Expression level and clinical significance of SFRP4 in esophageal squamous cell carcinoma#br#
HUANG Bin1 WANG Liping1 LIN Baoquan2
1.Department of Anesthesiology, the 900th Hospital of the Joint Logistics Team, Fujian Province, Fuzhou 350025, China;
2.Department of Cardiothoracic Surgery, the 900th Hospital of the Joint Logistics Team, Fujian Province, Fuzhou 350025, China
Abstract：Objective To observe the expression of secreted frizzled-related protein 4 (SFRP4) in esophageal squamous cell carcinoma (ESCC) cell lines, serums and tissues, and to discuess its clinical value. Methods The expression of SFRP4 in esophageal squamous cell line HET-1A and ESCC cell line were compared. The serum samples from 70 ESCC patients, 70 Barrett’s esophagus patients and 70 healthy subjects were collected in the 900th Hospital of the Joint Logistics Team (hereinafter referred to as “our hospital”) from June 2019 to October 2020, and the expression levels of SFRP4, carcinoembryonic antigen (CEA), and squamous cell carcinoma antigen (SCCA) in serum were detected. A total of 160 ESCC and paracancer paraffin tissue specimens were collected from the Department of Pathology in our hospital from March 2013 to April 2015 to detect the expression of SFRP4. Results The expression of SFRP4 in all ESCC cell lines were higher than that in esophageal squamous cell lines (P ＜ 0.05). The expression level of SFRP4 in the serum of ESCC patients was higher than that of Barrett’s esophagus and healthy subjects (P ＜ 0.05). The area under the curve of combined detection with SFRP4, CEA, and SCCA were all higher than that of the single test (P ＜ 0.05). The positive rate of SFRP4 in ESCC was 46.9% in paraffin tissue specimens, which was higher than 15.6% in normal adjacent tissues (P ＜ 0.05). The positive expression of SFRP4 was related to the pathological staging (P ＜ 0.05). Conclusion The SFRP4 could be used as an indicator for auxiliary diagnosis of ESCC, and might become a potential molecular marker for targeted therapy.
[1] He Y，Li D，Shan B，et al. Incidence and mortality of esophagus cancer in China，2008—2012 [J]. Chin J Cancer Res，2019，31（3）：426-434.
[2] Thrumurthy SG，Chaudry MA，Thrumurthy SSD，et al. Oesophageal cancer：risks，prevention，and diagnosis [J]. BMJ，2019，366：14373.
[3] Nfonsam LE，Jandova J，Jecius HC，et al. SFRP4 expression correlates with epithelial mesenchymal transition-linked genes and poor overall survival in colon cancer patients [J]. World J Gastrointest Oncol，2019，11（8）：589-598.
[4] Gay D，Ghinatti G，Guerrero-Juarez CF，et al. Phagocytosis of Wnt inhibitor SFRP4 by late wound macrophages drives chronic Wnt activity for fibrotic skin healing [J]. Sci Adv，2020，6（12）：3704.
[5] Sandsmark E，Andersen MK，Bofin AM，et al. SFRP4 gene expression is increased in aggressive prostate cancer [J]. Sci Rep，2017，7（1）：14276.
[6] Bernreuther C，Daghigh F，M?觟ller K，et al. Secreted Frizzled-Related Protein 4 （SFRP4） is an independent prognostic marker in prostate cancers lacking TMPRSS2：ERG fusions [J]. Pathol Oncol Res，2020，26（4）：2709-2722.
[7] Zheng RS，Sun KX，Zhang SW，et al. Report of cancer epidemiology in China，2015 [J]. Zhonghua Zhong Liu Za Zhi，2019，41（1）：19-28.
[8] Miller KD，Nogueira L，Mariotto AB，et al. Cancer treatment and survivorship statistics，2019 [J]. CA Cancer J Clin，2019，69：363-385.
[9] Peng C，Cohen DJ. Advances in the pharmacotherapeutic management of esophageal squamous cell carcinoma [J]. Expert Opin Pharmacother，2021，22（1）：93-107.
