Expression of CDKL5 in gastric cancer tissue and its clinicopathologic significance_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

 CHEN Jianrong , ZHU Guanghui

Department of General Surgery, Shanghai Fengxian District Central Hospital, Shanghai 201499, P.R.China;

Corresponding?author：

CHEN Jianrong, Email: zhuzhu19820515@126.com

Keywords：

gastric cancer; CDKL5; clinicopathologic characteristics

DOI：

10.7507/1007-9424.201608033

Video：

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Objective To study relation between expression of cyclin-dependent kinase like 5 (CDKL5) in gastric cancer tissue and clinicopathologic characteristics of patients with gastric cancer. Methods The expressions of CDKL5 mRNA and protein in 45 gastric cancer tissues and their corresponding adjacent tissues were detected by real-time quantitative PCR and Western blot methods respectively. Meanwhile the expressions of CDKL5 protein in gastric cancer cell lines including AGS and MKN-45 were detected by immunofluorescence method. Results The CDKL5 mRNA and protein highly expressed in the 45 primary gastric cancer tissues as compared with the their corresponding adjacent tissues (P<0.05). The results of univariate analysis identified that the age (P=0.033), vascular invasion (P=0.007), T stage (P=0.049), and TNM stage (P=0.041) were associated with the expression of CDKL5 mRNA in the primary gastric cancer tissues. The results of multivariate regression analysis showed that the vascular invasion (P=0.013) and TNM stage (P=0.024) were the important factors affecting the expression of CDKL5 in the primary gastric cancer tissues. The CDKL5 protein expressions were found at fragments with relative molecular masses of 107×10³ and 85×10³ in the primary gastric cancer tissues and gastric cancer cell lines. Conclusions CDKL5 mRNA and protein highly express in primary gastric cancer tissue and relate to vascular invasion and TNM stage. The CDKL5 protein expresses at fragments with relative molecular masses of 107×10³ and 85×10³ in primary gastric cancer tissues and gastric cancer cell lines suggest that CDKL5 has different expressing way in protein level.

Citation： CHEN Jianrong, ZHU Guanghui. Expression of CDKL5 in gastric cancer tissue and its clinicopathologic significance. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2017, 24(5): 587-592. doi: 10.7507/1007-9424.201608033 Copy

