtained byiTRAQ technique was not entirely consistent to that in reported studies, which indicated thatthe protein expression of TNBC had a certain particularity.2. Compared with para-carcinoma tissue, found that differential proteins inpostmenopausal carcinoma tissue were significantly more than that in premenopausalcarcinoma tissue. The differential significant pathways in two groups were also different,which indicated that under different estrogen environment, TNBC might have differentmechanisms.3. The results of second comparative method of premenopausal and postmenopausaldifferential proteins showed that there were3differential proteins expecial in premenopausaland4in postmenopausal, may be potential new therapeutic targets.