Expression levels and diagnostic value of serum GDNF, CEA and CA199 in patients with Colorectal Carcinoma

Serum biomarkers for colorectal cancer diagnosis

  • Jue Wang
  • Lulu Liu
  • Yan Zheng
  • Sai Gu Department of Gastroenterology, the First Affiliated Hospital of Chongqing Medical University
Keywords: GDNF, CEA, CA199, Colorectal carcinoma (CRC), Diagnostic value

Abstract


Background: To investigate the expression levels and diagnostic value of glial cell line-derived neurotrophic factor (GDNF), carcinoembryonic antigen (CEA) and carbohydrate antigen199 (CA199) in patients with colorectal carcinoma (CRC).

Methods. 50 CRC patients at our hospital from Feb. 2020 to Feb. 2021 were chosen as the malignant group, another 50 patients with benign colonic diseases were chosen as the benign group, and 50 healthy people who came to our hospital for physical examination during the same period were considered as the control group. Fasting peripheral venous blood was taken from all research subjects in the morning and tested by a fully-automated electrochemiluminometer to determine the GDNF, CEA and CA199 levels. The sensitivity and specificity of the combined detection of the three indexes for CRC were analyzed, and the ROC curve was plotted to record the area under the curve (AUC).

Results. The malignant group had remarkably higher CEA and CA199 levels (P<0.001) and a lower GDNF level (P<0.001) when compared with the benign and control groups. The sensitivity, specificity, positive predictive value and negative predictive value of the combined detection were 96.0%, 94.0%, 88.9% and 97.9%, respectively. The combined detection had the AUC (95% CI) = 0.950 (0.909-0.991), the standard error of 0.021, and the progressive Sig.b<0.001.

Conclusion. The combined diagnosis of serum GDNF, CEA and CA199 is a reliable method to improve the diagnostic accuracy of CRC, and this strategy can effectively reduce the missed diagnosis rate and has high application value in clinic.

References

1.        Chen H, Zhang J, Zhou H, Zhu Y, Liang Y, Zhu P, et al. UHPLC-HRMS-based serum lipisdomics reveals novel biomarkers to assist in the discrimination between colorectal adenoma and cancer. Front Oncol 2022; 12(934145.


2.        Zhang X, Chen QH, Yang Y, Lin JX, Li YC, Zhong TY, et al. Baseline serum uric acid level is associated with progression-free survival, disease control rate, and safety in postoperative patients with colorectal cancer treated by FOLFOX, FOLFIRI, or XELOX. Front Oncol 2022; 12(918088.


3.        Balogh M, Zhang J, Gaffney CM, Kalakuntla N, Nguyen NT, Trinh RT, et al. Sensory neuron dysfunction in orthotopic mouse models of colon cancer. J Neuroinflamm 2022; 19(1): 204.


4.        Farc O, Berindan-Neagoe I, Zaharie F, Budisan L, Zanoaga O, Cristea V. A role for serum cytokines and cell adhesion molecules in the non-invasive diagnosis of colorectal cancer. Oncol Lett 2022; 24(3): 323.


5.        Wang H, Ji D, Tian H, Gao Z, Song C, Jia J, et al. Predictive value of proteomic markers for advanced rectal cancer with neoadjuvant chemoradiotherapy. Bmc Cancer 2022; 22(1): 868.


6.        Takano Y, Haruki K, Tsukihara S, Ito D, Kanno H, Son K, et al. The impact of low serum cholinesterase levels on survival in patients with colorectal cancer. Int J Colorectal Dis 2022; 37(4): 869-77.


7.        Wang N, Yu Y, Xu B, Zhang M, Li Q, Miao L. Pivotal prognostic and diagnostic role of the long noncoding RNA colon cancerassociated transcript 1 expression in human cancer (Review). Mol Med Rep 2019; 19(2): 771-82.


8.        World Medical Association Declaration of Helsinki: ethical principles for medical research involving human subjects. Jama-J Am Med Assoc 2013; 310(20): 2191-4.


9.        Shibutani M, En W, Okazaki Y, Maeda K, Hirakawa K, Ohira M. A High Postoperative Serum C-reactive Protein Level Has a Negative Impact on Long-term Survival, Regardless of Postoperative Infectious Complications, in Patients Who Undergo Laparoscopic Surgery for Colorectal Cancer. Anticancer Res 2021; 41(3): 1593-8.


