High Expression of Complement Component C7 Indicates Poor Prognosis of Breast Cancer and Is Insensitive to Taxane-Anthracycline Chemotherapy

Overview

Journal Front Oncol

Specialty Oncology

Date 2021 Oct 11

PMID 34631552

Citations 8

Authors

Huikun Zhang

Yawen Zhao

Xiaoli Liu

Li Fu

Feng Gu

Yongjie Ma

Affiliations

Soon will be listed here.

Abstract

Background: 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.

Methods: 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.

Results: 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.

Conclusions: 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.

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References

Dai X, Xiang L, Li T, Bai Z . Cancer Hallmarks, Biomarkers and Breast Cancer Molecular Subtypes. J Cancer. 2016; 7(10):1281-94. PMC: 4934037. DOI: 10.7150/jca.13141. View

Liu L, Li W, Li Z, Kirschfink M . Sublytic complement protects prostate cancer cells from tumour necrosis factor-α-induced cell death. Clin Exp Immunol. 2012; 169(2):100-8. PMC: 3406369. DOI: 10.1111/j.1365-2249.2012.04596.x. View

Weaver B . How Taxol/paclitaxel kills cancer cells. Mol Biol Cell. 2014; 25(18):2677-81. PMC: 4161504. DOI: 10.1091/mbc.E14-04-0916. View

Michlmayr A, Bachleitner-Hofmann T, Baumann S, Marchetti-Deschmann M, Rech-Weichselbraun I, Burghuber C . Modulation of plasma complement by the initial dose of epirubicin/docetaxel therapy in breast cancer and its predictive value. Br J Cancer. 2010; 103(8):1201-8. PMC: 2967072. DOI: 10.1038/sj.bjc.6605909. View

Tewey K, Chen G, NELSON E, Liu L . Intercalative antitumor drugs interfere with the breakage-reunion reaction of mammalian DNA topoisomerase II. J Biol Chem. 1984; 259(14):9182-7. View

Seol H, Lee S, Song J, Rhee J, Singh S, Chang S . Complement proteins C7 and CFH control the stemness of liver cancer cells via LSF-1. Cancer Lett. 2016; 372(1):24-35. PMC: 4744505. DOI: 10.1016/j.canlet.2015.12.005. View

Fosbrink M, Niculescu F, Rus V, Shin M, Rus H . C5b-9-induced endothelial cell proliferation and migration are dependent on Akt inactivation of forkhead transcription factor FOXO1. J Biol Chem. 2006; 281(28):19009-18. DOI: 10.1074/jbc.M602055200. View

Suryawanshi S, Huang X, Elishaev E, Budiu R, Zhang L, Kim S . Complement pathway is frequently altered in endometriosis and endometriosis-associated ovarian cancer. Clin Cancer Res. 2014; 20(23):6163-74. PMC: 4252715. DOI: 10.1158/1078-0432.CCR-14-1338. View

Fosbrink M, Niculescu F, Rus H . The role of c5b-9 terminal complement complex in activation of the cell cycle and transcription. Immunol Res. 2004; 31(1):37-46. DOI: 10.1385/IR:31:1:37. View

10.

Soane L, Cho H, Niculescu F, Rus H, Shin M . C5b-9 terminal complement complex protects oligodendrocytes from death by regulating Bad through phosphatidylinositol 3-kinase/Akt pathway. J Immunol. 2001; 167(4):2305-11. DOI: 10.4049/jimmunol.167.4.2305. View

11.

Ying L, Zhang F, Pan X, Chen K, Zhang N, Jin J . Complement component 7 (C7), a potential tumor suppressor, is correlated with tumor progression and prognosis. Oncotarget. 2016; 7(52):86536-86546. PMC: 5349933. DOI: 10.18632/oncotarget.13294. View

12.

Carroll M . The complement system in regulation of adaptive immunity. Nat Immunol. 2004; 5(10):981-6. DOI: 10.1038/ni1113. View

13.

Dai K, Qin F, Zhang H, Liu X, Guo C, Zhang M . Low expression of BMPRIB indicates poor prognosis of breast cancer and is insensitive to taxane-anthracycline chemotherapy. Oncotarget. 2015; 7(4):4770-84. PMC: 4826242. DOI: 10.18632/oncotarget.6613. View

14.

Ricklin D, Hajishengallis G, Yang K, Lambris J . Complement: a key system for immune surveillance and homeostasis. Nat Immunol. 2010; 11(9):785-97. PMC: 2924908. DOI: 10.1038/ni.1923. View

15.

Ogston K, Miller I, Payne S, Hutcheon A, Sarkar T, Smith I . A new histological grading system to assess response of breast cancers to primary chemotherapy: prognostic significance and survival. Breast. 2003; 12(5):320-7. DOI: 10.1016/s0960-9776(03)00106-1. View

16.

Lei S, Zheng R, Zhang S, Chen R, Wang S, Sun K . Breast cancer incidence and mortality in women in China: temporal trends and projections to 2030. Cancer Biol Med. 2021; . PMC: 8330522. DOI: 10.20892/j.issn.2095-3941.2020.0523. View

17.

MULLER-EBERHARD H . The membrane attack complex of complement. Annu Rev Immunol. 1986; 4:503-28. DOI: 10.1146/annurev.iy.04.040186.002443. View

18.

Brook N, Brook E, Dharmarajan A, Dass C, Chan A . Breast cancer bone metastases: pathogenesis and therapeutic targets. Int J Biochem Cell Biol. 2018; 96:63-78. DOI: 10.1016/j.biocel.2018.01.003. View

19.

Oka R, Sasagawa T, Ninomiya I, Miwa K, Tanii H, Saijoh K . Reduction in the local expression of complement component 6 (C6) and 7 (C7) mRNAs in oesophageal carcinoma. Eur J Cancer. 2001; 37(9):1158-65. DOI: 10.1016/s0959-8049(01)00089-2. View

20.

Sung H, Ferlay J, Siegel R, Laversanne M, Soerjomataram I, Jemal A . Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin. 2021; 71(3):209-249. DOI: 10.3322/caac.21660. View