Oshi Masanori, Newman Stephanie, Murthy Vijayashree, Tokumaru Yoshihisa, Yan Li, Matsuyama Ryusei, Endo Itaru, Takabe Kazuaki
Breast Surgery, Department of Surgical Oncology, Roswell Park Comprehensive Cancer Center, Buffalo, New York, NY 14263, USA.
Department of Gastroenterological Surgery, Yokohama City University Graduate School of Medicine, Yokohama 236-0004, Japan.
Cancers (Basel). 2020 Sep 25;12(10):2758. doi: 10.3390/cancers12102758.
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 () is a negative regulator of T cell activation, and reduction in 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 expression level is associated with NAC response and prognosis in TNBC. The gene was expressed in the mammary gland, but its expression was highest in breast cancer cells among other stromal cells in a bulk tumor. expression was highest in TNBC, associated with its survival, and was its independent prognostic factor. Although high was not associated with immune function nor with any immune cell fraction, low significantly enriched cell proliferation-related gene sets in TNBC. TNBC with low achieved a significantly higher pCR rate after NAC. To the best of our knowledge, this is the first report to demonstrate that gene expression may be useful as a prognostic and predictive biomarker in TNBC.
三阴性乳腺癌（TNBC）是乳腺癌中最具侵袭性的亚型，其死亡率高于其他亚型。新辅助化疗（NAC）后的病理完全缓解（pCR）被视为预测生存的替代指标。肌醇1,4,5-三磷酸3-激酶C（）是T细胞活化的负调节因子，已知功能降低会促进川崎病。鉴于肿瘤浸润淋巴细胞在NAC中的作用，且由于TNBC在乳腺癌中具有最丰富的免疫细胞浸润，我们推测表达水平与TNBC的NAC反应和预后相关。基因在乳腺中表达，但其在整块肿瘤的其他基质细胞中，在乳腺癌细胞中的表达最高。表达在TNBC中最高，与其生存相关，是其独立的预后因素。虽然高表达与免疫功能及任何免疫细胞亚群均无关，但低表达在TNBC中显著富集细胞增殖相关基因集。NAC后，低表达的TNBC达到显著更高的pCR率。据我们所知，这是第一份证明基因表达可能作为TNBC的预后和预测生物标志物的报告。
