Combined detection of the expression of Nm23‑H1 and p53 is correlated with survival rates of patients with stage II and III colorectal cancer

Wu,Yinying; Li,Yi; Zhao,Xiaoai; Dong,Danfeng; Tang,Chunhui; Li,Enxiao; Geng,Qianqian

doi:10.3892/ol.2016.5425

January-2017 Volume 13 Issue 1

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January-2017 Volume 13 Issue 1

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Article Open Access

Combined detection of the expression of Nm23‑H1 and p53 is correlated with survival rates of patients with stage II and III colorectal cancer

Authors:
- Yinying Wu
- Yi Li
- Xiaoai Zhao
- Danfeng Dong
- Chunhui Tang
- Enxiao Li
- Qianqian Geng
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Affiliations: Department of Medical Oncology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China, Department of Geriatrics, Shaanxi Provincial People Hospital, Xi'an, Shaanxi 710068, P.R. China, Department of Nuclear Medicine, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China

Copyright: © Wu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
Pages: 129-136
|
Published online on: November 23, 2016

https://doi.org/10.3892/ol.2016.5425
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Abstract

Molecular tumor markers hold considerable promise for accurately predicting the recurrence and progression of colorectal cancer (CRC) in patients. However, in the majority of cases, single marker analysis has been found to have low accuracy, and is of little practical use in clinical practice. The present study investigated the prognostic value of the combined detection of the protein expression of metastasis suppressor 23‑H1 (Nm23‑H1) and p53 using immunohistochemical analysis, and the mRNA expression levels were analyzed using reverse transcription‑quantitative polymerase chain reaction in 110 cases of stage II and III CRC. The results revealed that the expression levels of Nm23‑H1 in CRC tissues were lower, compared with those in normal tissues (χ2=18.249; P<0.001), and the protein expression levels of p53 were higher in the CRC tissues (χ2=23.940; P<0.001); although the mRNA expression levels of Nm23‑H1 and p53 presented with the same trend. The protein expression of Nm23‑H1 was correlated with lymph node metastases (χ2=11.847; P=0.001) and pathological patterns (χ2=6.911; P=0.032). However, it did not correlate with patient gender or age, or with tumor World Health Organization classification or invasive depth (P>0.05). No significant correlation was observed between the expression of p53 and clinicopathological features (P>0.05). Patients with CRC with Nm23‑H1(+)/p53(‑) tumors had increased survival rates, with a five‑year overall survival rate of 83.8% and a five‑year disease‑free survival rate of 70.2%. The five‑year overall survival rates in other study cohorts were lower, compared with the Nm23‑H1(+)/p53(‑) group (P<0.0125), and this was the same for the five‑year disease‑free survival rate (P<0.0125). In conclusion, the present study demonstrated that the combined detection of the protein expression of Nm23‑H1 and p53 was associated with the long term survival rates of patients with stage II and III CRC; and this may offer potential for use as a predictor of survival rates in patients with CRC.

