nach oben

Medical Oncology

Erschienen in:

01.12.2014 | Original Paper

Downregulated expression of PTK6 is correlated with poor survival in esophageal squamous cell carcinoma

verfasst von: You-Fang Chen, Gang Ma, Xun Cao, Zhi-Liang Huang, Mu-Sheng Zeng, Zhe-Sheng Wen

Erschienen in: Medical Oncology | Ausgabe 12/2014

Einloggen, um Zugang zu erhalten

Abstract

To investigate the clinical prognostic value of protein tyrosine kinase 6 (PTK6) in patients with esophageal squamous cell carcinoma (ESCC), quantitative RT-PCR and Western blotting were utilized to measure the mRNA and protein expression levels of PTK6 in 29 and eight pairs of ESCC and peritumoral normal esophageal tissues, respectively. Furthermore, the expression of PTK6 protein in 210 ESCCs was examined with immunohistochemistry (IHC), and its clinical value was analyzed using Kaplan–Meier plots and the Cox proportional hazards regression model. The results found that the expression levels of both PTK6 mRNA and protein in ESCC tissues were significantly lower than those in peritumoral normal esophageal tissues. Regarding the IHC analysis of ESCC, the cytoplasmic expression of PTK6 was significantly correlated with tumor grade (P < 0.001). Compared with patients with low PTK6 expression, ESCC patients with overexpression of PTK6 displayed preferable disease-free survival (DFS) and overall survival (OS) (P < 0.001 and P = 0.001, respectively), especially in stage II disease (P = 0.002 and P = 0.021, respectively). PTK6 was evaluated as an independent prognostic factor for ESCC using multivariate Cox regression analysis. All data demonstrated that the expression level of PTK6 is an independent prognostic factor in ESCCs. Low expression of PTK6 is correlated with poor DFS and OS in ESCCs.

Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA Cancer J Clin. 2011;61(2):69–90.PubMedCrossRef

Guo P, Li K. Trends in esophageal cancer mortality in China during 1987–2009: age, period and birth cohort analyzes. Cancer Epidemiol. 2012;36(2):99–105.PubMedCrossRef

Tran GD, Sun XD, Abnet CC, Fan JH, Dawsey SM, Dong ZW, et al. Prospective study of risk factors for esophageal and gastric cancers in the Linxian general population trial cohort in China. Int J Cancer. 2005;113(3):456–63.PubMedCrossRef

Enzinger PC, Mayer RJ. Esophageal cancer. New Engl J Med. 2003;349(23):2241–52.PubMedCrossRef

Siyanova EY, Serfas MS, Mazo IA, Tyner AL. Tyrosine kinase gene expression in the mouse small intestine. Oncogene. 1994;9(7):2053–7.PubMed

Vasioukhin V, Tyner AL. A role for the epithelial-cell-specific tyrosine kinase Sik during keratinocyte differentiation. Proc Natl Acad Sci USA. 1997;94(26):14477–82.PubMedCentralPubMedCrossRef

Derry JJ, Prins GS, Ray V, Tyner AL. Altered localization and activity of the intracellular tyrosine kinase BRK/Sik in prostate tumor cells. Oncogene. 2003;22(27):4212–20.PubMedCrossRef

Petro BJ, Tan RC, Tyner AL, Lingen MW, Watanabe K. Differential expression of the non-receptor tyrosine kinase BRK in oral squamous cell carcinoma and normal oral epithelium. Oral Oncol. 2004;40(10):1040–7.PubMedCrossRef

Kasprzycka M, Majewski M, Wang ZJ, Ptasznik A, Wysocka M, Zhang Q, et al. Expression and oncogenic role of Brk (PTK6/Sik) protein tyrosine kinase in lymphocytes. Am J Pathol. 2006;168(5):1631–41.PubMedCentralPubMedCrossRef

10.

Llor X, Serfas MS, Bie W, Vasioukhin V, Polonskaia M, Derry J, et al. BRK/Sik expression in the gastrointestinal tract and in colon tumors. Clin Cancer Res. 1999;5(7):1767–77.PubMed

11.

Vasioukhin V, Serfas MS, Siyanova EY, Polonskaia M, Costigan VJ, Liu B, et al. A novel intracellular epithelial cell tyrosine kinase is expressed in the skin and gastrointestinal tract. Oncogene. 1995;10(2):349–57.PubMed

12.

Locatelli A, Lofgren KA, Daniel AR, Castro NE, Lange CA. Mechanisms of HGF/Met signaling to Brk and Sam68 in breast cancer progression. Horm Cancer. 2012;3(1–2):14–25.PubMedCentralPubMedCrossRef

13.