10.    Li H, Wang Z, Zhao G, Ma Y, Chen Y, Xue Q, et al. Performance of a MethyLight assay for methylated SFRP2 DNA detection in colorectal cancer tissue and serum. Int J Biol Marker 2019; 34(1): 54-9.


11.    Peltonen R, Hagstrom J, Tervahartiala T, Sorsa T, Haglund C, Isoniemi H. High Expression of MMP-9 in Primary Tumors and High Preoperative MPO in Serum  Predict Improved Prognosis in Colorectal Cancer with Operable Liver Metastases. Oncology-Basel 2021; 99(3): 144-60.


12.    Yu YL, Fan CW, Tseng WK, Chang PH, Kuo HC, Pan YP, et al. Correlation Between the Glasgow Prognostic Score and the Serum Cytokine Profile  in Taiwanese Patients with Colorectal Cancer. Int J Biol Marker 2021; 36(2): 40-9.


13.    Iacuzzo C, Germani P, Troian M, Cipolat MT, Giudici F, Osenda E, et al. Serum carcinoembryonic antigen pre-operative level in colorectal cancer: revisiting risk stratification. Anz J Surg 2021; 91(6): E367-74.


14.    Zhong Y, Zhou Q, Zhang Y, Zhou S, Zhang G, Jiang C, et al. Cell-free DNA as a biomarker for colorectal cancer: a retrospective analysis in  patients before and after surgery. Cell Mol Biol 2020; 66(2): 135-41.


15.    Lu DC, Zhang QF, Li L, Luo XK, Liang B, Lu YH, et al. Methylated Septin9 has moderate diagnostic value in colorectal cancer detection  in Chinese population: a multicenter study. Bmc Gastroenterol 2022; 22(1): 232.


16.    Mohammadi D, Zafari Y, Estaki Z, Mehrabi M, Moghbelinejad S. Evaluation of plasma circ_0006282 as a novel diagnostic biomarker in colorectal  cancer. J Clin Lab Anal 2022; 36(1): e24147.


17.    Locker GY, Hamilton S, Harris J, Jessup JM, Kemeny N, Macdonald JS, et al. ASCO 2006 update of recommendations for the use of tumor markers in  gastrointestinal cancer. J Clin Oncol 2006; 24(33): 5313-27.


18.    Chen CC, Yang SH, Lin JK, Lin TC, Chen WS, Jiang JK, et al. Is it reasonable to add preoperative serum level of CEA and CA19-9 to staging for colorectal cancer? J Surg Res 2005; 124(2): 169-74.


19.    Li S, Zhu L, Cheng X, Wang Q, Feng J, Zhou J. The significance of CO(2) combining power in predicting prognosis of patients with stage II and III colorectal cancer. Biomark Med 2019; 13(13): 1071-80.


20.    Zhong F, Zhang W, Cao Y, Wen Q, Cao Y, Lou B, et al. LncRNA NEAT1 promotes colorectal cancer cell proliferation and migration via  regulating glial cell-derived neurotrophic factor by sponging miR-196a-5p. Acta Bioch Bioph Sin 2018; 50(12): 1190-9.


21.    Chen H, Han T, Gao L, Zhang D. The Involvement of Glial Cell-Derived Neurotrophic Factor in Inflammatory Bowel Disease. J Interf Cytok Res 2022; 42(1): 1-7.


22.    Ashkboos M, Nikbakht M, Zarinfard G, Soleimani M. RET Protein Expression in Colorectal Cancer; An Immunohistochemical Assessment. Asian Pac J Cancer Prev 2021; 22(4): 1019-23.


23.    Dong Z, Dai L, Zhang Y, Fang C, Shi G, Chen Y, et al. Hypomethylation of GDNF family receptor alpha 1 promotes epithelial-mesenchymal  transition and predicts metastasis of colorectal cancer. Plos Genet 2020; 16(11): e1009159.


24.    Huang L, Fang J, Wu J, Zhou X, Wei H. [Prognostic value of combining preoperative serum tumor markers and peripheral  blood routine indexes in patients with colorectal cancer]. Zhonghua Wei Chang Wai Ke Za Zhi 2018; 21(12): 1421-6.


25.    Zeng J, Yu H, Gan HT. Glial cell line-derived neurotrophic factor ameliorates dextran sulfate sodium-induced colitis in mice via a macrophage-mediated pathway. Int Immunopharmacol 2021; 100: 108143.

Published
2023/10/03
Section
Original paper