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1	Siegel R, DeSantis C, Virgo K, Stein K, Mariotto A, Smith T, Cooper D, Gansler T, Lerro C, Fedewa S, et al: Cancer treatment and survivorship statistics, 2012. CA Cancer J Clin. 62:220–241. 2012. View Article : Google Scholar : PubMed/NCBI
2	Nie SF, Yao X, Zhu GB, Zhang JR, Xu YH and Wang X: 1:2 Matched case-control study on risk factors of colorectal cancer in Wuhan. China Public Health. 18:1482–1784. 2002.
3	Li J, Guo BC, Sun LR, Wang JW, Fu XH, Zhang SZ, Poston G and Ding KF: TNM staging of colorectal cancer should be reconsidered by T stage weighting. Worl J Gastroenterol. 20:5104–5112. 2014. View Article : Google Scholar
4	Uen YH, Lin SR, Wu DC, Su YC, Wu JY, Cheng TL, Chi CW and Wang JY: Prognostic significance of multiple molecular markers for patients with stage II colorectal cancer undergoing curative resection. Ann Surg. 246:1040–1046. 2007. View Article : Google Scholar : PubMed/NCBI
5	Voorneveld PW, Jacobs RJ, Kodach LL and Hardwick JC: A meta-analysis of SMAD4 immunohistochemistry as a prognostic marker in colorectal cancer. Transl Oncol. 8:18–24. 2015. View Article : Google Scholar : PubMed/NCBI
6	Kim HO, Kim BG, Cha SJ, Park YG and Lee TJ: Clinicopathologic significance of BRAF mutation and extracellular signal regulated kinase 1/2 expression in patients with a colorectal adenocarcinoma. Ann Coloproctol. 31:9–15. 2015. View Article : Google Scholar : PubMed/NCBI
7	Wu HW, Gao LD and Wei GH: hMSH2 and nm23 expression in sporadic colorectal cancer and its clinical significance. Asian Pac J Cancer Prev. 14:1995–1998. 2013. View Article : Google Scholar : PubMed/NCBI
8	Suzuki E, Ota T, Tsukuda K, Okita A, Matsuoka K, Murakami M, Doihara H and Shimizu N: Nm23-H1 reduces in vitro cell migration and the liver metastatic potential of colon cancer cells by regulating myosin light chain phosphorylation. Int J Cancer. 108:207–211. 2004. View Article : Google Scholar : PubMed/NCBI
9	Bal A, Joshi K, Logasundaram R, Radotra BD and Singh R: Expression of nm23 in the spectrum of pre-invasive, invasive and metastatic breast lesions. Diagn Pathol. 3:232008. View Article : Google Scholar : PubMed/NCBI
10	Nakayama T, Ohtsuru A, Nakao K, Shima M, Nakata K, Watanabe K, Ishii N, Kimura N and Nagataki S: Expression in human hepatocellular carcinoma of nucleoside diphosphate kinase, a homologue of the nm23 gene product. J Natl Cancer Inst. 84:1349–1354. 1992. View Article : Google Scholar : PubMed/NCBI
11	Zhao Z, Lu P, Zhang H, Xu H, Gao N, Li M and Liu C: Nestin positively regulates the Wnt/ß-catenin pathway and the proliferation, survival and invasiveness of breast cancer stem cells. Breast Cancer Res. 16:4082014. View Article : Google Scholar : PubMed/NCBI
12	Mandai M, Konishi I, Koshiyama M, Mori T, Arao S, Tashiro H, Okamura H, Normura H, Hiai H and Fukumoto M: Expression of metastasis-related nm23-H1 and nm23-H2 genes in ovarian carcinomas: Correlation with clinicopathology, EGFR, c-erbB-2, and c-erbB-3 genes, and sex steroid receptor expression. Cancer Res. 54:1825–1830. 1994.PubMed/NCBI
13	Cheok CF, Verma CS, Baselqa J and Lane DP: Translating p53 into clinic. Nat Rev Clin Oncol. 8:25–37. 2011. View Article : Google Scholar : PubMed/NCBI
14	Vogelstein B, Lane DP and Levine AJ: Suring the p53 network. Nature. 408:307–310. 2000. View Article : Google Scholar : PubMed/NCBI
15	Liu W, Yu YH, Ouyang XN, Wang L, Wu YM, Chen J and Xiong XS: Clinical significance of p53 and Ki67 expression in gastric cancer. World J. Gastroenterol. 19:367–373. 2011.
16	Ma LL, Zhe W, Wang YQ, Cong XL and Zhang XM: Expression and clinical significance of Survivin and p53 in breast cancer. Chin J Exp Surg. 31:2839–2840. 2014.
17	Zhang YX and Wang Y: Clinical significance and expression of p53 in colorectal cancer. World J Integrated Traditional and Western Med. 2:294–296. 2007.
18	Xiao ZW, He N, Cao JQ, Li ZJB and Zhu ZM: The relationship between the expression of MMP-2 and p53 and tumor invasion and metastasis in colorectal carcinoma. The Practical J Cancer. 24:39–43. 2009.
19	Yin H, Xu L and Yao HW: New opinions of colorectal cancer in 2010. Chin J Practical Surg. 30:764–768. 2010.
20	Hyslop T, Weinberg DS, Schulz S, Barkun A and Waldman SA: Analytic lymph node number establishes staging accuracy by occult tumor burden in colorectal cancer. J Surg Oncol. 106:24–30. 2012. View Article : Google Scholar : PubMed/NCBI
21	Gao P, Song YX, Wang ZN, Xu YY, Tong LL, Sun JX, Yu M and Xu HM: Is the prediction of prognosis not improved by the seventh edition of TNM classification for colorectal cancer? Analysis of the surveillance, epidemiology, and end results (SEER) database. BMC Cancer. 13:1232013. View Article : Google Scholar : PubMed/NCBI
