Corpus carcinoma is the most common gynecological malignant tumor and the fourth most common malignant tumor after breast cancer, colorectal cancer, and lung cancer in women in developed countries. According to the American Cancer Society, there are expected to be 66,570 new diagnoses and 12,940 deaths in 2021(1). The existing cancer markers, such as serum CA125 and CA199, are not enough to meet the needs of precision medicine. Therefore, new biomarkers are needed to accurately diagnose corpus carcinoma.
The complement system is an essential part of the innate immune system, in which many proteins work in a cascade, forming a complex pore structure. Complement proteins in plasma are mainly synthesized in hepatocytes, but also secreted by endothelial cells, leukocytes and epithelial cells.(2–5).In extravascular tissues, complement proteins are also involved in intercellular communication, organ regeneration, Angiogenesis, epithelial-mesenchymal transformation, and cell migration. Markiewski et Al showed that regulatory t cells (Tregs) in breast tumors can be activated by C5a receptor protein in the tumor microenvironment, which is a component of the classical complement cascade (5). In addition, peptide antagonists of C5a receptor can enhance the anti-tumor response of CD8 T cells, which is as effective as Taxol in delaying tumor growth.
C7 belongs to the complement system, which is composed of natural complement, complement controlling component and complement receptor. It is an important part of the natural immune system and plays a vital role in the coordination of natural immune and adaptive immune responses, c7 is a 93-kDa serum glycoprotein encoded by the C 7 gene. C7 and other terminal complement components (C5B, C6, C8 and C9) membrane attack form complex (Mac), which functions complement the lethality unit system(6). The insertion of C7 into the cell membrane was identified as a key step in the formation of MAC (Membrane Attack by Complement, MAC) (7).
C7 has been involved in the development of several malignancies in previous studies. It has been reported that the expression of C7 is increased in normal human tissues, but significantly decreased in human esophageal, colon and kidney cancer tissues (8). In addition, the expression of C7mRNA decreased gradually in normal, benign, borderline and malignant ovarian tissues, and there was a negative correlation between C7 expression and tumor grade in patients with ovarian cancer(9). Meanwhile, some researchers believe that C7 can promote the progression of cancer. The expression of C7 was up-regulated in ovarian cancer, while knockout of C7 gene decreased the proliferation of ovarian cancer cells(10).The significant up-regulation of C7 protein is also a necessary condition for maintaining the dryness of stem cells in liver tumor initiation cells(11).
C7 has recently been shown to be associated with the prognosis of patients with prostate cancer and to be a novel prognostic biomarker and immunotherapeutic target for prostate cancer(12). In addition, C7 is an independent prognostic factor for breast cancer, and patients with high C7 expression are not susceptible to Te (taxane and anthracyclines)-based chemotherapy(13).
Until now, the role of C7 in human corpus carcinoma was
unknown. In this study, we firstly identified C7 was an independent prognostic factor of corpus carcinoma and its expression was significantly higher in lower 5-year survival patients compared with higher 5-year survival patients. By mRNA expression analysis of a large population of 406 cases, we provided the first clinical evidence that a high expression of C7 promoted breast cancer progression.