McDonald Kerry-Ann, Oshi Masanori, Kawaguchi Tsutomu, Qi Qianya, Peng Xuan, Yamada Akimitsu, Opyrchal Mateusz, Liu Song, Yao Song, Otsuji Eigo, Yan Li, Endo Itaru, Takabe Kazuaki
Department of Surgical Oncology, Roswell Park Comprehensive Cancer Center Buffalo, NY 14263, USA.
Department of Gastroenterological Surgery, Yokohama City University Graduate School of Medicine Yokohama, Kanagawa 236-0027, Japan.
Am J Cancer Res. 2021 Nov 15;11(11):5388-5401. eCollection 2021.
Some may think that prediction of metastasis is meaningless since metastatic breast cancer is currently incurable. We argue that effective identification of developing metastasis will enable us to design and conduct clinical trials specifically targeting those patients at high risk. The current study sought to generate the KAM score by 4 genes (, and ) overexpressed in primary breast cancer that developed metastasis to bone compared with matched controls without metastasis longer than 10 years. A high KAM score was prognostic of poor overall (OS), disease free survival (DFS), and disease specific survival (DSS) in the METABRIC, and OS in the GSE96058 cohorts. A high KAM score was significantly associated with clinical aggressiveness, such as high American Joint Committee Cancer (AJCC) stage, lymph node metastasis, Nottingham pathological grade, and triple negative breast cancer (TNBC). Subgroup analysis revealed that a high KAM score was associated with worse OS in ER-positive/HER2-negative breast cancer in both cohorts. A high KAM breast cancer enriched all 5 cell proliferation-related gene sets of the Hallmark collection and interferon (IFN)-γ response gene sets. Furthermore, a high KAM breast cancer was significantly infiltrated with a high fraction of not only anti-cancer but also pro-cancer immune cells and associated with high level of cytolytic activity. Finally, a high KAM breast cancer was significantly associated with lung metastasis. In conclusion, we developed KAM score using 4 gene expressions that predict lung metastasis and patient survival in breast cancer.
有些人可能认为转移预测毫无意义，因为转移性乳腺癌目前无法治愈。我们认为，有效识别正在发生的转移将使我们能够设计并开展专门针对高危患者的临床试验。当前研究试图通过在发生骨转移的原发性乳腺癌中过表达的4个基因（ 、 、 和 ）生成KAM评分，这些原发性乳腺癌与未发生转移且生存期超过10年的配对对照相比发生了骨转移。在METABRIC队列中，高KAM评分可预测总体生存期（OS）、无病生存期（DFS）和疾病特异性生存期（DSS）较差，在GSE96058队列中可预测OS较差。高KAM评分与临床侵袭性显著相关，如美国癌症联合委员会（AJCC）高分期、淋巴结转移、诺丁汉病理分级和三阴性乳腺癌（TNBC）。亚组分析显示，在两个队列的雌激素受体阳性/人表皮生长因子受体2阴性乳腺癌中，高KAM评分与较差的OS相关。高KAM评分的乳腺癌富集了Hallmark集合的所有5个细胞增殖相关基因集和干扰素（IFN）-γ反应基因集。此外，高KAM评分的乳腺癌不仅有高比例的抗癌免疫细胞浸润，还有高比例的促癌免疫细胞浸润，且与高水平的细胞溶解活性相关。最后，高KAM评分的乳腺癌与肺转移显著相关。总之，我们利用4个基因表达开发了KAM评分，该评分可预测乳腺癌的肺转移和患者生存情况。
