TAT-2 can act as a growth stimulator by binding to cell receptors to activate receptors and promote cell proliferation. Consequently, TAT-2 is believed to be an important factor in promoting tumor invasion. Chemical modifications by tetracycline, doxycycline, and TATI can inhibit the migration of cancer cells by down-regulating the expression or activity of TAT-2, thus suggesting that TAT-2 may be a potential therapeutic target for tumors and that reducing the expression of TAT-2 may be useful for tumor treatment(17). In addition, previous studies have shown that TAT-2 can be used for the preliminary diagnosis and prognosis of certain types of cancers. Paju et al.(18) found that the preoperative elevation of trypsin-2-API in serum is a strong prognostic factor for advanced epithelial ovarian cancer and demonstrated that the expression of TAT-2 plays a certain role in the development of ovarian cancer. Furthermore, immunohistochemically detected trypsin is associated with the recurrence and poor prognosis of human colorectal cancer(19). Lempinen et al.(5) found that TAT-2 in serum is highly accurate in differentiating between cholangiocarcinoma and primary sclerosing cholangitis.
In the past, scholars usually used ELISA and radioimmunoassay to detect TAT-2 levels in sera from patients(1, 20, 21). In ELISA, enzymes are used to tag antigens or antibodies. However, high-activity enzymes are strictly required in this assay. In addition, ELISA needs 2–3 h to detect serum samples, has low sensitivity, can only perform semiquantitative detection, and is unsuitable for application in clinical detection(22, 23). The lack of stability and the short ranges of measurement are two other reasons why ELISA cannot be used in clinical testing. Therefore, developing a serum TAT-2 detection method with increased sensitivity and accuracy is crucial. In this research, we used TRFIA for detection. TRFIA has the advantages of high sensitivity and rapid detection and is thus suitable for clinical detection.
In this work, a method for the detection of TAT-2 in sera by TRFIA was established for the first time and preliminarily applied to detect the level of TAT-2 in sera from patients with cancer. The diagnostic value and clinical application of TAT-2 were evaluated by comparing the levels of TAT-2 in healthy subjects and patients with cancer. The positive rate of TAT-2 was found to be more than 40% in patients with lung cancer, liver cancer, nasopharyngeal cancer, cholangiocarcinoma, brain cancer, and pancreatic cancer, and the positive rates of this tumor marker in patients with related cancers were 20%-50%, indicating that the diagnostic value of TAT-2 in lung cancer, liver cancer, nasopharyngeal cancer, cholangiocarcinoma, brain cancer, and pancreatic cancer was close to that of general tumor markers. TAT-2 concentrations are associated with MMP-9 activation in ovarian cancer(24), and MMP-2 and − 9 are type IV collagenases that participate in tumor invasion; the expression of the inhibitor of MMP-2 is associated with lung cancer(25) and may be one of the reasons for the elevated TAT-2 levels in patients with lung cancer. Hedström et al.(11) showed that elevated TAT-2 and TAT-2-AAT levels in serum are the most common feature in patients with hepatobiliary and pancreatic tumors. Our experimental results were consistent with previous results. the involvement of TAT-2 in the pathogenesis of nasopharyngeal cancer and brain cancer has not been revealed. In addition, through the literature, we found that nasopharyngeal carcinoma and brain cancer lack an appropriate clinical serological marker. Clinical imaging and immunohistochemical methods are usually used for the diagnosis of these malignancies(26, 27). However, due to small pathological changes or low resolution, clinical imaging methods may cause misdiagnosis. Immunohistochemistry requires pathology detection through biopsy, which is a complicated process and may destroy tumor tissues, thus leading to the metastasis of tumor cells into the blood. Through TAT-2-TRFIA detection, we found that the TAT-2 positive rates of patients with nasopharyngeal cancer and brain cancer were approximately 50% and there were few other serological indicators that can reach this level. This result indicated that TAT-2 might be helpful in the diagnosis of nasopharyngeal cancer and brain cancer and might become a new diagnostic index with a simple detection process that could be used in combination with clinical imaging methods to improve the accuracy of diagnosis. In addition, we found that in lung cancer, the positive rates of CEA and CA-125 were higher than other tumor markers, and the positive rate could be improved significantly after combined use with TAT-2. In liver cancer, AFP is a tumor marker of liver cancer with a high positive rate, and the positive rate can be increased by 30% after combined use with TAT-2. In cholangiocarcinoma, the positive rates of CEA, CA-125 and CA-199 were all high, which was consistent with the experimental results of predecessors(28). The positive rates of CEA and CA-199 could improve obviously after combined use with TAT-2, while the positive rate of CA-125 was less improved. In pancreatic cancer, and the positive rate of CA-199 is high, up to 83.3%, but when combined with TAT-2, the positive rate hardly increases.
In conclusion, we successfully established a serological detection method for TAT-2 and found that this detection method can be used for cancer diagnosis. The combined use of TAT-2 and other tumor markers could further improve the positive rate of detection and help to screen patients with cancer.