Expression and clinical significance of Spondin 2 in gastric cancer
HUANG Bin1 WANG Liping1 LIN Zhenmeng2▲
1.Department of Anesthesiology, No. 900 Hospital of the Joint Logistics Support Force of the Chinese People’s Liberation Army, Fujian Province, Fuzhou 350025, China;
2.Department of Gastrointestinal Surgery, Fujian Cancer Hospital, Fujian Province, Fuzhou 350014, China
Abstract:Obective To detect the expression of Spondin 2 (SPON2) in cell lines, tissues and serums of gastric cancer, and investigate its value in gastric cancer. Methods The expression of SPON2 protein in gastric cancer cell lines BGC-823, MGC-803, SGC-7901 and normal gastric mucosal cells GES-1 were detected. From January 2013 to September 2015, the expression of SPON2 in the paraffins of 120 gastric cancer and corresponding para-carcinoma tissues archived by the Department of Pathology No. 900 Hospital of the Joint Logistics Support Force of the Chinese People’s Liberation Army were detected. The expression levels of SPON2, carcinoembryonic antigen (CEA) and carbohydrate antigen19-9 (Ca19-9) in serums of 70 patients with gastric cancer, 60 patients with chronic atrophic gastritis and 60 healthy subjects were detected from May 2019 to September 2020. Results The expression level of SPON2 in all gastric cancer cell lines was higher than that in normal gastric mucosa cell GES-1 (P < 0.05). The positive rate of SPON2 in gastric cancer tissues was higher than that in adjacent normal tissues (P < 0.05). Multivariate survival analysis showed that SPON2 was an independent risk factor for prognosis of gastric cancer (OR = 0.712, 95%CI: 0.431-0.978, P < 0.05). The relative expression of serum SPON2 in gastric cancer patients was higher than that in chronic atrophic gastritis patients and healthy subjects (P < 0.05). The area under the curve of the combined detection of serum SPON2, CEA and Ca19-9 was significantly different from that of the single detection (P < 0.05). Conclusion SPON2 protein may be involved in the occurrence and development of gastric cancer. Combined detection of serum SPON2, CEA and Ca19-9 is beneficial to improve the diagnosis of gastric cancer.
[1] Kahvecioglu S,Ersoy A,?譈stundag Y,et al. The Comparison Spondin 2 Levels in Primary Glomerular Diseases [J]. Saudi J Kidney Dis Transpl,2020,31(5):1014-1024.
[2] Yan L,Wei X,Tang QZ,et al. Cardiac-specific mindin overexpression attenuates cardiac hypertrophy via blocking AKT/GSK3β and TGF-β1-Smad signaling [J]. Cardiovasc Res,2011,92:85-94.
[3] Li N,Liu S,Zhang Y,et al. Transcriptional Activation of Matricellular Protein Spondin2 (SPON2) by BRG1 in Vascular Endothelial Cells Promotes Macrophage Chemotaxis [J]. Front Cell Dev Biol,2020,8:794.
[4] Feng Y,Hu Y,Mao Q,et al. Upregulation of Spondin-2 protein expression correlates with poor prognosis in hepatocellular carcinoma [J]. J Int Med Res,2019,47(2):569-579.
[5] Ma HM,Yu M,Wu C,et al. Overexpression of Spondin-2 Is Associated with Recurrence-Free Survival in Patients with Localized Clear Cell Renal Cell Carcinoma [J]. Dis Markers,2020,2020:5074239.
[6] ?譕lajpah M,Hauptman N,Bo?觢tjan■i■ E,et al. Differential expression of extracellular matrix-related genes DCN,EPHA4,FN1,SPARC,SPON2 and SPP1 in colorectal carcinogenesis [J]. Oncol Rep,2019,42(4):1539-1548.
[7] Ben Brahim E,Ayari I,Jouini R,et al. Expression of epidermal growth factor receptor (EGFR) in colorectal cancer:An immunohistochemical study [J]. Arab J Gastroenterol,2018,19(3):121-124.
[8] Siegel RL,Miller KD,Jemal A. Cancer statistics,2019 [J]. CA Cancer J Clin,2019,69:7-34.
