Zhang Huikun, Zhao Yawen, Liu Xiaoli, Fu Li, Gu Feng, Ma Yongjie
Department of Tumor Cell Biology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin, China.
Tianjin's Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China.
Front Oncol. 2021 Sep 24;11:724250. doi: 10.3389/fonc.2021.724250. eCollection 2021.
Breast cancer is the most commonly diagnosed cancer worldwide. However, the well-known biomarkers are not enough to meet the needs of precision medicine. Novel targets are desirable and highly valuable for improved patient survival. In this regard, we identified complement component C7 as one of the candidates based on data from the OCOMINE database.
C7 expression was examined by immunohistochemistry in 331 cases of invasive ductal carcinoma (IDC), 45 cases of ductal carcinoma (DCIS), and 52 cases of non-neoplastic tissues adjacent to tumor. Then, C7 expression was further confirmed by Western blot analysis based on IDC specimens and non-neoplastic breast specimens. The relationship between the C7 expression and prognosis of breast cancer patients was analyzed in order to investigate the function of C7 in breast cancer patients. Meanwhile, we also analyzed the relationship between the C7 expression and prognosis of 149 patients treated with conventional TE (taxane and anthracycline)-based chemotherapy. Then, a cohort of patients (22 cases) treated with TE neoadjuvant chemotherapy was used to further confirm the relationship between the C7 expression and TE-based chemosensitivity.
In our present study, we reported for the first time that C7 was an independent prognostic factor of breast cancer and C7 expression of IDC tissues was higher than non-neoplastic tissues adjacent to tumor and DCIS. In a cohort of 331 IDC patients, high expression of C7 indicated poor prognosis especially in the triple negative subtype and luminal B subtype. Furthermore, C7 was also a promoting factor for triple negative subtype patients to develop bone metastasis. Meanwhile, we provided the first evidence that patients with high C7 expression were insensitive to TE (taxane and anthracycline)-based chemotherapy by analyzing a cohort of 149 patients treated with TE-based chemotherapy and another cohort of 22 patients treated with TE neoadjuvant chemotherapy.
In summary, high expression of C7 may promote breast cancer development and might be insensitive to TE-based chemotherapy. Our present study laid a foundation to help clinicians improve the identification of patients for TE-based chemotherapy by C7 in the era of precision medicine.
乳腺癌是全球最常被诊断出的癌症。然而,众所周知的生物标志物不足以满足精准医学的需求。新型靶点对于提高患者生存率具有重要意义且极具价值。在这方面,我们基于OCOMINE数据库的数据,将补体成分C7确定为候选靶点之一。
通过免疫组织化学检测331例浸润性导管癌(IDC)、45例导管原位癌(DCIS)以及52例肿瘤旁非肿瘤组织中C7的表达。然后,基于IDC标本和非肿瘤性乳腺标本,通过蛋白质印迹分析进一步证实C7的表达。分析C7表达与乳腺癌患者预后的关系,以研究C7在乳腺癌患者中的作用。同时,我们还分析了149例接受基于紫杉烷和蒽环类药物(TE)的传统化疗患者中C7表达与预后的关系。然后,使用一组接受TE新辅助化疗的患者(22例)进一步证实C7表达与基于TE的化疗敏感性之间的关系。
在本研究中,我们首次报道C7是乳腺癌的独立预后因素,IDC组织中C7的表达高于肿瘤旁非肿瘤组织和DCIS。在331例IDC患者队列中,C7高表达表明预后较差,尤其是在三阴性亚型和管腔B亚型中。此外,C7也是三阴性亚型患者发生骨转移的促进因素。同时,通过分析149例接受基于TE化疗的患者队列和另一组22例接受TE新辅助化疗的患者,我们首次提供了证据表明C7高表达的患者对基于TE(紫杉烷和蒽环类药物)的化疗不敏感。
总之,C7高表达可能促进乳腺癌发展,并且可能对基于TE的化疗不敏感。我们目前的研究为在精准医学时代帮助临床医生通过C7改善基于TE化疗患者的识别奠定了基础。