Clinical significance and diagnostic capacity of serum TK1, CEA, CA 19-9 and CA 72-4 levels in gastric and colorectal cancer patients

Shufang Ning, Wene Wei, Jilin Li, Bingbing Hou, Jianhong Zhong, Yuxuan Xie, Haizhou Liu, Xianwei Mo, Jiansi Chen, Litu Zhang, Shufang Ning, Wene Wei, Jilin Li, Bingbing Hou, Jianhong Zhong, Yuxuan Xie, Haizhou Liu, Xianwei Mo, Jiansi Chen, Litu Zhang

Abstract

Despite extensive progress in treatment for cancer in recent decades, the early diagnosis for gastric cancer (GC) and colorectal cancer (CRC) remains poor. In this study, we explore the diagnostic value of joint detection of thymidine kinase 1 (TK1), carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (CA 19-9) and carbohydrate antigen 72-4 (CA 72-4) in the diagnosis of GC and CRC, and to evaluated the relationship between TK1 expression and clinical pathological characteristics in the patients. Serum TK1, CA 19-9, CA 72-4 and CEA levels were measured in 169 patients with GC, 344 patients with CRC and 75 healthy controls using electro-chemiluminescence. The TK1 concentration was significantly higher in patients with cancer than in healthy controls and patients with clinical stage Ⅲ+Ⅳ had higher TK1 levels than clinical stage Ⅰ+Ⅱ (P<0.05). The levels of TK1 is significantly associated with tumor stage, lymph node metastasis, distant metastasis, tumor differentiation and age (P<0.05). When the tumor markers (TK1, CA 19-9 and CA 72-4) were detected respectively, the area under receiver operating characteristics curve (AUC) of TK1 for three cancers was the highest (0.823-0.895). However, the combination of AUC was higher than that for each tumor marker detected respectively (0.934-0.953), and the Hosmer-Lemeshow test showed an adequate model of calibration (P>0.05). Moreover, the AUCs varied significantly between the combination tests and single biomarker tests (Z test, P<0.01). In conclusion, serum TK1 may be an independent tumor marker for GC and CRC patients, and the combination of TK1, CA 19-9 and CA 72-4 and CEA performed even better. This study suggests that combination detection of four tumor markers may prove to be useful for the diagnosis of GC and CRC.

Keywords: CA 19-9; CA 72-4; CEA.; TK1; colorectal cancer; gastric cancer.

Conflict of interest statement

Competing Interests: The authors have declared that no competing interest exists.

Figures

Figure 1
Figure 1
Positive rate of serum tumor markers in gastric and colorectal cancer according to tumor stage.
Figure 2
Figure 2
Box plot of distribution of TK1 in serum in three cancers (gastric, colon and rectal cancer) and healthy controls. The center line and box represent the median and interquartile ranges, respectively. The values of the maximum and minimum, eliminating outliers, are represented by the vertical lines. *P<0.05.
Figure 3
Figure 3
ROC curves of single TK1, CA 19-9, CA 72-4, CEA and the combination in predicting gastric cancer (A), colon cancer (B) and rectal cancer (C)

