成纤维细胞生长因子结合蛋白2过表达促进食管癌细胞的增殖

doi:10.3969/j.issn.1004-616x.2019.03.002

Abstract

Abstract: OBJECTIVE: This study aimed to detect the expression of human fibroblast growth factor binding protein 2 (FGFBP2) mRNA and to explore its prognostic value in esophageal squamous cell carcinoma (ESCC). METHODS:Tissue microarrays and RNA in situ hybridization (RISH) were used to detect expression of FGFBP2 mRNA in 190 cases of ESCC tissues and 42 cases of adjacent normal tissues. Proliferation assays were utilized to explore the roles of FGFBP2 in ESCC cells in vitro. RESULTS:RISH results show positive expression of FGFBP2 mRNA in 49 out 190 (25.8%) ESCC tissues,whereas no FGFBP2 mRNA signal was detected in normal surgical margins tissues (P<0.01). High expression of FGFBP2 mRNA was correlated with shorter survival time of ESCC patients (P=0.002). Cox regression analyses indicate that FGFBP2 mRNA was an independent prognostic factor in ESCC patients (HR:2.291,95%CI:1.271-4.129,P=0.006). Knockdown of FGFBP2 inhibited the proliferation of ESCC cell lines KYSE150 and KYSE510. Western blotting results demonstrate that knockdown of FGFBP2 decreased the level of phosphorylated AKT (p-AKT) but did not affect the expression of phosphorylated ERK (p-ERK) protein. CONCLUSION: Our data suggest that FGFBP2 mRNA may be a prognosis biomarker of ESCC. With respect to the mechanism, our studies show that knockdown of FGFBP2 depressed proliferation of ESCC cells through activating the AKT pathway.

Key words: esophageal squamous cell carcinoma, FGFBP2, prognostic biomarker, proliferation

CLC Number:

R735.1

SUN Xiaonan, YUAN Qing, YANG Liyan, ZHANG Yu, CAI Yan, XU Xin, WANG Mingrong, HAO Jiajie, JIA Xuemei. FGFBP2 over-expresssion promoted cell proliferation in esophageal squamous carcinoma cells[J]. Carcinogenesis, Teratogenesis & Mutagenesis, 2019, 31(3): 180-185,192.