1.	?Marqués-Lespier JM, González-Pons M, Cruz-Correa M. Current perspectives on gastric cancer. Gastroenterol Clin North Am, 2016, 45(3): 413-428.
2.	Sun W, Yan L. Gastric cancer: current and evolving treatment landscape. Chin J Cancer, 2016, 35(1): 83.
3.	Wan X, Ding X, Chen S, et al. The functional sites of miRNAs and lncRNAs in gastric carcinogenesis. Tumour Biol, 2015, 36(2): 521-532.
4.	da Silva Oliveira KC, Thomaz Araújo TM, Albuquerque CI, et al. Role of miRNAs and their potential to be useful as diagnostic and prognostic biomarkers in gastric cancer. World J Gastroenterol, 2016, 22(35): 7951-7962.
5.	Montini E, Andolfi G, Caruso A, et al. Identification and characterization of a novel serine-threonine kinase gene from the Xp22 region. Genomics, 1998, 51(3): 427-433.
6.	Valli E, Trazzi S, Fuchs C, et al. CDKL5, a novel MYCN-repressed gene, blocks cell cycle and promotes differentiation of neuronal cells. Biochim Biophys Acta, 2012, 1819(11-12): 1173-1185.
7.	García-Pardo MP, Roger-Sanchez C, Rodríguez-Arias M, et al. Pharmacological modulation of protein kinases as a new approach to treat addiction to cocaine and opiates. Eur J Pharmacol, 2016, 781: 10-24.
8.	Sánchez-Martínez C, Gelbert LM, Lallena MJ, et al. Cyclin dependent kinase (CDK) inhibitors as anticancer drugs. Bioorg Med Chem Lett, 2015, 25(17): 3420-3345.
9.	Aleem E, Arceci RJ. Targeting cell cycle regulators in hematologic malignancies. Front Cell Dev Biol, 2015, 3: 16.
10.	Kagami Y, Yoshida K. The functional role for condensin in the regulation of chromosomal organization during the cell cycle. Cell Mol Life Sci, 2016, 73(24): 4591-4598.
11.	Mahipal A, Malafa M. Importins and exportins as therapeutic targets in cancer. Pharmacol Ther, 2016, 164: 135-143.
12.	袁浩, 閔志均, 陳進宏, 等. 甲狀腺乳頭狀癌 TPC-1 細胞中 FoxM1 的表達對 Ras 及 CDK1 的影響. 中國普外基礎與臨床雜志, 2016, 23(2): 172-176.
13.	吳鐸, 徐大方, 趙群, 等. 結直腸癌組織 CDK8 及 TGF-β1 mRNA 和蛋白表達及與其臨床病理因素相關性分析. 中國普外基礎與臨床雜志, 2016, 23(7): 813-817.
14.	Willemsen MH, Rensen JH, van Schrojenstein-Lantman de Valk HM, et al. Adult phenotypes in angelman- and rett-like syndromes. Mol Syndromol, 2012, 2(3-5): 217-234.
15.	Lucariello M, Vidal E, Vidal S, et al. Whole exome sequencing of Rett syndrome-like patients reveals the mutational diversity of the clinical phenotype. Hum Genet, 2016, 135(12): 1343-1354.
16.	Ernst C. Proliferation and differentiation deficits are a major convergence point for neurodevelopmental disorders. Trends Neurosci, 2016, 39(5): 290-299.
17.	Varghese RT, Liang Y, Guan T, et al. Survival kinase genes present prognostic significance in glioblastoma. Oncotarget, 2016, 7(15): 20140-20151.
18.	Vitezic M, Bertin N, Andersson R, et al. CAGE-defined promoter regions of the genes implicated in Rett syndrome. BMC Genomics, 2014, 15: 1177.
19.	Zang ZJ, Ong CK, Cutcutache I, et al. Genetic and structural variation in the gastric cancer kinome revealed through targeted deep sequencing. Cancer Res, 2011, 71(1): 29-39.
20.	Kawahara M, Hori T, Matsubara Y, et al. Cyclin-dependent kinaselike 5 is a novel target of immunotherapy in adult T-cell leukemia. J Immunother, 2007, 30(5): 499-505.
21.	Kawahara M, Hori T, Matsubara Y, et al. Identification of HLA class I-restricted tumor-associated antigens in adult T cell leukemia cells by mass spectrometric analysis. Exp Hematol, 2006, 34(11): 1496-1504.
22.	Lin C, Franco B, Rosner MR. CDKL5/Stk9 kinase inactivation is associated with neuronal developmental disorders. Hum Mol Genet, 2005, 14(24): 3775-3786.
23.	Kameshita I, Sekiguchi M, Hamasaki D, et al. Cyclin-dependent kinase-like 5 binds and phosphorylates DNA methyltransferase 1. Biochem Biophys Res Commun, 2008, 377(4): 1162-1167.
24.	Mari F, Azimonti S, Bertani I, et al. CDKL5 belongs to the same molecular pathway of MeCP2 and it is responsible for the early-onset seizure variant of Rett syndrome. Hum Mol Genet, 2005, 14(14): 1935-1946.
25.	Chen Q, Zhu YC, Yu J, et al. CDKL5, a protein associated with rett syndrome, regulates neuronal morphogenesis via Rac1 signaling. J Neurosci, 2010, 30(38): 12777-12786.
26.	Ricciardi S, Ungaro F, Hambrock M, et al. CDKL5 ensures excitatory synapse stability by reinforcing NGL-1-PSD95 interaction in the postsynaptic compartment and is impaired in patient iPSC-derived neurons. Nat Cell Biol, 2012, 14(9): 911-923.
27.	Zhu YC, Li D, Wang L, et al. Palmitoylation-dependent CDKL5-PSD-95 interaction regulates synaptic targeting of CDKL5 and dendritic spine development. Proc Natl Acad Sci USA, 2013, 110(22): 9118-9123.
28.	Sekiguchi M, Katayama S, Hatano N, et al. Identification of amphiphysin 1 as an endogenous substrate for CDKL5, a protein kinase associated with X-linked neurodevelopmental disorder. Arch Biochem Biophys, 2013, 535(2): 257-267.