[9] Allemani C,Weir HK,Carreira H,et al. Global surveillance of cancer survival 1995-2009:analysis of individual data for 25,676,887 patients from 279 population -based registries in 67 countries [J]. Lancet,2015,385:977-1010.
[10] 韩博涵,吕慧芳,陈小兵.胃癌腹膜转移治疗的研究进展[J].中国医药导,2020,17(4):28-31.
[11] Bray C,Bell LN,Liang H,et al. Colorectal Cancer Screen ing [J]. WMJ,2017,116:27-33.
[12] Wang J,Sun Y,Bertagnolli MM,et al. Comparison of gastric cancer survival between Caucasian and Asian patients treated in the United States:results from the Surveillance Epidemiology and End Results (SEER) database [J]. Annals of Surgical Oncology,2015,22(9):2965-2971.
[13] Bosch X,Molina R,Marrades R,et al. Tumor markers with clinically controlled cutoffs for suspected cancer [J]. Eur J Clin Invest,2021,16,e13523.
[14] Zhu SY,Ji M. Standardized endoscope diagnosis and treatment of early gastric cancer [J]. Zhonghua Nei Ke Za Zhi,2020,59(3):236-239.
[15] Sorensen CG,Karlsson WK,Pommergaard HC,et al. The diagnostic accuracy of carcinoembryonic antigen to detect colorectal cancer recurrence a systematic review [J]. Int J Surg,2016,25:134-144.
[16] Zhou YC,Zhao HJ,Shen LZ. Preoperative serum CEA and CA19-9 in gastric cancer—a single tertiary hospital study of 1,075 cases [J]. Asian Pac J Cancer Prev,2015, 16 (7):2685-2691.
[17] Wu L,Zhang W,Qian J,et al. R-spondin family members as novel biomarkers and prognostic factors in lung cancer [J]. Oncol Lett,2019,18(4):4008-4015.
[18] Xu Z,Yu Z,Nai S,et al. Structure-based design of competitive ligands to target Spon2 in gastric cancer: An integration of molecular modeling and in vitro assay [J]. Bioorg Chem,2017,74:115-121.
[19] Zhang YL,Li Q,Yang XM,et al. SPON2 Promotes M1-like Macrophage Recruitment and Inhibits Hepatocellular Carcinoma Metastasis by Distinct Integrin-Rho GTPase-Hippo Pathways [J]. Cancer Res,2018,78(9):2305-2317.
[20] Zhu BP,Guo ZQ,Lin L,et al. Serum BSP,PSADT,and Spondin-2 levels in prostate cancer and the diagnostic significance of their ROC curves in bone metastasis [J]. Eur Rev Med Pharmacol Sci,2017,21(1):61-67.
[21] Yuan X,Bian T,Liu J,et al. Spondin2 is a new prognostic biomarker for lung adenocarcinoma [J]. Oncotarget,2017,8(35):59324-59332.
[22] Ni H,Ni T,Feng J,et al. Spondin-2 is a novel diagnostic biomarker for laryngeal squamous cell carcinoma [J]. Pathol Res Pract,2019,215(2):286-291.
[23] Chandrasinghe P,Stebbing J,Warusavitarne J,et al. The MACC1-SPON2 axis: a new biomarker and therapeutic target in colorectal cancer [J]. Oncogene,2017,36(11):1474-1475.
[24] Schmid F,Wang Q,Huska MR,et al. SPON2,a newly identified target gene of MACC1,drives colorectal cancer metastasis in mice and is prognostic for colorectal cancer patient survival [J]. Oncogene,2016,35(46):5942-5952.
[25] Lu H,Feng Y,Hu Y,et al. Spondin 2 promotes the proliferation,migration and invasion of gastric cancer cells [J]. J Cell Mol Med,2020,24(1):98-113.
[26] Kang HG,Kim WJ,Noh MG,et al. SPON2 Is Upregulated through Notch Signaling Pathway and Promotes Tumor Progression in Gastric Cancer [J]. Cancers(Basel),2020, 12(6):1439.