References

[1] TRAN G D,SUN X D,ABNET C C,et al. Prospective study of risk factors for esophageal and gastric cancers in the Linxian general population trial cohort in China[J]. Int J Cancer,2005,113(3):456-463.
[2] SONG P I, LIANG H, FAN J H, et al. Long-term survival after esophagectomy for early esophageal squamous cell carcinoma in Linxian,China[J]. J Surg Oncol,2011, 104(2):176-180.
[3] CHEN W,SUN K,ZHENG R,et al. Cancer incidence and mortality in China, 2014[J]. Chin J Cancer Res, 2018,30(1):1-12.
[4] KE L. Mortality and incidence trends from esophagus cancer in selected geographic areas of China circa 1970-90[J]. Int J Cancer,2002,102(3):271-274.
[5] ENZINGER P C, MAYER R J. Esophageal cancer[J]. N Engl J Med,2003,349(23):2241-2252.
[6] HE Y F, LUO H Q, WANG W, et al. Preoperative NLR and PLR in the middle or lower ESCC patients with radical operation[J]. Eur J Cancer Care (Engl), 2017,26(2):e12445.
[7] PENNATHUR A, GIBSON M K, JOBE B A, et al. Oesophageal carcinoma[J]. Lancet,2013,381(9864):400-412.
[8] OGAWA K, TANAKA K, ISHⅡ A, et al. A novel serum protein that is selectively produced by cytotoxic lymphocytes[J]. J Immunol,2001,166(10):6404-6412.
[9] KUEPPER M,KOESTER K,BRATKE K,et al. Increase in Ksp37-positive peripheral blood lymphocytes in mild extrinsic asthma[J]. Clin Exp Immunol, 2004, 137(2):359-365.
[10] CZUBAYKO F, LIAUDET-COOPMAN E D, AIGNER A, et al. A secreted FGF-binding protein can serve as the angiogenic switch in human cancer[J]. Nat Med, 1997,3(10):1137-1140.
[11] YAMANAKA R, ARAO T, YAJIMA N, et al. Identification of expressed genes characterizing long-term survival in malignant glioma patients[J]. Oncogene,2006, 25(44):5994-6002.
[12] JIANG Y Y,SHANG L,SHI Z Z,et al. Microtubuleassociated protein 4 is an important regulator of cell invasion/migration and a potential therapeutic target in esophageal squamous cell carcinoma[J]. Oncogene, 2016, 35(37):4846-4856.
[13] MA S, LU C C, YANG L Y, et al. ANXA2 promotes esophageal cancer progression by activating MYC-HIF1AVEGF axis[J]. J Exp Clin Cancer Res,2018,37(1):1-13.
[14] CAO T, SHEN J, PAN W, et al. Upregulation of long noncoding RNA ANRIL correlates with tumor progression and poor prognosis in esophageal squamous cell carcinoma[J]. J Buon,2018,23(6):1862-1866.
[15] LIN Y, DONG H, DENG W, et al. Evaluation of salivary exosomal chimeric GOLM1-NAA35 RNA as a potential biomarker in esophageal carcinoma[J/OL]. Clin Cancer Res,2019. doi:10.1158/1078-0432.CCR-18-3169.
[16] LIU Y, LI K, REN Z, et al. Clinical implication of elevated human cervical cancer oncogene-1 expression in esophageal squamous cell carcinoma[J]. J Histochem Cytochem,2012,60(7):512-520.
[17] WANG F,XUAN X Y,YANG X,et al. Stathmin is a marker of progression and poor prognosis in esophageal carcinoma[J]. Asian Pac J Cancer Prev, 2014, 15(8):3613-3618.
[18] WANG F, FLANAGAN J, SU N, et al. RNAscope:a novel in situ RNA analysis platform for formalin-fixed, paraffin-embedded tissues[J]. J Mol Diagn, 2012, 14(1):22-29.
[19] ANDERSON C M,ZHANG B,MILLER M,et al. Fully automated RNAscope in situ hybridization assays for formalin-fixed paraffin-embedded cells and tissues[J]. J Cell Biochem,2016,117(10):2201-2208.
[20] WANG Z, PORTIER B P, GRUVER A M, et al. Automated quantitative RNA in situ hybridization for resolution of equivocal and heterogeneous ERBB2(HER2) status in invasive breast carcinoma[J]. J Mol Diagn, 2013,15(2):210-219.
[21] SCHALPER K A,VELCHETI V,CARVAJAL D,et al. In situ tumor PD-L1 mRNA expression is associated with increased TILs and better outcome in breast carcinomas[J]. Clin Cancer Res,2014,20(10):2773-2782.
[22] SJÖBERG E, AUGSTEN M, BERGH J, et al. Expression of the chemokine CXCL14 in the tumour stroma is an independent marker of survival in breast cancer[J]. Br J Cancer,2016,114(10):1117-1124.
[23] SON S M, HA S Y, YOO H Y, et al. Prognostic impact of MYC protein expression in central nervous system diffuse large B-cell lymphoma:comparison with MYC rearrangement and MYC mRNA expression[J]. Mod Pathol,2017,30(1):4-14.
[24] REN X,WU H,LU J,et al. PD1 protein expression in tumor infiltrated lymphocytes rather than PDL1 in tumor cells predicts survival in triple-negative breast cancer[J]. Cancer Biol Ther,2018,19(5):373-380.
[25] DU Q, YAN W, BURTON V H, et al. Validation of esophageal squamous cell carcinoma candidate genes from high-throughput transcriptomic studies[J]. Am J Cancer Res,2013,3(4):402-410.
[26] FEITELSON M A, ARZUMANYAN A, KULATHINAL R J, et al. Sustained proliferation in cancer:mechanisms and novel therapeutic targets[J]. Semin Cancer Biol, 2015,35(Sup):25-54.
[27] ADLUNG L, KAR S, WAGNER M C, et al. Protein abundance of AKT and ERK pathway components governs cell type-specific regulation of proliferation[J]. Mol Syst Biol,2017,13(1):904-928.
[28] MANNING B D, TOKER A. AKT/PKB signaling:navigating the network[J]. Cell,2017,169(3):381-405.

