High Expression of Testes-Specific Protease 50 Is Associated with Poor Prognosis in Colorectal Carcinoma

Abstract

BackgroundTestes-specific protease 50 (TSP50) is normally expressed in testes and abnormally expressed in breast cancer, but whether TSP50 is expressed in colorectal carcinoma (CRC) and its clinical significance is unclear. We aimed to detect TSP50 expression in CRC, correlate it with clinicopathological factors, and assess its potential diagnostic and prognostic value.Methodology/Principal FindingsTSP50 mRNAs and proteins were detected in 7 CRC cell lines and 8 CRC specimens via RT-PCR and Western blot analysis. Immunohistochemical analysis of TSP50, p53 and carcinoembryonic antigen (CEA) with tissue microarrays composed of 95 CRCs, 20 colorectal adenomas and 20 normal colorectal tissues were carried out and correlated with clinicopathological characteristics and disease-specific survival for CRC patients. There was no significant correlation between the expression levels of TSP50 and p53 (P = 0.751) or CEA (P = 0.663). Abundant expression of TSP50 protein was found in CRCs (68.4%) while it was poorly expressed in colorectal adenomas and normal tissues (P<0.0001). Thus, CRCs can be distinguished from them with high specificity (92.5%) and positive predictive value (PPV, 95.6%). The survival of CRC patients with high TSP50 expression was significantly shorter than that of the patients with low TSP50 expression (P = 0.010), specifically in patients who had early-stage tumors (stage I and II; P = 0.004). Multivariate Cox regression analysis indicated that high TSP50 expression was a statistically significant independent risk factor (hazard ratio = 2.205, 95% CI = 1.214–4.004, P = 0.009).ConclusionOur data demonstrate that TSP50 is a potential effective indicator of poor survival for CRC patients, especially for those with early-stage tumors.

A novel cancer testis antigen target A-kinase anchor protein (AKAP4) for the early diagnosis and immunotherapy of colon cancer

“…Further, TSP50 expression was not shown to be significantly associated with CRC and the clinicopathological features. 10 In contrast, our study revealed that AKAP4 protein expression was significantly associated with late stages (III and IV, p < 0.026) of CRC patients suggesting its involvement in spread of cancer cells. Although, majority of early stage (84%, I and II) CRC patients did reveal AKAP4 expression, but no significant association was observed.…”

“…It was further documented that expression of TSP50 predicted presence of CRC with 68.4% sensitivity, 92.5% specificity, 95% PPV, and 55.2% NPV. 10 In our study, AKAP4 protein expression, based on IRS, predicted presence of CRC with 84% sensitivity, 100% specificity, 100% of PPV, and 83.33% NPV. Further, TSP50 expression was not shown to be significantly associated with CRC and the clinicopathological features.…”

“…14 None of the previous studies have reported humoral response against AKAP4 in CRC patients. Earlier, other investigations have shown humoral response against AKAP4 in small sample size patients, [6 of 19 (32%) in multiple myeloma, 15 10 of 15 (66%) in prostate cancer, 16 and 4 of 17 (23%) in NSCLC. 17 Thus, the present study has put forth an evidence that AKAP4 is highly immunogenic and generates immune response.…”

“…5 SPAG9 has been found to be expressed in 74% of CRC patients and generate humoral response in 70% of CRC patients. 6 Other CT antigens, OY-TES-1, 7 NY-ESO-1, 8 MAGE-A3, 9 and TSP50 10 have also been studied for their role in CRC but in a small number of patients. AKAP4, a new member of CT antigen protein family, is expressed exclusively in male germ cells during spermatogenesis.…”

Screening of a Specific Peptide Binding to VPAC1 Receptor from a Phage Display Peptide Library

“…Cancer cells often display high numbers of certain cell surface molecules, such as tumor-associated antigens or specific receptors, that infrequently occur in normal tissues and represent potential targets for tumor diagnosis and treatment. In our previous study, we first reported that testes-specific protease 50 (TSP50) was abnormally and highly expressed in CRC and represented a potential effective predictor of poor prognosis in CRC patients, making it an attractive novel target for molecular imaging and therapy [30]. Several previous reports demonstrated that the VPAC1 receptor is highly expressed in CRC and plays a major role in the progression of CRC [11], [14], making it one of the most promising novel candidate markers for early CRC detection.…”