Sklias Thodoris, Vardas Vasileios, Pantazaka Evangelia, Christopoulou Athina, Georgoulias Vassilis, Kotsakis Athanasios, Vasilopoulos Yiannis, Kallergi Galatea
Laboratory of Genetics, Section of Genetics, Cell Biology and Development, Department of Biology, University of Patras, 26504 Patras, Greece.
Laboratory of Biochemistry/Metastatic Signaling, Section of Genetics, Cell Biology and Development, Department of Biology, University of Patras, 26504 Patras, Greece.
Cancers (Basel). 2022 Mar 29;14(7):1731. doi: 10.3390/cancers14071731.
and PARP are involved in DNA damage repair pathways. mutations have been linked to higher likelihood of triple negative breast cancer (TNBC). The aim of the study was to determine PARP-1 expression and mutations in circulating tumor cells (CTCs) of BC patients. Fifty patients were enrolled: 23 luminal and 27 TNBC. PARP expression in CTCs was identified by immunofluorescence. Genotyping was performed by PCR-Sanger sequencing in the same samples. PARP-1 expression was higher in luminal (61%) and early BC (54%), compared to TNBC (41%) and metastatic (33%) patients. In addition, PARP-1 distribution was mostly cytoplasmic in luminal patients ( = 0.024), whereas it was mostly nuclear in TNBC patients. In cytokeratin (CK)-positive patients, those with the CKPARP phenotype had longer overall survival (OS, log-rank 0.046). Overall, nine mutations were detected; M1 and M2 were completely new and M4, M7 and M8 were characterized as pathogenic. M7 and M8 were predominantly found in metastatic TNBC patients ( = 0.014 and = 0.002). Thus, PARP-1 expression and increased mutagenic burden in TNBC patients' CTCs, could be used as an indicator to stratify patients regarding therapeutic approaches.
聚（ADP - 核糖）聚合酶（PARP）参与DNA损伤修复途径。基因突变与三阴性乳腺癌（TNBC）的较高发病可能性有关。本研究的目的是确定乳腺癌（BC）患者循环肿瘤细胞（CTC）中PARP - 1的表达及基因突变情况。共招募了50名患者：23名腔面型和27名三阴性乳腺癌患者。通过免疫荧光鉴定CTC中PARP的表达。在相同样本中通过PCR - Sanger测序进行基因分型。与三阴性乳腺癌患者（41%）和转移性患者（33%）相比，PARP - 1在腔面型患者（61%）和早期乳腺癌患者（54%）中的表达更高。此外，PARP - 1在腔面型患者中的分布大多在细胞质中（P = 0.024），而在三阴性乳腺癌患者中大多在细胞核中。在细胞角蛋白（CK）阳性患者中，具有CK / PARP表型的患者总生存期更长（OS，对数秩检验P = 0.046）。总体而言，检测到9个突变；M1和M2是全新的，M4、M7和M8被鉴定为致病性突变。M7和M8主要在转移性三阴性乳腺癌患者中发现（P = 0.014和P = 0.002）。因此，三阴性乳腺癌患者CTC中PARP - 1的表达及诱变负担增加，可作为对患者治疗方法进行分层的指标。
