ITPKC as a Prognostic and Predictive Biomarker of Neoadjuvant Chemotherapy for Triple Negative Breast Cancer

Abstract

Triple negative breast cancer (TNBC) is the most aggressive subtype of breast cancer with higher mortality than the others. Pathological complete response (pCR) to neoadjuvant chemotherapy (NAC) is considered as a surrogate to predict survival. Inositol 1,4,5-trisphosphate 3-kinase C (<i>ITPKC</i>) is a negative regulator of T cell activation, and reduction in <i>ITPKC</i> function is known to promote Kawasaki disease. Given the role of tumor infiltrating lymphocytes in NAC and since TNBC has the most abundant immune cell infiltration in breast cancer, we hypothesized that the <i>ITPKC</i> expression level is associated with NAC response and prognosis in TNBC. The <i>ITPKC</i> gene was expressed in the mammary gland, but its expression was highest in breast cancer cells among other stromal cells in a bulk tumor. <i>ITPKC</i> expression was highest in TNBC, associated with its survival, and was its independent prognostic factor. Although high <i>ITPKC</i> was not associated with immune function nor with any immune cell fraction, low <i>ITPKC</i> significantly enriched cell proliferation-related gene sets in TNBC. TNBC with low <i>ITPKC</i> achieved a significantly higher pCR rate after NAC. To the best of our knowledge, this is the first report to demonstrate that <i>ITPKC</i> gene expression may be useful as a prognostic and predictive biomarker in TNBC.