Merve BAŞAR, Melike ÖZÇELİK, Nagehan Özdemir BARIŞIK, Mehmet ALİUSTAOĞLU, Hatice ODABAŞ, Serhat ÖZÇELİK, Selver IŞIK, Sevinç KESER, Özlem ERCELEP, Abdilkerim OYMAN

PTK-7 Expression in Gastric Cancer: A Prognostic Determinant

Background: Protein tyrosine kinase-7, a regulatory protein in the Wnt signaling pathway, was highly overexpressed in various cancer types and assumed to be related to prognosis.Aims: The purpose of this study is to assess whether protein tyrosine kinase-7 expression status in curatively resected gastric carcinoma would independently identify patients with a high risk of recurrence and death.Study Design: Retrospective cohort study.Methods: We included patients who were at least 18 years of age and diagnosed with gastric cancer. The exclusion criterion was a metastatic disease at the time of diagnosis or operation. Data on clinicopathological prognostic determinants and clinical courses, including the date of disease relapse and survival status, were collected with the use of medical records. Surgically removed tumor tissue specimens were examined by two independent pathologists at the pathology department of our institution. Protein tyrosine kinase-7 expression status was assessed with immunohistochemical processing and stratified on a scale ranging from 0 to +3 according to the extent of stained tumor cells. It was then further categorized into two groups, one being + (positive), including +1, +2, and +3 scores, another was-(negative), including-and +/− scores.Results: A total of 114 patients were analyzed. Protein tyrosine kinase-7 expression was present in 66.7% of the surgical tumor specimens.Therewasnostatisticallysignificantdifferenceinalmost all relevant parameters between the protein tyrosine kinase-7 positive and negative groups. The estimated median survival in the protein tyrosine kinase-7 positive group was significantly better than the protein tyrosine kinase-7 negative group (60 vs 22 months, p