1. ?Marqués-Lespier JM, González-Pons M, Cruz-Correa M. Current perspectives on gastric cancer. Gastroenterol Clin North Am, 2016, 45(3): 413-428.
2. Sun W, Yan L. Gastric cancer: current and evolving treatment landscape. Chin J Cancer, 2016, 35(1): 83.
3. Wan X, Ding X, Chen S, et al. The functional sites of miRNAs and lncRNAs in gastric carcinogenesis. Tumour Biol, 2015, 36(2): 521-532.
4. da Silva Oliveira KC, Thomaz Araújo TM, Albuquerque CI, et al. Role of miRNAs and their potential to be useful as diagnostic and prognostic biomarkers in gastric cancer. World J Gastroenterol, 2016, 22(35): 7951-7962.
5. Montini E, Andolfi G, Caruso A, et al. Identification and characterization of a novel serine-threonine kinase gene from the Xp22 region. Genomics, 1998, 51(3): 427-433.
6. Valli E, Trazzi S, Fuchs C, et al. CDKL5, a novel MYCN-repressed gene, blocks cell cycle and promotes differentiation of neuronal cells. Biochim Biophys Acta, 2012, 1819(11-12): 1173-1185.
7. García-Pardo MP, Roger-Sanchez C, Rodríguez-Arias M, et al. Pharmacological modulation of protein kinases as a new approach to treat addiction to cocaine and opiates. Eur J Pharmacol, 2016, 781: 10-24.
8. Sánchez-Martínez C, Gelbert LM, Lallena MJ, et al. Cyclin dependent kinase (CDK) inhibitors as anticancer drugs. Bioorg Med Chem Lett, 2015, 25(17): 3420-3345.
9. Aleem E, Arceci RJ. Targeting cell cycle regulators in hematologic malignancies. Front Cell Dev Biol, 2015, 3: 16.
10. Kagami Y, Yoshida K. The functional role for condensin in the regulation of chromosomal organization during the cell cycle. Cell Mol Life Sci, 2016, 73(24): 4591-4598.
11. Mahipal A, Malafa M. Importins and exportins as therapeutic targets in cancer. Pharmacol Ther, 2016, 164: 135-143.
12. 袁浩, 閔志均, 陳進宏, 等. 甲狀腺乳頭狀癌 TPC-1 細胞中 FoxM1 的表達對 Ras 及 CDK1 的影響. 中國普外基礎與臨床雜志, 2016, 23(2): 172-176.
13. 吳鐸, 徐大方, 趙群, 等. 結直腸癌組織 CDK8 及 TGF-β1 mRNA 和蛋白表達及與其臨床病理因素相關性分析. 中國普外基礎與臨床雜志, 2016, 23(7): 813-817.
14. Willemsen MH, Rensen JH, van Schrojenstein-Lantman de Valk HM, et al. Adult phenotypes in angelman- and rett-like syndromes. Mol Syndromol, 2012, 2(3-5): 217-234.
15. Lucariello M, Vidal E, Vidal S, et al. Whole exome sequencing of Rett syndrome-like patients reveals the mutational diversity of the clinical phenotype. Hum Genet, 2016, 135(12): 1343-1354.
16. Ernst C. Proliferation and differentiation deficits are a major convergence point for neurodevelopmental disorders. Trends Neurosci, 2016, 39(5): 290-299.
17. Varghese RT, Liang Y, Guan T, et al. Survival kinase genes present prognostic significance in glioblastoma. Oncotarget, 2016, 7(15): 20140-20151.
18. Vitezic M, Bertin N, Andersson R, et al. CAGE-defined promoter regions of the genes implicated in Rett syndrome. BMC Genomics, 2014, 15: 1177.
19. Zang ZJ, Ong CK, Cutcutache I, et al. Genetic and structural variation in the gastric cancer kinome revealed through targeted deep sequencing. Cancer Res, 2011, 71(1): 29-39.
20. Kawahara M, Hori T, Matsubara Y, et al. Cyclin-dependent kinaselike 5 is a novel target of immunotherapy in adult T-cell leukemia. J Immunother, 2007, 30(5): 499-505.
21. Kawahara M, Hori T, Matsubara Y, et al. Identification of HLA class I-restricted tumor-associated antigens in adult T cell leukemia cells by mass spectrometric analysis. Exp Hematol, 2006, 34(11): 1496-1504.
22. Lin C, Franco B, Rosner MR. CDKL5/Stk9 kinase inactivation is associated with neuronal developmental disorders. Hum Mol Genet, 2005, 14(24): 3775-3786.
23. Kameshita I, Sekiguchi M, Hamasaki D, et al. Cyclin-dependent kinase-like 5 binds and phosphorylates DNA methyltransferase 1. Biochem Biophys Res Commun, 2008, 377(4): 1162-1167.
24. Mari F, Azimonti S, Bertani I, et al. CDKL5 belongs to the same molecular pathway of MeCP2 and it is responsible for the early-onset seizure variant of Rett syndrome. Hum Mol Genet, 2005, 14(14): 1935-1946.
25. Chen Q, Zhu YC, Yu J, et al. CDKL5, a protein associated with rett syndrome, regulates neuronal morphogenesis via Rac1 signaling. J Neurosci, 2010, 30(38): 12777-12786.
26. Ricciardi S, Ungaro F, Hambrock M, et al. CDKL5 ensures excitatory synapse stability by reinforcing NGL-1-PSD95 interaction in the postsynaptic compartment and is impaired in patient iPSC-derived neurons. Nat Cell Biol, 2012, 14(9): 911-923.
27. Zhu YC, Li D, Wang L, et al. Palmitoylation-dependent CDKL5-PSD-95 interaction regulates synaptic targeting of CDKL5 and dendritic spine development. Proc Natl Acad Sci USA, 2013, 110(22): 9118-9123.
28. Sekiguchi M, Katayama S, Hatano N, et al. Identification of amphiphysin 1 as an endogenous substrate for CDKL5, a protein kinase associated with X-linked neurodevelopmental disorder. Arch Biochem Biophys, 2013, 535(2): 257-267.

CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Expression of CDKL5 in gastric cancer tissue and its clinicopathologic significance

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