Yonsei Med J.  2020 Jan;61(1):15-19. 10.3349/ymj.2020.61.1.15.

Increased Progastrin-Releasing Peptide Expression is Associated with Progression in Gastric Cancer Patients

• Li L
• Yin X
• Meng H
• Hu J
• Yu Z
• Xu J

• KMID: 2466331
• DOI: http://doi.org/10.3349/ymj.2020.61.1.15

Abstract

PURPOSE
The purpose of this study was to assess the diagnostic and prognostic value of serum progastrin-releasing peptide (ProGRP) in patients with gastric cancer (GC).
MATERIALS AND METHODS
A total of 150 patients with GC (89 males and 61 females) were recruited, including those with stage I (n=28), stage II (n=33), stage III (n=50), and stage IV (n=39) disease; 50 healthy controls and 66 patients with benign gastric diseases were also enrolled. Levels of serum ProGRP, carcinoembryonic antigen (CEA), and carbohydrate antigen 72-4 (CA72-4) were measured in all subjects.
RESULTS
Serum ProGRP levels were significantly higher in GC patients than in controls (p<0.001), and ProGRP was significantly correlated with tumor size, tumor node metastasis stage, differentiation, invasion depth, and lymph node metastasis (p< 0.005). ProGRP levels were significantly decreased after chemotherapy (p<0.001). Receiver operating characteristic curves revealed a sensitivity and specificity for serum ProGRP in GC of 85.9% and 81.2%, respectively. ProGRP levels were positively correlated with CA72-4 and CEA (r=0.792 and 0.688, p<0.05, respectively). Combined detection of ProGRP, CEA, and CA72-4 showed the best diagnostic power for GC.
CONCLUSION
ProGRP may be useful as a potential biomarker for GC diagnosis and therapy.

Keyword

Progastrin-releasing peptide; gastric cancer; progression

MeSH Terms

Carcinoembryonic Antigen
Diagnosis
Drug Therapy
Humans
Lymph Nodes
Male
Neoplasm Metastasis
ROC Curve
Sensitivity and Specificity
Stomach Diseases
Stomach Neoplasms*
Carcinoembryonic Antigen

Figure

• 

  Fig. 1 Comparison of serum progastrin-releasing peptide (ProGRP) levels in patients with gastric cancer (GC), patients with benign gastric disease, and healthy controls.

• 

  Fig. 2 Receiver operating characteristic (ROC) curve for serum progastrin-releasing peptide levels in patients with gastric cancer.

• 

  Fig. 3 Serum progastrin-releasing peptide (ProGRP) levels positively correlated with carcinoembryonic antigen (CEA) (A) and carbohydrate antigen 72-4 (CA72-4) (B), respectively, in patients with gastric cancer.

Reference

1. Wang Y, Wang M. Prognostic significance of expression of cysteinerich 61 and cyclooxygenase-2 in gastric cancer. BMC Gastroenterol. 2016; 16:74. PMID: 27457107.

2. Seol SY, Kim C, Lim JY, Yoon SO, Hong SW, Kim JW, et al. Overexpression of endoplasmic reticulum oxidoreductin 1-α (ERO1L) is associated with poor prognosis of gastric cancer. Cancer Res Treat. 2016; 48:1196–1209. PMID: 26987398.

3. Qu Y, Zhou C, Zhang J, Cai Q, Li J, Du T, et al. The metastasis suppressor SOX11 is an independent prognostic factor for improved survival in gastric cancer. Int J Oncol. 2014; 44:1512–1520. PMID: 24604109.

4. Jo MJ, Lee JH, Nam BH, Kook MC, Ryu KW, Choi IJ, et al. Preoperative serum angiopoietin-2 levels correlate with lymph node status in patients with early gastric cancer. Ann Surg Oncol. 2009; 16:2052–2057. PMID: 19408052.

5. Jin C, Lin JR, Ma L, Song Y, Shi YX, Jiang P, et al. Elevated spondin-2 expression correlates with progression and prognosis in gastric cancer. Oncotarget. 2017; 8:10416–10424. PMID: 28060752.

6. Mayer RJ, Venook AP, Schilsky RL. Progress against GI cancer during the American Society of Clinical Oncology’s first 50 years. J Clin Oncol. 2014; 32:1521–1530. PMID: 24752046.

7. Taira N, Kawabata T, Ichi T, Kushi K, Yohena T, Kawasaki H, et al. Utility of the serum ProGRP level for follow-up of pulmonary carcinoid tumors. Am J Case Rep. 2014; 15:337–339. PMID: 25109370.

8. Ischia J, Patel O, Bolton D, Shulkes A, Baldwin GS. Expression and function of gastrin-releasing peptide (GRP) in normal and cancerous urological tissues. BJU Int. 2014; 113 Suppl 2:40–47. PMID: 24894852.

9. Lv SP, Wang Y, Huang L, Wang F, Zhou JG, Ma H. Meta-analysis of serum gastrin-releasing peptide precursor as a biomarker for diagnosis of small cell lung cancer. Asian Pac J Cancer Prev. 2017; 18:391–397. PMID: 28345820.