22	Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(−Delta Delta C(T)) Method. Methods. 25:402–408. 2001. View Article : Google Scholar : PubMed/NCBI
23	Backer JM, Mendola CE, Kovesdi I, Fairhurst JL, O'Hara B, Eddy RL Jr, Shows TB, Mathew S, Murty VV and Chaganti RS: Chromosomal localization and nucleoside diphosphate kinase activity of human metastasis suppressor genes nm23-1 and nm23-2. Oncogene. 8:497–502. 1993.PubMed/NCBI
24	Kim HD, Youn B, Kim TS, Kim SH, Shin HS and Kim J: Regulators affecting the metastasis suppressor activity of Nm23-H1. Mol Cell Biochem. 329:167–173. 2009. View Article : Google Scholar : PubMed/NCBI
25	Lombardi D, Lacombe ML and Paggi MG: Nm23: Unraveling its biological function in cell differentiation. J Cell Physiol. 182:144–149. 2000. View Article : Google Scholar : PubMed/NCBI
26	Yang YQ and Li JC: Correlation of genetic instablity of nm23H1 and clinicopathologic features of epithelial in ovarian carcinoma. Ai Zheng. 25:713–717. 2006.(In Chinese). PubMed/NCBI
27	Zheng HX, Cui YX, Shen DL, Peng A and He YL: Influence of nm23-H1 gene transfection on expression of MMP-9 and TIMP-1 in lung cancer cells. Chin Clin Oncol. 20:104–107. 2015.
28	Dusonchet L, Corsale S, Migliavacca M, Calò V, Bazan V, Amato A, Cammareri P, Totaro MS, Agnese V, Cascio S, et al: Nm23-H1 expression does not predict clinical survival in colorectal cancer patients. Oncol Rep. 10:1257–1263. 2003.PubMed/NCBI
29	Song JM, Kelton G and Wang JJ: Review colorectal cancer screening: Current available methods. Chin General Practice. 11:1115–1120. 2008.
30	Zhao R, Gong L, Li L, Guo L, Zhu D, Wu Z and Zhou Q: Nm23-H1 is a negative regulator of TGF-β1-dependent induction of epithelial-mesenchymal transition. Exp Cell Res. 319:740–749. 2013. View Article : Google Scholar : PubMed/NCBI
31	Selivanova G: Wild type p53 reaction: From lab bench to clinic. FEBS Lett. 588:2628–2638. 2014. View Article : Google Scholar : PubMed/NCBI
32	Chang YS, Graves B, Guerlavais V, Tovar C, Packman K, To KH, Olson KA, Kesavan K, Gangurde P, Muknherjee A, et al: Stapled α-helical peptide drug development: A potent dual inhibitor of MDM2 and MDMX for p53-dependent canceer therapy. Proc Natl Acad Sci USA. 110:E3445–E3454. 2013. View Article : Google Scholar : PubMed/NCBI
33	Zhou XF, Zhang G and Tian Y: P53 status correlates with the risk of recurrence in non-muscle invasive bladder cancers treated with bacillus calmette Guérin: A meta-analysis. PLoS One. 10:e01194762015. View Article : Google Scholar : PubMed/NCBI
34	Dolicanin Z, Velicković LJ, Djordjević B, Visnjić M, Pesić I, Ristić A and Marianović V: Expression of regulatory proteins and proliferative activity in relation to phenotypic characteristics of upper urothelial carcinoma. Vojnosanit Pregl. 68:567–574. 2011. View Article : Google Scholar : PubMed/NCBI
35	da Silva GN, Evangelista AF, Magalhães DA, Macedo C, Búfalo MC, Sakamoto-Hojo ET, Passos GA and Saladori DM: Expression of genes related to apoptosis, cell cycle and signaling pathways are independent of TP53 status in urinary bladder cancer cells. Mol Biol Rep. 38:4159–4170. 2011. View Article : Google Scholar : PubMed/NCBI
36	Chen XY, Shi ZL and Li YH: Co-expression of P-gp, GST, TOP II and p53 in colorectal carcinoma. J Clin Exp Pathol. 18:608–610. 2002.
37	Lu Y, Gao J and Lu Y: Down-expression pattern of Ku70 and p53 coexisted in colorectal cancer. Med Oncol. 32:982015. View Article : Google Scholar : PubMed/NCBI
38	Ye B, Wang XC, Lei L and You LS: Expression and clinical significances of p53 and Ki67 in colorectal carcinoma. The Practical J Cancer. 28:42–44. 2013.
39	Liu BW, Liu Y, Liu JR, Feng ZX and Liu T: Prognositic effect of p53 expression in patients with completely resected colorectal cancer. Tumour Biol. 35:9893–9896. 2014. View Article : Google Scholar : PubMed/NCBI
40	Geng QQ, Li Y, Tang CH, Li EX, Wu YY and Zhang GJ: Expression and clinical significance of vascular endothelial growth factor-C and nm23-H1 in stage II and III colorectal carcinomas. Zhonghua Zhong Liu Za Zhi. 35:439–444. 2013.(In Chinese). PubMed/NCBI
41	Radović S, Dorić M, Hukić A, Babić M, Kuskunović S and Spahović N: Immunohistochemical expression and significance of Nm23 suppressor protein in primary gastric adenocarcinoma. Bosn J Basic Med Sci. 13:72–77. 2013.PubMed/NCBI
42	Porebska I, Kosacka M, Wyrodek E and Jankowska R: Expression of p53, bcl-2 and nm23 protein in squamous cell lung cancer. Pneumonol Alergol Pol. 77:131–137. 2009.(In Polish). PubMed/NCBI