Schmandt RE, Bennett M, Clifford S, Thornton A, Jiang F, Broaddus RR, et al. The BRK tyrosine kinase is expressed in high-grade serous carcinoma of the ovary. Cancer Biol Ther. 2006;5(9):1136–41.PubMedCrossRef

14.

Haegebarth A, Nunez R, Tyner AL. The intracellular tyrosine kinase Brk sensitizes non-transformed cells to inducers of apoptosis. Cell Cycle. 2005;4(9):1239–46.PubMedCrossRef

15.

Ludyga N, Anastasov N, Gonzalez-Vasconcellos I, Ram M, Hofler H, Aubele M. Impact of protein tyrosine kinase 6 (PTK6) on human epidermal growth factor receptor (HER) signalling in breast cancer. Mol BioSyst. 2011;7(5):1603–12.PubMedCrossRef

16.

Liu XK, Zhang XR, Zhong Q, Li MZ, Liu ZM, Lin ZR, et al. Low expression of PTK6/Brk predicts poor prognosis in patients with laryngeal squamous cell carcinoma. J Transl Med. 2013;11:59.PubMedCentralPubMedCrossRef

17.

Zhao C, Chen Y, Zhang W, Zhang J, Xu Y, Li W, et al. Expression of protein tyrosine kinase 6 (PTK6) in nonsmall cell lung cancer and their clinical and prognostic significance. Onco Targets Ther. 2013;6:183–8.PubMedCentralPubMed

18.

Liu LN, Huang PY, Lin ZR, Hu LJ, Liang JZ, Li MZ, et al. Protein tyrosine kinase 6 is associated with nasopharyngeal carcinoma poor prognosis and metastasis. J Transl Med. 2013;11:140.PubMedCentralPubMedCrossRef

19.

Easty DJ, Mitchell PJ, Patel K, Florenes VA, Spritz RA, Bennett DC. Loss of expression of receptor tyrosine kinase family genes PTK7 and SEK in metastatic melanoma. Int J Cancer. 1997;71(6):1061–5.PubMedCrossRef

20.

Haegebarth A, Perekatt AO, Bie W, Gierut JJ, Tyner AL. Induction of protein tyrosine kinase 6 in mouse intestinal crypt epithelial cells promotes DNA damage-induced apoptosis. Gastroenterology. 2009;137(3):945–54.PubMedCentralPubMedCrossRef

21.

Haegebarth A, Bie W, Yang R, Crawford SE, Vasioukhin V, Fuchs E, et al. Protein tyrosine kinase 6 negatively regulates growth and promotes enterocyte differentiation in the small intestine. Mol Cell Biol. 2006;26(13):4949–57.PubMedCentralPubMedCrossRef

22.

Lofgren KA, Ostrander JH, Housa D, Hubbard GK, Locatelli A, Bliss RL, et al. Mammary gland specific expression of Brk/PTK6 promotes delayed involution and tumor formation associated with activation of p38 MAPK. Breast Cancer Res. 2011;13(5):R89.PubMedCentralPubMedCrossRef

23.

Li X, Lu Y, Liang K, Hsu JM, Albarracin C, Mills GB, et al. Brk/PTK6 sustains activated EGFR signaling through inhibiting EGFR degradation and transactivating EGFR. Oncogene. 2012;31(40):4372–83.PubMedCentralPubMedCrossRef

24.

Aubele M, Auer G, Walch AK, Munro A, Atkinson MJ, Braselmann H, et al. PTK (protein tyrosine kinase)-6 and HER2 and 4, but not HER1 and 3 predict long-term survival in breast carcinomas. Br J Cancer. 2007;96(5):801–7.PubMedCentralPubMedCrossRef

25.

Aubele M, Walch AK, Ludyga N, Braselmann H, Atkinson MJ, Luber B, et al. Prognostic value of protein tyrosine kinase 6 (PTK6) for long-term survival of breast cancer patients. Br J Cancer. 2008;99(7):1089–95.PubMedCentralPubMedCrossRef

26.

Luo H, Yang Y, Huang F, Li F, Jiang Q, Shi K, et al. Selenite induces apoptosis in colorectal cancer cells via AKT-mediated inhibition of beta-catenin survival axis. Cancer Lett. 2012;315(1):78–85.PubMedCrossRef

27.

Zhang P, Ostrander JH, Faivre EJ, Olsen A, Fitzsimmons D, Lange CA. Regulated association of protein kinase B/Akt with breast tumor kinase. J Biol Chem. 2005;280(3):1982–91.PubMedCrossRef

28.

Ma S, Bao JY, Kwan PS, Chan YP, Tong CM, Fu L, et al. Identification of PTK6, via RNA sequencing analysis, as a suppressor of esophageal squamous cell carcinoma. Gastroenterology. 2012;143(3):675–86 e1–12.

