The nuclear expression of poly (ADP-ribose) polymerase-1 (PARP1) in invasive primary breast tumors is associated with chemotherapy sensitivity

Abstract

It has been reported that expression levels of DNA repair genes are frequently associated with chemotherapy sensitivity and prognosis in breast cancer (BC) subtypes. The poly (ADP-ribose) polymerase-1 (PARP1), one of the major DNA single-strand break (SSBs) repair proteins, has been demonstrated a role in BC development. Because many of the chemotherapeutic agents target the tumor cell DNA, a DNA damage repair protein function is expected to impact therapeutic responses. However, the predictive effect of PARP1 in neoadjuvant chemotherapy (NC) treated BC is still controversial. To investigate whether PARP1 expression in BC is a possible biomarker to predict chemotherapeutic response, we assessed PARP1 expression in BC specimens based on collagen gel droplet embedded culture-drug sensitivity test (CD-DST) (in vitro) results and chemotherapeutic response of NC (in vivo). The surgical specimens from 108 patients with BC were recruited for CD-DST and PARP1 immunohistochemistry. We found that higher nuclear PARP1 (nPARP1) expression correlated with increased in vitro chemosensitivity against docetaxel (p=0.001) and epirubicin (p=0.022) based on CD-DST results. We also found that tumors with high nPARP1 expression were more sensitive to anthracycline/taxane based chemotherapy and associated with pathologic responses to NC using univariate and multivariate analyses (p=0.019 and p=0.037, respectively). Taken together, we conclude that nuclear expression of PARP1 is a useful marker to predict BC therapeutic responses.