Document Type : Original Article

Authors

1 Department of Critical Care Medicine, Huadu District People's Hospital, Southern Medical University, 48 Xinhua Road, Huadu, Guangzhou, Guangdong 510800, P.R. China.

2 Department of Central Laboratory, Huadu District People's Hospital, Southern Medical University, 22 Baohua Road, Huadu, Guangzhou, Guangdong 510800, P.R. China.

3 Department of General Surgery, Huadu District People's Hospital, Southern Medical University, 48 Xinhua Road, Huadu, Guangzhou, Guangdong 510800, P.R. China.

Abstract

Background: Suppressor APC domain containing 2 (SAPCD2) is involved in cell cycle regulation and its mRNA levels are higher in cancer tissues. But, the function of SAPCD2 in cancer development remains unclear.
Objective: To generate mouse monoclonal antibodies (mAbs) specific to SAPCD2 and thus clarify the function of SAPCD2 in the development of gastric carcinoma (GC).
Methods: Purified SAPCD2-GST immunized BALB/c mouse spleen cells were collected and fused with myeloma cells to obtain monoclonal antibody hybridoma. A group of monoclonal antibodies exhibiting high specificity and sensitivity against SAPCD2 has been generated and characterized by IHC, WB, IP, IF, and ELISA. By immunohistochemical analysis, the SAPCD2 expression was evaluated in 228 clinical samples of gastric mucosal lesions, including precancerous lesions and GC samples.
Results: We identified a highly specific and sensitive clone of s12 in eukaryotic cells and performed an IHC analysis. We found that 81.3% of 107 GC tissues were SAPCD2-positive, compared with the 26.2% in the matched adjacent normal-appearing tissues (P<0.001). Furthermore, among the 121 gastritis tissues, SAPCD2 was overexpressed in precancerous gastric lesions such as dysplasia (Dys, 78.9%), intestinal metaplasia (IM, 44.7%), and chronic atrophic gastritis (CAG, 6.1%) compared with that in chronic non-atrophic gastritis (CNAG, 3.2%) (P<0.001). The SAPCD2-positivity rate was 81.3% in GC, suggesting that the expression of SAPCD2 increased with the severity of the lesion (P<0.001).
Conclusion: In summary, we have described novel monoclonal antibodies against SAPCD2, which are highly expressed in GC tissues and may serve as the basis for an early clinical marker for GC development.

Keywords

  1. Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018;68(6):394-424.
  2. Casamayor M, Morlock R, Maeda H, Ajani J. Targeted literature review of the global burden of gastric cancer. Ecancermedicalscience. 2018;12:883.
  3. Warsinggih, Syarifuddin E, Marhamah, Lusikooy RE, Labeda I, Sampetoding S, et al. Association of clinicopathological features and gastric cancer incidence in a single institution. ASIAN J SURG. 2022;45(1):246-9.
  4. Gullo I, Grillo F, Mastracci L, Vanoli A, Carneiro F, Saragoni L, et al. Precancerous lesions of the stomach, gastric cancer and hereditary gastric cancer syndromes. Pathologica. 2020;112(3):166-85.
  5. Zheng RS, Sun KX, Zhang SW, Zeng HM, Zou XN, Chen R, et al. [Report of cancer epidemiology in China, 2015]. Zhonghua Zhong Liu Za Zhi. 2019;41(1):19-28.
  6. Russo AE, Strong VE. Gastric Cancer Etiology and Management in Asia and the West. ANNU REV MED. 2019;70(1):353-67.
  7. Ang TL, Fock KM, Tan MT, Assam PN, Chan ES. Impact of Asia-Pacific guidelines on gastric cancer and Helicobacter pylori infection on prevailing clinical practices. J Dig Dis. 2016;17(2):122-7.
  8. Rawla P, Barsouk A. Epidemiology of gastric cancer: global trends, risk factors and prevention. Prz Gastroenterol. 2019;14(1):26-38.
  9. Yakirevich E, Resnick MB. Pathology of gastric cancer and its precursor lesions. Gastroenterol Clin North Am. 2013;42(2):261-84.
  10. Kim GH, Liang PS, Bang SJ, Hwang JH. Screening and surveillance for gastric cancer in the United States: Is it needed? GASTROINTEST ENDOSC. 2016;84(1):18-28.
  11. Compare D, Rocco A, Nardone G. Screening for and surveillance of gastric cancer. World J Gastroenterol. 2014;20(38):13681-91.
  12. Lansdorp-Vogelaar I, Kuipers EJ. Screening for gastric cancer in Western countries. GUT. 2016;65(4):543-4.
  13. Xu X, Li W, Fan X, Liang Y, Zhao M, Zhang J, et al. Identification and characterization of a novel p42.3 gene as tumor-specific and mitosis phase-dependent expression in gastric cancer. ONCOGENE. 2007;26(52):7371-9.
  14. Zhang ZM, Cao HB, Li ZH, Zhuo R, Tao YF, Li XL, et al. SAPCD2 promotes neuroblastoma progression by altering the subcellular distribution of E2F7. CELL DEATH DIS. 2022;13(2):174.
  15. Luo Y, Wang L, Ran W, Li G, Xiao Y, Wang X, et al. Overexpression of SAPCD2 correlates with proliferation and invasion of colorectal carcinoma cells. CANCER CELL INT. 2020;20(1):43.
  16. Jung Y, Lee S, Choi HS, Kim SN, Lee E, Shin Y, et al. Clinical validation of colorectal cancer biomarkers identified from bioinformatics analysis of public expression data. CLIN CANCER RES. 2011;17(4):700-9.
  17. Kohler G, Milstein C. Derivation of specific antibody-producing tissue culture and tumor lines by cell fusion. EUR J IMMUNOL. 1976;6(7):511-9.
  18. Fransolet M, Henry L, Labied S, Masereel MC, Blacher S, Noel A, et al. Influence of mouse strain on ovarian tissue recovery after engraftment with angiogenic factor. J OVARIAN RES. 2015;8(1):14.
  19. Sun W, Dong WW, Mao LL, Li WM, Cui JT, Xing R, et al. Overexpression of p42.3 promotes cell growth and tumorigenicity in hepatocellular carcinoma. World J Gastroenterol. 2013;19(19):2913-20.
  20. Mao L, Sun W, Li W, Cui J, Zhang J, Xing R, et al. Cell cycle-dependent expression of p42.3 promotes mitotic progression in malignant transformed cells. Mol Carcinog. 2014;53(5):337-48.
  21. Hutchins JR, Toyoda Y, Hegemann B, Poser I, Heriche JK, Sykora MM, et al. Systematic analysis of human protein complexes identifies chromosome segregation proteins. SCIENCE. 2010;328(5978):593-9.
  22. Yan X, Habedanck R, Nigg EA. A complex of two centrosomal proteins, CAP350 and FOP, cooperates with EB1 in microtubule anchoring. MOL BIOL CELL. 2006;17(2):634-44.
  23. Le Clech M. Role of CAP350 in centriolar tubule stability and centriole assembly. PLOS ONE. 2008;3(12):e3855.