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Tissue peptide-specific antigen TPS, a specific indicator of proliferative activity of tumor cells

Zecen Biotech 2022-12-28 19:18 Published in Jiangsu

Tissue polypeptide-specific antigen (TPS) is an M3 antigenic determinant cluster on the cytokeratin 18 fragment, and the level of TPS in serum is a more specific indicator of tumor cell division and proliferative activity.

Studies have shown the unique value of TPS in early diagnosis of malignant tumors, forecasting recurrence and metastasis, and evaluating prognosis.

TPS Introduction -

Specific indicators of proliferative activity of tumor cells

Tissue polypeptide specific antigen (TPS) is an antigenic epitope on the 18 fragment of cytokeratin (CK) that binds to the M3 monoclonal antibody, called the M3 antigenic determinant cluster, identified by Bjorklund B et al. 1990.

TPS is expressed in small amounts in some actively growing normal somatic cells (e.g., hepatocytes, urogenital tract cells) and is highly expressed in malignant tumors of epithelial origin and metastatic carcinomas. During the late S and G phases of the cell cycle, TPS is synthesized and released into human blood or other body fluids.

Therefore, the level of TPS in serum becomes a specific indicator of tumor cell division and proliferative activity.

TPS

"Tumor activity-dependent" markers

Unlike traditional tumor markers such as CEA, CA153, CA125, etc., TPS is "tumor activity-dependent", and its serum level is related to the number of cells that are dividing and proliferating, i.e. to tumor activity. The serum level of TPS is related to the number of cells that are dividing and proliferating, i.e. to the tumor activity.

On the other hand, CEA, CA153, CA125, etc. are "tumor volume dependent", which are related to the tumor load, i.e. the number of tumor cells.

Therefore, in the early stage of tumor, before the appearance of naked eye recurrence or metastasis, the serum levels of those markers reflecting tumor volume are often low due to the low number of tumor cells, while at this time the tumor cells are actively dividing and proliferating, thus TPS can be high, thus facilitating the early diagnosis, treatment, disease monitoring and prognosis of tumor.

Application of TPS in common tumors

Breast Cancer

Part.1 Diagnostic significance

It was found that TPS levels in breast cancer patients were significantly higher than those in patients with benign tumors, and TPS levels were positively correlated with their clinical stage and lymph node metastasis, independent of patient age, histological type and grade of the tumor.

Sjorklund B, in a study of more than 3,000 breast cancers lasting 4 years, found that TPS is a marker of tumor cell activity, independent of tumor load, and that TPS in combination with traditional markers reflecting tumor load may lead to a more comprehensive diagnosis of tumors.

Part.2 Prediction of recurrence and metastasis

TPS was found to be a marker of tumor cell activity that, when combined with traditional markers reflecting tumor load, increased the sensitivity of detecting recurrence.

Chen Yan et al. measured the serum TPS and CA153 levels in 62 breast cancer patients (32 of them were metastatic recurrence after treatment) and observed the changes of tumor markers after treatment in 11 cases of metastatic breast cancer. The results showed that the sensitivity of TPS for metastatic breast cancer was 81.3%, which was significantly higher than that of CA153 (P<0.01); the specificity of CA153 was 95.5%, which was significantly higher than that of TPS (P<0.01); and the effectiveness of the combination of the two was significantly increased (P<0.01). Therefore, the combination of TPS and CA153 can improve the effectiveness of diagnosing breast cancer metastasis, and the combination is the best combination for monitoring metastatic breast cancer.

Part.3 Efficacy monitoring

The outcome of breast cancer treatment is related to the survival period and quality of life of patients, and TPS has a unique role in judging the efficacy of breast cancer.

Einarsson et al. reported that TPS decreased more than CA153 in patients in complete or partial clinical remission, and therefore concluded that TPS is a better monitor than CA153 for patients with metastatic breast cancer.

A study by Wang Ke et al. on the trend of tumor marker levels in breast cancer patients before and after radiotherapy showed that TPS levels increased most significantly in those who were not effective in treatment. Those whose serum TPS did not decrease or increased after chemotherapy indicated that there was no significant change in tumor cell activity and they were not sensitive to chemotherapy, so clinical consideration should be given to changing the treatment regimen.

