Shin Eunju, Ryu Jewon, Yoo Tae-Kyung, Lee Sae Byul, Kim Jisun, Chung Il Yong, Ko Beom Seok, Kim Hee Jeong, Lee Jong Won, Lee Jun Hyeong, Kim Kyunggon, Lee Sang-Wook, Son Byung Ho
Division of Breast Surgery, Department of Surgery, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea.
Department of Convergence Medicine, Asan Medical Center, Seoul, Korea.
Sci Rep. 2025 Aug 20;15(1):30658. doi: 10.1038/s41598-025-10546-5.
Progesterone-induced blocking factor 1 (PIBF1) is linked to pregnancy-induced immunity and tumor evasion of maternal immunity. PIBF1 is overexpressed in several cancers, including breast, cervical, and lymphoma. However, limited research is available on the role of PIBF1 in breast cancer and its clinical outcomes. Therefore, we investigated the relationship between PIBF1 expression, prognosis, and its impact on chemotherapy response. Samples from 231 patients with high-risk triple-negative breast cancer (TNBC) who underwent surgery between 2008 and 2013 with lymph node metastasis and underwent taxane-based adjuvant chemotherapy were collected. Additionally, 238 non-TNBC patients matched to TNBC patients were selected. Immunohistochemical detection of the PIBF1 protein in tissues was conducted using a cut-off value of 3 (intensity plus proportion). Kaplan-Meier survival analysis assessed the probability of overall survival (OS). Using the clonogenic unit assay and knockdown methodologies in breast cancer cell lines, we examined the correlation between PIF1 expression and chemosensitivity. In a study of 469 patients with breast cancer, non-TNBC (n = 238) and TNBC (n = 231), those with PIBF1 expression manifested a lower histologic grade (p < 0.001), reduced p53 (p < 0.001) and decreased Ki-67 (p < 0.001) compared with their non-expressing counterparts. A significant difference in OS for patients with PIBF1 was observed, with non-TNBC patients showing superior outcomes. PIBF1 expression showed a relation with a better prognosis, and the statistical significance was borderline (hazard ratio = 0.44, 95% confidence interval = 0.18-1.11, p = 0.082). A correlation between PIBF1 expression in breast cancer cell lines (BT549, HCC70, BT20, and HS578T) and their sensitivity to paclitaxel was shown in vitro, with certain cell lines showing significant viability reductions and also resisting the treatment after PIBF1 knockdown. We observed a correlation between PIBF1 expression and improved prognosis in breast cancer patients with nodal metastasis undergo taxane-based chemotherapy, particularly in the non-TNBC cohort. We discerned a relationship between PIBF1 and chemosensitivity in our in vitro studies. These findings suggest the potential usefulness of PIBF1 as a predictive marker for guiding therapeutic approaches.
孕酮诱导阻断因子1(PIBF1)与妊娠诱导的免疫以及母体免疫的肿瘤逃逸有关。PIBF1在包括乳腺癌、宫颈癌和淋巴瘤在内的多种癌症中过度表达。然而,关于PIBF1在乳腺癌中的作用及其临床结局的研究有限。因此,我们研究了PIBF1表达、预后及其对化疗反应的影响之间的关系。收集了2008年至2013年间接受手术且有淋巴结转移并接受紫杉类辅助化疗的231例高危三阴性乳腺癌(TNBC)患者的样本。此外,还选择了与TNBC患者匹配的238例非TNBC患者。使用截断值为3(强度加比例)对组织中的PIBF1蛋白进行免疫组织化学检测。采用Kaplan-Meier生存分析评估总生存(OS)概率。利用乳腺癌细胞系中的克隆形成单位测定法和敲低方法,我们研究了PIF1表达与化学敏感性之间的相关性。在一项对469例乳腺癌患者(非TNBC患者238例,TNBC患者231例)的研究中,与不表达PIBF1的患者相比,PIBF1表达的患者组织学分级较低(p<0.001),p53降低(p<0.001),Ki-67降低(p<0.001)。观察到PIBF1表达患者的OS有显著差异,非TNBC患者的结局更好。PIBF1表达与较好的预后相关,统计学意义接近临界值(风险比=0.44,95%置信区间=0.18-1.11,p=0.082)。体外研究表明乳腺癌细胞系(BT549、HCC70、BT20和HS578T)中PIBF1表达与其对紫杉醇的敏感性之间存在相关性,某些细胞系在PIBF1敲低后显示出显著的活力降低且对治疗产生抵抗。我们观察到在接受紫杉类化疗的有淋巴结转移的乳腺癌患者中,PIBF1表达与预后改善相关,尤其是在非TNBC队列中。在我们的体外研究中,我们发现了PIBF1与化学敏感性之间的关系。这些发现表明PIBF1作为指导治疗方法的预测标志物具有潜在的实用性。