[10] Azbazdar Y，Karabicici M，Erdal E，et al. Regulation of wnt signaling pathways at the plasma membrane and their misregulation in cancer [J]. Front Cell Dev Biol，2021，9：631623.
[11] Zhang Y，Wang X. Targeting the Wnt/β-catenin signaling pathway in cancer [J]. J Hematol Oncol，2020，13（1）：165.
[12] Bicer M，Alarslan P，Guler A，et al. Elevated circulating levels of secreted frizzled-related protein 4 in relation to insulin resistance and androgens in women with polycystic ovary syndrome [J]. J Endocrinol Invest，2020，43（3）：305-313.
[13] Perumal V，Krishnan K，Gratton E，et al. Number and brightness analysis of sFRP4 domains in live cells demonstrates vesicle association signal of the NLD domain and dynamic intracellular responses to Wnt3a [J]. Int J Biochem Cell Biol，2015，64：91-96.
[14] Bhuvanalakshmi G，Gamit N，Patil M，et al. Stemness，Pluripotentiality，and Wnt Antagonism：sFRP4，a Wnt antagonist Mediates Pluripotency and Stemness in Glioblastoma [J]. Cancers （Basel），2018，11（1）：25.
[15] Pawar NM，Rao P. Secreted frizzled related protein 4 （sFRP4） update：A brief review [J]. Cell Signal，2018， 45：63-70.
[16] Zeng W，Cao Y，Jiang W，et al. Knockdown of Sfrp4 attenuates apoptosis to protect against myocardial ischemia/reperfusion injury [J]. J Pharmacol Sci，2019，140（1）：14-19.
[17] H?觟rbelt T，Knebel B，Fahlbusch P，et al. The adipokine sFRP4 induces insulin resistance and lipogenesis in the liver [J]. Biochim Biophys Acta Mol Basis Dis，2019， 1865（10）：2671-2684.
[18] Xu C，Zeng XH，Wang L，et al. sFRP-4，a potential novel serum marker for chronic hepatitis B-related hepatocellular carcinoma [J]. Hepatobiliary Pancreat Dis Int，2015，14（2）：164-170.
[19] Busuttil RA，George J，House CM，et al. SFRP4 drives invasion in gastric cancer and is an early predictor of recurrence [J]. Gastric Cancer，2021，24（3）：589-601.
[20] Yang MW，Tao LY，Yang JY，et al. SFRP4 is a prognostic marker and correlated with Treg cell infiltration in pancreatic ductal adenocarcinoma [J]. Am J Cancer Res，2019，9（2）：363-377.
[21] Eskander RN，Ali S，Dellinger T，et al. Expression patterns of the Wnt pathway inhibitors Dickkopf3 and secreted Frizzled-Related Proteins 1 and 4 in endometrial endometrioid adenocarcinoma：an NRG oncology/Gynecologic oncology group study [J]. Int J Gynecol Cancer，2016，26（1）：125-132.
[22] Mei X，Zhu X，Zuo L，et al. Predictive significance of CYFRA21-1，squamous cell carcinoma antigen and carcinoembryonic antigen for lymph node metastasis in patients with esophageal squamous cancer [J]. Int J Biol Markers，2019，34（2）：200-204.
[23] Sugimura K，Miyata H，Motoori M，et al. The significance of SCC and CEA mRNA in the pleural cavity after lymphadenectomy in esophageal cancer patients who underwent preoperative treatment [J]. World J Surg，2018，42（3）：749-757.
[24] Zheng Q，Zhang L，Tu M，et al. Development of a panel of autoantibody against NSG1 with CEA，CYFRA21-1，and SCC-Ag for the diagnosis of esophageal squamous cell carcinoma [J]. Clin Chim Acta，2021，520（6）：126-132.
[25] Yang D，Wang J，Zhang L，et al. Serum SCCA levels in patients suffering cancers or other diseases [J]. Prog Mol Biol Transl Sci，2019，162：165-175.
[26] Chen H，Tian L，Chen J，et al. Evaluation of 2 commercially systems for detection of serum squamous cell carcinoma antigen in pan squamous cell carcinoma [J]. Cancer Control，2020，27（1）：107.
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