Part.4 Prognostic judgment

Barak et al. concluded that TPS is one of the best prognostic indicators for breast cancer, with CA153 detecting metastases 3.9 months earlier, CEA 1.8 months earlier, and TPS 6.8 months earlier; the median survival time was 815 days for those with low levels of TPS and 332 days for those with high levels of TPS. Serum TPS levels are of great value in determining the prognosis of breast cancer patients.

Ovarian Cancer

Part.1 Diagnostic significance

Padungsut et al. measured serum TPS levels in 92 patients with clinically diagnosed ovarian tumors treated surgically, and 28.8% of the 52 benign masses diagnosed according to postoperative pathology had serum TPS exceeding the normal reference value of 80 U/L.The diagnostic sensitivity was 90.0%, specificity was 71.2%, positive predictive value (PPV) was 70.6%, and negative predictive value (NPV) was 82.9% in 90% of 40 cases of ovarian malignant tumors. The results of this study showed that the difference in the diagnosis between benign and malignant ovarian tumors could be made on the basis of TPS>180U/L.

Part.2 Efficacy monitoring

In terms of monitoring the efficacy of chemotherapy, Senapad et al. performed 6 cycles of chemotherapy followed by surgery in 33 patients with advanced ovarian cancer (stage III-IV). Serum TPS and CA125 concentrations were measured at the 1st, 3rd and 5th chemotherapy sessions and before surgery. The results showed that the TPS levels decreased linearly after chemotherapy.

Part.3 Prognostic judgment

Van Dalen et al. divided ovarian cancer patients receiving chemotherapy into two groups according to FIGO staging: one group for stages I and II and one group for stages III and IV, and used the Kaplan Meier survival curve method to compare 2-year survival rates with TPS levels.

The 2-year survival rate was 49% for patients with serum TPS <80U/L after multiple cycles of chemotherapy in stage III and IV patients and only 19% for patients with TPS >80U/L (p<0.01). If combined with CA125 (<35U/ml as reference value), the 2-year survival rate was 63% for patients with (TPS+CA125)<115 and 17% for patients with >115 (P<0.01), suggesting that TPS combined with CA125 has some significance in determining the prognosis of patients with advanced ovarian cancer after chemotherapy.

Lung Cancer

Part.1 Diagnostic significance

A study by Qiu-Lin Liao et al. showed that TPS was highly expressed in the serum of lung cancer patients, significantly higher than that of normal controls, with a positive detection rate of 80.6%, significantly higher than that of CEA at 37.5%; however, TPS was less expressed in the group with benign lung disease and normal controls, indicating that TPS has important clinical value for the diagnosis of lung cancer.

Part.2 Efficacy monitoring

In terms of disease monitoring, Nisman et al. monitored changes in serum TPS in 94 patients with non-small cell lung cancer and found a 72.2% agreement between TPS and clinical response to treatment. Ho et al. followed 60 patients with lung squamous cancer surgery for 1 year and measured serum TPS concentrations at 1 week and 1, 3, 6, 9, and 12 months postoperatively. The mean TPS levels were found to be significantly higher in the recurrence group than in the no recurrence group at any period.

Part.3 Prognostic judgment

For the relationship between TPS levels and prognosis, Nisman et al. reported the results of a multifactorial analysis of 116 cases of non-small cell lung cancer (43 squamous, 38 adenocarcinoma and 35 large cell carcinoma), the relative risk of adenocarcinoma TPS levels and survival RR=3.0, P=0.02; while for CEA RR=5.5; P=0.004; in squamous carcinoma only TPS was associated with prognosis, RR =2.3, P=0.03; in large cell carcinoma, TPS and CEA were not associated with prognosis.

Summary

TPS is a specific indicator of proliferative activity of tumor cells, especially reflecting the active degree of epithelial-derived tumor cells. Combined with the measurement of markers reflecting tumor volume, it can make the diagnosis of tumor more comprehensive, i.e. not only understanding the size of tumor load, but also knowing how active its tumor is.

Compared to clinical criteria, TPS is the earliest signal of disease progression and provides advance warning of disease progression and prognosis at the subclinical stage.TPS can be used to select and evaluate cancer treatment options, improve economic benefits, monitor disease, and predict tumor recurrence and metastasis.

From the analysis of current clinical study results, compared with other tumor markers, TPS is not outstanding in the independent diagnostic effectiveness of most epithelial-derived tumors, but it has unique value in monitoring tumor efficacy, prognosis judgment, and predicting tumor metastasis and recurrence.