10. Molina R, Filella X, Augé JM. ProGRP: a new biomarker for small cell lung cancer. Clin Biochem. 2004; 37:505–511. PMID: 15234231.

11. Oh HJ, Park HY, Kim KH, Park CK, Shin HJ, Lim JH, et al. Progastrin-releasing peptide as a diagnostic and therapeutic biomarker of small cell lung cancer. J Thorac Dis. 2016; 8:2530–2537. PMID: 27747005.

12. Molina R, Auge JM, Filella X, Viñolas N, Alicarte J, Domingo JM, et al. Pro-gastrin-releasing peptide (ProGRP) in patients with benign and malignant diseases: comparison with CEA, SCC, CYFRA 21-1 and NSE in patients with lung cancer. Anticancer Res. 2005; 25(3A):1773–1778. PMID: 16033098.

13. Korse CM, Holdenrieder S, Zhi XY, Zhang X, Qiu L, Geistanger A, et al. Multicenter evaluation of a new progastrin-releasing peptide (ProGRP) immunoassay across Europe and China. Clin Chim Acta. 2015; 438:388–395. PMID: 25262909.

14. Edge SB, Compton CC. The American Joint Committee on Cancer: the 7th edition of the AJCC cancer staging manual and the future of TNM. Ann Surg Oncol. 2010; 17:1471–1474. PMID: 20180029.

15. Pan Z, Pang L, Ding B, Yan C, Zhang H, Du L, et al. Gastric cancer staging with dual energy spectral CT imaging. PLoS One. 2013; 8:e53651. PMID: 23424614.

16. Chen XJ, Li N, Huang YD, Ren S, Liu F, Chen L, et al. Factors for postoperative gallstone occurrence in patients with gastric cancer: a meta-analysis. Asian Pac J Cancer Prev. 2014; 15:877–881. PMID: 24568511.

17. Durães C, Almeida GM, Seruca R, Oliveira C, Carneiro F. Biomarkers for gastric cancer: prognostic, predictive or targets of therapy? Virchows Arch. 2014; 464:367–378. PMID: 24487788.

18. Gong Z, Lu R, Xie S, Jiang M, Liu K, Xiao R, et al. Overexpression of pro-gastrin releasing peptide promotes the cell proliferation and progression in small cell lung cancer. Biochem Biophys Res Commun. 2016; 479:312–318. PMID: 27639644.

19. Molina R, Augé JM, Bosch X, Escudero JM, Viñolas N, Marrades R, et al. Usefulness of serum tumor markers, including progastrin-releasing peptide in patients with lung cancer: correlation with histology. Tumour Biol. 2009; 30:121–129. PMID: 19506400.

20. Nakahama H, Tanaka Y, Fujita Y, Fujii M, Sugita M. CYFRA 21-1 and ProGRP, tumor markers of lung cancer, are elevated in chronic renal failure patients. Respirology. 1998; 3:207–210. PMID: 9767622.

21. Inaji H, Komoike Y, Motomura K, Higashiyama M, Ohtsuru M, Funai H, et al. Demonstration and diagnostic significance of pro-gastrin-releasing peptide in medullary thyroid carcinoma. Oncology. 2000; 59:122–125. PMID: 10971170.

22. Molina R, Auge JM, Alicarte J, Filella X, Viñolas N, Ballesta AM. Pro-gastrin-releasing peptide in patients with benign and malignant disease. Tumour Biol. 2004; 25:56–61. PMID: 15192313.

23. Molina R, Bosch X, Auge JM, Filella X, Escudero JM, Molina V, et al. Utility of serum tumor markers as an aid in the differential diagnosis of patients with clinical suspicion of cancer and in patients with cancer of unknown primary site. Tumour Biol. 2012; 33:463–474. PMID: 22161237.

24. Korse CM, Taal BG, Bonfrer JM, Vincent A, van Velthuysen ML, Baas P. An elevated progastrin-releasing peptide level in patients with well-differentiated neuroendocrine tumours indicates a primary tumour in the lung and predicts a shorter survival. Ann Oncol. 2011; 22:2625–2630. PMID: 21415235.

25. Yin LK, Sun XQ, Mou DZ. Value of combined detection of serum CEA, CA72-4, CA19-9 and TSGF in the diagnosis of gastric cancer. Asian Pac J Cancer Prev. 2015; 16:3867–3870. PMID: 25987051.

26. Yu J, Zhang S, Zhao B. Differences and correlation of serum CEA, CA19-9 and CA72-4 in gastric cancer. Mol Clin Oncol. 2016; 4:441–449. PMID: 26998301.

27. Tian SB, Yu JC, Kang WM, Ma ZQ, Ye X, Cao ZJ, et al. Combined detection of CEA, CA 19-9, CA 242 and CA 50 in the diagnosis and prognosis of resectable gastric cancer. Asian Pac J Cancer Prev. 2014; 15:6295–6300. PMID: 25124614.

28. 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; 7:49565–49573. PMID: 27385101.

29. Yang AP, Liu J, Lei HY, Zhang QW, Zhao L, Yang GH. CA72-4 combined with CEA, CA125 and CAl9-9 improves the sensitivity for the early diagnosis of gastric cancer. Clin Chim Acta. 2014; 437:183–186. PMID: 25086284.