References

    1. Stewart BW WC. World cancer report 2014. Lyon: International Agency for Research on Cancer; 2014.
    1. Wang Y, Jiang X, Dong S, Shen J, Yu H, Zhou J. et al. Serum TK1 is a more reliable marker than CEA and AFP for cancer screening in a study of 56,286 people. Cancer Biomark. 2016;16:529–36.
    1. Gasparri F, Wang N, Skog S, Galvani A, Eriksson S. Thymidine kinase 1 expression defines an activated G1 state of the cell cycle as revealed with site-specific antibodies and ArrayScan assays. European journal of cell biology. 2009;88:779–85.
    1. Chen YL, Eriksson S, Chang ZF. Regulation and functional contribution of thymidine kinase 1 in repair of DNA damage. The Journal of biological chemistry. 2010;285:27327–35.
    1. Nisman B, Nechushtan H, Biran H, Gantz-Sorotsky H, Peled N, Gronowitz S. et al. Serum thymidine kinase 1 activity in the prognosis and monitoring of chemotherapy in lung cancer patients: a brief report. Journal of thoracic oncology: official publication of the International Association for the Study of Lung Cancer. 2014;9:1568–72.
    1. Aufderklamm S, Todenhofer T, Gakis G, Kruck S, Hennenlotter J, Stenzl A. et al. Thymidine kinase and cancer monitoring. Cancer letters. 2012;316:6–10.
    1. Chen G, He C, Li L, Lin A, Zheng X, He E. et al. Nuclear TK1 expression is an independent prognostic factor for survival in pre-malignant and malignant lesions of the cervix. BMC cancer. 2013;13:249.
    1. Alegre MM, Weyant MJ, Bennett DT, Yu JA, Ramsden MK, Elnaggar A. et al. Serum detection of thymidine kinase 1 as a means of early detection of lung cancer. Anticancer research. 2014;34:2145–51.
    1. Song S, Hong JC, McDonnell SE, Koong AC, Minsky BD, Chang DT. et al. Combined modality therapy for rectal cancer: the relative value of posttreatment versus pretreatment CEA as a prognostic marker for disease recurrence. Annals of surgical oncology. 2012;19:2471–6.
    1. Tarantino I, Warschkow R, Schmied BM, Guller U, Mieth M, Cerny T. et al. Predictive Value of CEA for Survival in Stage I Rectal Cancer: a Population-Based Propensity Score-Matched Analysis. Journal of gastrointestinal surgery: official journal of the Society for Surgery of the Alimentary Tract. 2016;20:1213–22.
    1. Lin JK, Lin CC, Yang SH, Wang HS, Jiang JK, Lan YT. et al. Early postoperative CEA level is a better prognostic indicator than is preoperative CEA level in predicting prognosis of patients with curable colorectal cancer. International journal of colorectal disease. 2011;26:1135–41.
    1. Chen XZ, Zhang WK, Yang K, Wang LL, Liu J, Wang L. et al. Correlation between serum CA724 and gastric cancer: multiple analyses based on Chinese population. Molecular biology reports. 2012;39:9031–9.
    1. Chen XZ, Zhang WH, Chen HN, Liu JP, He D, Liu Y. et al. Associations between serum CA724 and HER2 overexpression among stage II-III resectable gastric cancer patients: an observational study. Oncotarget. 2016;7:23647–57.
    1. Wang W, Li Y, Zhang X, Jing J, Zhao X, Wang Y. et al. Evaluating the significance of expression of CEA mRNA and levels of CEA and its related proteins in colorectal cancer patients. Journal of surgical oncology. 2014;109:440–4.
    1. Chen W, Zheng R, Baade PD, Zhang S, Zeng H, Bray F. et al. Cancer statistics in China, 2015. CA: a cancer journal for clinicians. 2016;66:115–32.
    1. Jagarlamudi KK, Hansson LO, Eriksson S. Breast and prostate cancer patients differ significantly in their serum Thymidine kinase 1 (TK1) specific activities compared with those hematological malignancies and blood donors: implications of using serum TK1 as a biomarker. BMC cancer. 2015;15:66.
    1. Bolayirli M, Papila C, Korkmaz GG, Papila B, Aydogan F, Karatas A. et al. Serum thymidine kinase 1 activity in solid tumor (breast and colorectal cancer) patients treated with adjuvant chemotherapy. Journal of clinical laboratory analysis. 2013;27:220–6.
    1. Mao Y, Wu J, Skog S, Eriksson S, Zhao Y, Zhou J. et al. Expression of cell proliferating genes in patients with non-small cell lung cancer by immunohistochemistry and cDNA profiling. Oncology reports. 2005;13:837–46.
    1. Liu Y, Ling Y, Qi Q, Tang Y, Xu J, Tong Z. et al. Changes in serum thymidine kinase 1 levels during chemotherapy correlate with objective response in patients with advanced gastric cancer. Experimental and therapeutic medicine. 2011;2:1177–81.
    1. Chen Y, Ying M, Chen Y, Hu M, Lin Y, Chen D. et al. Serum thymidine kinase 1 correlates to clinical stages and clinical reactions and monitors the outcome of therapy of 1,247 cancer patients in routine clinical settings. International journal of clinical oncology. 2010;15:359–68.
    1. Xu Y, Shi QL, Ma H, Zhou H, Lu Z, Yu B. et al. High thymidine kinase 1 (TK1) expression is a predictor of poor survival in patients with pT1 of lung adenocarcinoma. Tumour biology: the journal of the International Society for Oncodevelopmental Biology and Medicine. 2012;33:475–83.
    1. Chen Z, Zhou H, Li S, He E, Hu J, Zhou J. et al. Serological thymidine kinase 1 (STK1) indicates an elevated risk for the development of malignant tumours. Anticancer research. 2008;28:3897–907.
    1. Li H, Zhang B, Hu X, Dong Y, Fan Q, Guo F. et al. Serum Helicobacter pylori FliD antibody and the risk of gastric cancer. Oncotarget. 2016;7:22397–408.
    1. Tsouma A, Aggeli C, Lembessis P, Zografos GN, Korkolis DP, Pectasides D. et al. Multiplex RT-PCR-based detections of CEA, CK20 and EGFR in colorectal cancer patients. World journal of gastroenterology. 2010;16:5965–74.
    1. Liang Y, Wang W, Fang C, Raj SS, Hu WM, Li QW. et al. Clinical significance and diagnostic value of serum CEA, CA19-9 and CA72-4 in patients with gastric cancer. Oncotarget. 2016;7:49565–73.
    1. Wang YF, Feng FL, Zhao XH, Ye ZX, Zeng HP, Li Z. et al. Combined detection tumor markers for diagnosis and prognosis of gallbladder cancer. World journal of gastroenterology. 2014;20:4085–92.
    1. Srivastava K, Srivastava A, Mittal B. Potential biomarkers in gallbladder cancer: present status and future directions. Biomarkers: biochemical indicators of exposure, response, and susceptibility to chemicals. 2013;18:1–9.

Source: PubMed

3
구독하다