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1. Siegel RL, Miller KD, Jemal A. Cancer Statistics, 2017. CA Cancer J Clin 2017;67:7-30.
2. Youn HG, An JY, Choi MG, Noh JH, Sohn TS, Kim S. Recurrence after curative resection of early gastric cancer. Ann Surg Oncol 2010;17:448-54.
3. Yoo CH, Noh SH, Shin DW, Choi SH, Min JS. Recurrence following curative resection for gastric carcinoma. Br J Surg 2000;87:236-42.
4. Baiocchi GL, Marrelli D, Verlato G, Morgagni P, Giacopuzzi S, Coniglio A, et al. Follow-up after gastrectomy for cancer: an appraisal of the Italian research group for gastric cancer. Ann Surg Oncol 2014;21:2005-11.
5. Macdonald JS, Smalley SR, Benedetti J, Hundahl SA, Estes NC, Stemmermann GN, et al. Chemoradiotherapy after surgery compared with surgery alone for adenocarcinoma of the stomach or gastroesophageal junction. N Engl J Med 2001;345:725-30.
6. Lee J, Lim DH, Kim S, Park SH, Park JO, Park YS, et al. Phase III trial comparing capecitabine plus cisplatin versus capecitabine plus cisplatin with concurrent capecitabine radiotherapy in completely resected gastric cancer with D2 lymph node dissection: the ARTIST trial. J Clin Oncol 2012;30:268-73.
7. Cao L, Selby LV, Hu X, Zhang Y, Janjigian YY, Tang L, et al. Risk factors for recurrence in T1-2N0 gastric cancer in the United States and China. J Surg Oncol 2016;113:745-9.
8. Chau I, Norman AR, Cunningham D, Waters JS, Oates J, Ross PJ. Multivariate prognostic factor analysis in locally advanced and metastatic esophago-gastric cancer--pooled analysis from three multicenter, randomized, controlled trials using individual patient data. J Clin Oncol 2004;22:2395-403.
9. Karpeh MS, Leon L, Klimstra D, Brennan MF. Lymph node staging in gastric cancer: is location more important than Number? An analysis of 1,038 patients. Ann Surg 2000;232:362-71.
10. Mossie K, Jallal B, Alves F, Sures I, Plowman GD, Ullrich A. Colon carcinoma kinase-4 defines a new subclass of the receptor tyrosine kinase family. Oncogene 1995;11:2179-84.
11. Shnitsar I, Borchers A. PTK7 recruits dsh to regulate neural crest migration. Development 2008;135:4015-24.
12. Puppo F, Thomé V, Lhoumeau AC, Cibois M, Gangar A, Lembo F, et al. Protein tyrosine kinase 7 has a conserved role in Wnt/β-catenin canonical signalling. EMBO Rep 2011;12:43-9.
13. Lu X, Borchers AG, Jolicoeur C, Rayburn H, Baker JC, Tessier-Lavigne M. PTK7/CCK-4 is a novel regulator of planar cell polarity in vertebrates. Nature 2004;430:93-8.
14. Van Camp JK, Beckers S, Zegers D, Van Hul W. Wnt signaling and the control of human stem cell fate. Stem Cell Rev 2014;10:207-29.
15. Merrill BJ. Wnt pathway regulation of embryonic stem cell self-renewal. Cold Spring Harb Perspect Biol 2012;4:a007971.
16. Shin WS, Kwon J, Lee HW, Kang MC, Na HW, Lee ST, et al. Oncogenic role of protein tyrosine kinase 7 in esophageal squamous cell carcinoma. Cancer Sci 2013;104:1120-6.
17. Prebet T, Lhoumeau AC, Arnoulet C, Aulas A, Marchetto S, Audebert S, et al. The cell polarity PTK7 receptor acts as a modulator of the chemotherapeutic response in acute myeloid leukemia and impairs clinical outcome. Blood 2010;116:2315-23.
18. Müller-Tidow C, Schwäble J, Steffen B, Tidow N, Brandt B, Becker K, et al. High-throughput analysis of genome-wide receptor tyrosine kinase expression in human cancers identifies potential novel drug targets. Clin Cancer Res 2004;10:1241-9.
19. Gobble RM, Qin LX, Brill ER, Angeles CV, Ugras S, O'Connor RB, et al. Expression profiling of liposarcoma yields a multigene predictor of patient outcome and identifies genes that contribute to liposarcomagenesis. Cancer Res 2011;71:2697-705.
20. Zhang H, Wang A, Qi S, Cheng S, Yao B, Xu Y. Protein tyrosine kinase 7 (PTK7) as a predictor of lymph node metastases anda novel prognosticbiomarker in patients with prostate cancer. Int J Mol Sci 2014;15:11665-77.
21. Lhoumeau AC, Martinez S, Boher JM, Monges G, Castellano R, Goubard A, et al. Overexpression of the Promigratory and Prometastatic PTK7 Receptor Is Associated with an Adverse Clinical Outcome in Colorectal Cancer. PLoS One 2015;10:e0123768.
22. Jin J, Ryu HS, Lee KB, Jang JJ. High expression of protein tyrosine kinase 7 significantly associates with invasiveness and poor prognosis in intrahepatic cholangiocarcinoma. PLoS One 2014;9:e90247.
23. Gärtner S, Gunesch A, Knyazeva T, Wolf P, Högel B, Eiermann W, et al. PTK 7 is a transforming gene and prognostic marker for breast cancer and nodal metastasis involvement. PLoS One.2014;9:e84472.
24. Lin Y, Zhang LH, Wang XH, Xing XF, Cheng XJ, Dong B, et al. PTK7 as a novel marker for favorable gastric cancer patient survival. J Surg Oncol 2012;106:880-6.
25. Dong Y, Chen X, Li H, Ni Y, Han W, Wang J. PTK7 is a molecular marker for metastasis, TNM stage, and prognosis in oral tongue squamous cell carcinoma. Pol J Pathol 2017;68:49-54.
26. Sun JJ, Li HL, Guo SJ, Ma H, Liu SJ, Liu D, et al. The Increased PTK7 Expression Is a Malignant Factor in Cervical Cancer. Dis Markers 2019;2019:5380197.
27. Tian X, Yan L, Zhang D, Guan X, Dong B, Zhao M, et al. PTK7 overexpression in colorectal tumors: Clinicopathological correlation and prognosis relevance. Oncol Rep 2016;36:1829-36.