Chu Jinah, Min Kyueng-Whan, Kim Dong-Hoon, Son Byoung Kwan, Kim Hyung Suk, Jung Un Suk, Kwon Mi Jung, Do Sung-Im
Department of Pathology, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, 29 Saemunanro, Jongno-gu, Seoul, Republic of Korea.
Department of Pathology, Hanyang University Guri Hospital, Hanyang University College of Medicine, Guri, Gyeonggi-do, Republic of Korea.
Breast Cancer. 2023 Mar;30(2):259-270. doi: 10.1007/s12282-022-01419-0. Epub 2022 Dec 7.
PTPRF-interacting protein alpha 1 (PPFIA1) plays an important role as a regulator of cell motility and tumor cell invasion and is frequently amplified in breast cancer. The aim of this study was to investigate the clinicopathologic features, survival, anticancer immunities and specific gene sets related to high PPFIA1 expression in patients with breast cancer. We verified the importance of PPFIA1 and survival rates using machine learning and identified drugs that can effectively reduce breast cancer cells with high PPFIA1 expression.
This study analyzed clinicopathologic factors, survival rates, immune profiles and gene sets according to PPFIA1 expression in 3457 patients with breast cancer from the Kangbuk Samsung Medical Center cohort (456 cases), Molecular Taxonomy of Breast Cancer International Consortium (1904 cases) and The Cancer Genome Atlas (1097 cases). We applied gene set enrichment analysis (GSEA), in silico cytometry, pathway network analyses, in vitro drug screening, and gradient boosting machine (GBM) analysis.
High PPFIA1 expression in breast cancer was associated with worse prognosis, with reduced tumor-infiltrating lymphocytes, especially CD8+ T cells, and increased PD-L1 expression. In pathway network analysis, PPFIA1 was linked directly to the tyrosine-protein phosphatase pathway and indirectly to immune pathways. The importance of PPFIA1's association with survival in GBM analysis was higher than that of perineural and lymphovascular invasion. In in vitro drug screening, expression of PPFIA1 on mRNA level positively correlated with sensitivity of cell lines to erlotinib.
High PPFIA1 in patients with breast cancer is related to poor prognosis and decreased anticancer immune response, and erlotinib may be promising for development of therapeutic approaches in patients with tumors overexpressing PPFIA1.
PTPRF相互作用蛋白α1（PPFIA1）作为细胞运动和肿瘤细胞侵袭的调节因子发挥着重要作用，且在乳腺癌中经常扩增。本研究的目的是调查乳腺癌患者中与高PPFIA1表达相关的临床病理特征、生存率、抗癌免疫及特定基因集。我们使用机器学习验证了PPFIA1与生存率的重要性，并确定了可有效降低高PPFIA1表达乳腺癌细胞的药物。
本研究分析了来自江北三星医疗中心队列（456例）、国际乳腺癌分子分类联盟（1904例）和癌症基因组图谱（1097例）的3457例乳腺癌患者根据PPFIA1表达的临床病理因素、生存率、免疫谱和基因集。我们应用了基因集富集分析（GSEA）、虚拟细胞术、通路网络分析、体外药物筛选和梯度提升机（GBM）分析。
乳腺癌中高PPFIA1表达与较差的预后相关，肿瘤浸润淋巴细胞减少，尤其是CD8+ T细胞，且PD-L1表达增加。在通路网络分析中，PPFIA1直接与酪氨酸蛋白磷酸酶通路相关，并间接与免疫通路相关。在GBM分析中，PPFIA1与生存率的关联重要性高于神经周围和淋巴管浸润。在体外药物筛选中，PPFIA1在mRNA水平的表达与细胞系对厄洛替尼的敏感性呈正相关。
乳腺癌患者中高PPFIA1与预后不良和抗癌免疫反应降低相关，厄洛替尼可能有望用于开发针对PPFIA1过表达肿瘤患者的治疗方法。