29.

Cao X, Li Y, Luo RZ, He LR, Yang J, Zeng MS, et al. Tyrosine-protein phosphatase nonreceptor type 12 is a novel prognostic biomarker for esophageal squamous cell carcinoma. Ann Thora Surg. 2012;93(5):1674–80.CrossRef

30.

Fermento ME, Gandini NA, Lang CA, Perez JE, Maturi HV, Curino AC, et al. Intracellular distribution of p300 and its differential recruitment to aggresomes in breast cancer. Exp Mol Pathol. 2010;88(2):256–64.PubMedCrossRef

31.

Jiang S, Li Y, Zhu YH, Wu XQ, Tang J, Li Z, et al. Intensive expression of UNC-51-like kinase 1 is a novel biomarker of poor prognosis in patients with esophageal squamous cell carcinoma. Cancer Sci. 2011;102(8):1568–75.PubMedCrossRef

32.

Olaussen KA, Dunant A, Fouret P, Brambilla E, Andre F, Haddad V, et al. DNA repair by ERCC1 in non-small-cell lung cancer and cisplatin-based adjuvant chemotherapy. New Engl J Med. 2006;355(10):983–91.PubMedCrossRef

33.

Ostrander JH, Daniel AR, Lange CA. Brk/PTK6 signaling in normal and cancer cell models. Curr Opin Pharmacol. 2010;10(6):662–9.PubMedCentralPubMedCrossRef

34.

Brauer PM, Zheng Y, Wang L, Tyner AL. Cytoplasmic retention of protein tyrosine kinase 6 promotes growth of prostate tumor cells. Cell Cycle. 2010;9(20):4190–9.PubMedCentralPubMedCrossRef

35.

Gaur P, Hofstetter WL, Bekele BN, Correa AM, Mehran RJ, Rice DC, et al. Comparison between established and the Worldwide Esophageal Cancer Collaboration staging systems. Ann Thorac Surg. 2010;89(6):1797–803, 1804 e1–3; discussion 1803–4.

Titel: Downregulated expression of PTK6 is correlated with poor survival in esophageal squamous cell carcinoma
verfasst von: You-Fang Chen
Gang Ma
Xun Cao
Zhi-Liang Huang
Mu-Sheng Zeng
Zhe-Sheng Wen
Publikationsdatum: 01.12.2014
Verlag: Springer US
Erschienen in: Medical Oncology / Ausgabe 12/2014
Print ISSN: 1357-0560
Elektronische ISSN: 1559-131X
DOI: https://doi.org/10.1007/s12032-014-0317-9

Neu im Fachgebiet Onkologie

23.04.2024 | Medikamente in Schwangerschaft und Stillzeit | Nachrichten

Live-Webinar: Aktuelle Leitlinien bei Herz-Kreislauf-Erkrankungen

Springer Medizin

Downregulated expression of PTK6 is correlated with poor survival in esophageal squamous cell carcinoma

Abstract

Neu im Fachgebiet Onkologie

ICI-Therapie in der Schwangerschaft wird gut toleriert

Krebspatienten impfen: Was? Wen? Und wann nicht?

Müde im Alter? Auch an die Nebenniere denken

Stufenschema weist Prostatakarzinom zuverlässig nach

Update Onkologie

Live-Webinar: Aktuelle Leitlinien bei Herz-Kreislauf-Erkrankungen

Springer Medizin

Abstract

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten

Weitere Artikel der Ausgabe 12/2014

Functional polymorphisms of circadian negative feedback regulation genes are associated with clinical outcome in hepatocellular carcinoma patients receiving radical resection

Stereotactic body radiotherapy with concurrent chemotherapy extends survival of patients with limited stage small cell lung cancer: a single-center prospective phase II study

The expression of Toll-like receptors and development of severe sepsis in patients with acute myeloid leukemias after induction chemotherapy

OSNA (one-step nucleic acid amplification) sentinel lymph node intraoperative molecular analysis in breast cancer: a cost-benefit analysis

A prognostic model based on pretreatment platelet lymphocyte ratio for stage IE/IIE upper aerodigestive tract extranodal NK/T cell lymphoma, nasal type

Re-challenge with catumaxomab in patients with malignant ascites: results from the SECIMAS study

Neu im Fachgebiet Onkologie

ICI-Therapie in der Schwangerschaft wird gut toleriert

Krebspatienten impfen: Was? Wen? Und wann nicht?

Müde im Alter? Auch an die Nebenniere denken

Stufenschema weist Prostatakarzinom zuverlässig nach

Update Onkologie