PO-487 Prognosis of triple negative breast cancer is associated with MHC II genes

• Published in: ESMO open Vol. 3; no. Suppl 2; pp. A420 - A421
• Main Authors: Li, Y, Zhao, A, Bond, GB, Varley, K, Forero, A, Lobuglio, A
• Format: Journal Article
• Language: English
• Published: Elsevier Ltd 01-07-2018
• ISSN: 2059-7029; 2059-7029
• DOI: 10.1136/esmoopen-2018-EACR25.989

IntroductionTriple negative breast cancer (TNBC) is clinically to denote women with invasive breast cancer whose tumours lack expression of oestrogen receptor (ER-), progesterone receptor (PR-), or overexpression of HER2/Neu. TNB tumours behave aggressively and are not candidates for ER or HER2/Neu targeted therapy. In previous published study of 47 TNBC patients with RNA-seq data, we discovered that twenty-four genes related MCH pathway exhibited significantly higher expression in tumour tissue from patients who did not relapse, including eleven genes representation of the MHC II pathway. In this study, we further investigated 24 genes in MCH pathway in prognosis of TNBC. This work will lead in future guidance in treatment of TNB based on patient’s’ gene profile and also provides means to assess prognosis in TNBC.Material and methodsForty-seven snap frozen primary TNBC tumour specimens were analysed using RNA-seq. Descriptive analysis and logistic regression model were used to identify genes that can predict TNB good prognosis (no relapsed). Odds ratio and 95% two-sided confidence intervals were presented. The optimal cut point of expression level was determined from the receiver operating characteristic analysis and sensitivity and specificity were estimated. This study has approval of Institutional Review Board.Results and discussionsMCH II genes CD74 and CIITA had significantly association with TNBC progression free survival. When TNBC patients had high CIITA, they were 10 times likely to have no relapsed than patients with low expression (odds ratio OR=10.8, 95% CI 2.8–41.9, p=0.006). The sensitivity and specificity is 75% and 78.3% respectively; TNB who had higher expression of CD74 had 3 times more likely to have no relapsed (OR=3.1, 95% CI 0.95–10.28, p=0.0609) with sensitivity and specificity of 62.5% and 65.2% respectively. We used multivariable approach with all 24-gene panel and identified three genes, CIITA, CTSH and KRT14 together can predict no relapsed with 87.5% sensitivity 78.3%. The accuracy is 83% if TNBC had high expression of CIITA, CTSH and KRT14. With a total of 47 patients, we predicted 17 out 22 relapsed, and 21 out 25 no relapsed correctly. The results was validated using the public microarray data from 199 patients with TNBC confirmed.ConclusionHigher expression of genes in MCII pathway, e.g. CIITA, CD74, not only associated with TNBC progression free survival, they also have high accuracy to predict TNBC patient’s no relapse regardless of age, race, and tumour grade and tumour stage.