FGFBP2 over-expresssion promoted cell proliferation in esophageal squamous carcinoma cells

PDF (PC)

Knowledge

Abstract

Cite this article

share this article

References

Related Articles 15

Recommended Articles

Metrics

Comments

[1]	ZHAO Yan, SUN Zhenxiao. Metformin inhibitd proliferation and migration of human breast cancer cell in vitro [J]. Carcinogenesis, Teratogenesis & Mutagenesis, 2022, 34(1): 35-39.
[2]	WANG Xiaozhou, LI Hongshi, YU Xi, WEI Ning, WANG Ziying, HE Lijie. Effects of sinomenine on proliferation and invasion of HPV-positive cervical cancer SiHa cells [J]. Carcinogenesis, Teratogenesis & Mutagenesis, 2021, 33(6): 442-445.
[3]	YANG Xingxiao, ZHANG Xueyuan, ZOU Naiyi, SHAN Bao'en, MA Ming, ZHU Shuchai. Effects of HMGB1 silencing on migration, invasion and radiosensitivity of esophageal squamous cell carcinoma cells [J]. Carcinogenesis, Teratogenesis & Mutagenesis, 2021, 33(5): 327-333.
[4]	YANG Liyan, LIU Zou, HAO Jiajie, ZHANG Yu, WANG Mingrong. Study on the mechanism of nucleo-plasma translocation of p62 protein in esophageal squamous cell carcinoma [J]. Carcinogenesis, Teratogenesis & Mutagenesis, 2021, 33(5): 338-344.
[5]	CHANG Chen, YANG Liyan, CAI Hongqing, YUAN Qing, HAO Jiajie, WANG Mingrong. Expressions and clinical implications of SERPINE1 mRNA in esophageal squamous carcinoma tissues [J]. Carcinogenesis, Teratogenesis & Mutagenesis, 2021, 33(4): 245-249.
[6]	HUANG Xiaohua, NIU Yongdong, SHI Ganggang. Inhibitory effects and mechanisms of nuclear receptor FXR activation in cervical cancer cell line CaSki [J]. Carcinogenesis, Teratogenesis & Mutagenesis, 2021, 33(4): 302-306.
[7]	ZHENG Junwen, CHANG Chen, HAO Jiajie, CAI Yan, WANG Mingrong, ZHANG Yu. Investigation on expression and function of NEDD4 in esophageal squamous cell carcinoma [J]. Carcinogenesis, Teratogenesis & Mutagenesis, 2021, 33(3): 203-207,224.
[8]	JIAO Wenjing, GUO Xiujuan, SHAO Junguo, JIAO Wenpeng, ZHANG Jinyan. Relationships among blood cell ratios, clinicopathological characteristics and prognosis in esophageal squamous cell carcinoma [J]. Carcinogenesis, Teratogenesis & Mutagenesis, 2021, 33(3): 213-217.
[9]	ZHANG Die, LIU Xianghe, HUO Miaomiao, LIU Mei, XU Ningzhi, ZHU Hongxia. Effects of miR-195-5p on radiosensitivity of esophageal squamous cell carcinoma cells [J]. Carcinogenesis, Teratogenesis & Mutagenesis, 2021, 33(2): 81-88,94.
[10]	ZHANG Na, FAN Zhilu, YANG Liyan, CHANG Chen, CAI Yan, HAO Jiajie, WANG Mingrong. Clinical significance of decreased SERPINB5 expression in esophageal squamous cell carcinomas [J]. Carcinogenesis, Teratogenesis & Mutagenesis, 2021, 33(2): 101-109.
[11]	FANG Lei, YANG Tao, SHENG Lei, MUTALIFU·Aimaiti, QI Xinxin, AINIWAER·Aikemu, YILIYAER·Nijiati. Biological effects of saponins from the seeds of Nigella glandulifera Freyn on human cervical cancer SiHa cells [J]. Carcinogenesis, Teratogenesis & Mutagenesis, 2021, 33(2): 143-148,152.
[12]	LAN Li, CHEN Haili, XU Lei. Mechanism of RBMS3-S3 on the proliferation, apoptosis and invasion of cervical cancer cells [J]. Carcinogenesis, Teratogenesis & Mutagenesis, 2020, 32(6): 438-443.
[13]	LIN Kaihuang, CAI Gaoyang, LIU Xincheng. Effect of mTOR inhibitor AZD2014 on proliferation of hepatoma HCC cells [J]. Carcinogenesis, Teratogenesis & Mutagenesis, 2020, 32(6): 448-451.
[14]	LIU Peng, BAI Yixiao. Effect of miR-29a on proliferation and migration of human gastric cancer cells [J]. Carcinogenesis, Teratogenesis & Mutagenesis, 2020, 32(6): 452-456,463.
[15]	CHEN Qi, ZHONG Qian, YUE Wentao. Inhibition of nasopharyngeal carcinoma proliferation by RBM24 via regulation of HOTAIR [J]. Carcinogenesis, Teratogenesis & Mutagenesis, 2020, 32(4): 275-280.