Cervical carcinoma, endometrial carcinoma and ovarian carcinoma are the three most common gynecological malignancies, and their incidence and mortality in the world have recently been increasing[8].Their traditional treatments include surgery, chemotherapy and radiotherapy,and in recent years, tumor treatment has tended to be targeted and more precise treatment regimens[9].
In this study, PAI-1 4G/5G polymorphism and 4G/5G allelic frequency are associated with gynecological malignancies.The frequency of the PAI-1 4G/4G genotype and 4G allele in patients with malignant tumors are significantly higher than those of the control group. Individuals with 4G/4G genotype are at higher risk of gynecological malignancies than the other genotypes.YI-TORNG TEE et al. found that there was an interaction between uPA/PAI-1 genes,and women carrying the uPA/PAI-1 CC/4G4G allele had a 1.70 fold higher risk of cervical neoplasia compared with women carrying the CC/4G5G allele[10].Dominique Koensgen et al. analysed the levels of PAI-1 and histopathological results in 156 ovarian cancer patients, and found that PAI-1 might play an important role in the progression of ovarian cancer, and its high expression levels were associated with poor prognosis in patients[11]. Yıldırım Malik Ejder et al. screened the PAI-1 4G/5G polymorphism and peripheral blood PAI-1 levels in 82 patients with endometrial cancer and 76 female healthy controls, it was concluded that PAI-1 and PAI-1 4G/5G polymorphism might affect the formation of endometrial cancer[12].In conclusion, consistent with the results of this study, it has also been confirmed that the PAI-1 4G/4G genotype and 4G allele are associated with the formation of gynecological malignant tumors.
PAI-1 mainly plays an important role in reducing plasminogen activity, leading to poor fibrinolysis[13].Therefore, we speculate that PAI-1 affects the formation and growth of gynecological malignant tumors by regulating plasminogen activity. Masakazu Sa et al. found that cancer cells adhered to basal membrane secreted abundant PAI-1 to protect the extracellular matrix from degrading, so as to protect the extracellular matrix for cell migration[14].This research result is consistent with that in this study, the significantly higher incidence of gynecological malignant tumors in the PAI-1 4G/4G genotype compared to the other genotypes. Meanwhile, PAI-1 also participates in the regulation of cell adhesion, detachment, and migration, playing an important role in the development and invasion of malignant tumors[15].Another speculation is that PAI-1 affects the formation and growth of malignant tumors through the regulation of angiogenesis. Asmaa Anwar Ismail et al. found that PAI-1 promoted tumor angiogenesis and invasion by interacting with proteases in mice deficient for PAI-1[16].We speculate that the PAI-1 4G/5G polymorphism which regulates the level of PAI-1, plays a role in the formation of gynecological malignant tumors by participating in the regulation of cell adhesion, detachment, and migration, or by participating in angiogenesis. Meanwhile, PAI-1 may also be involved in the formation and invasion of tumor cells.
At present, the application prospects of PAI-1 in clinical practice are very broad, not only in gynecological malignant tumors, but be of great significance for the screening, diagnosis, evaluation of treatment responses, and prediction of prognosis for various diseases. PAI-1 is an important factor in regulating the formation of thrombi in the blood vessels, and it plays an important role in the prevention and treatment of cardiovascular diseases.By inhibiting the PAI-1, it can effectively prevent and treat the occurrence of some diseases, such as cardiovascular diseases and stroke[17].A great deal of studies have also shown that serum PAI-1 level is closely related to the growth, metastasis, and invasion of tumors. At the same time, PAI-1 level can be used to screen early stage of lung cancer and predict treatment response of breast cancer[18]. PAI-1 4G/5G gene is clinically used as a prognostic significance in early node-negative luminal HER2-negative breast cancer patients [19]. In a word, PAI-1 is of great significance in clinical applications.
However, explore the mechanism of the different genotypes of PAI-1 4G/5G in the occurrence and development of cancer, providing a more scientific evidence for the diagnosis and treatment of cancer. Meanwhile, assess the individual’s cancer risk and make reasonable intervention measures according to the PAI-1 4G/5G genotypes. More randomized controlled researchs with large samples and multiple centers are still needed.