The role of NM23 in patients with colorectal cancer: A systematic review and meta-analysis

Abstract

This meta-analysis was carried out to evaluate the relationship between NM23 expression and the prognosis of patients with colorectal cancer. We searched PubMed, EMBASE and Web of Science for relevant articles. The pooled odd ratios (ORs) and corresponding 95%CI were calculated to evaluate the prognostic value of NM23 expression in patients with colorectal cancer, and the association between NM23 expression and clinicopathological factors. In total, 2289 patients were pooled from 24 available studies. The incorporative OR combined by 16 studies with overall survival showed that high NM23 expression was associated with better overall survival (OR=0.67, 95%CI: 0.49–0.93, P=0.02, I²=56%, Ph=0.004). And a new estimate without heterogeneity was produced when only combining high-quality studies (OR=0.70, 95%CI: 0.56–0.86, P=0.0007, I²=46%). In disease free survival (DFS), we also obtained a good prognosis (OR=0.30, 95%CI: 0.14–0.68, P=0.004). Although we failed to find any significance in N status (P=0.10), elevated NM23 expression was related to well tumor differentiation (OR=0.60, 95%CI: 0.44–0.820, P=0.001) and Dukes’ A&B (OR=0.55, 95%CI: 0.32–0.95, P=0.03). These results indicated that over-expressed NM23 might be an indicator of good prognosis, well tumor differentiation and Dukes’ A&B of patients with colorectal cancer, but no significance was found in N status.

Keywords

NM23 / colorectal cancer / prognosis / survival and meta-analysis

References

[1] SiegelRL, MillerKD, JemalA. Cancer statistics, 2015. CA Cancer J Clin, 2015, 65(1): 5-29 PMID: 25559415

[2] NgL, PoonRT, PangR. Biomarkers for predicting future metastasis of human gastrointestinal tumors. Cell Mol Life Sci, 2013, 70(19): 3631-3656 PMID: 23370778

[3] HariDM, LeungAM, LeeJH, et al. . AJCC Cancer Staging Manual 7th edition criteria for colon cancer: do the complex modifications improve prognostic assessment?. J Am Coll Surg, 2013, 217(2): 181-190 PMID: 23768788 PMCID: 4657944

[4] JensenSL, WoodDP, BanksER, et al. . Increased levels of nm23 H1/nucleoside diphosphate kinase A mRNA associated with adenocarcinoma of the prostate. World J Urol, 1996, 14: S21-25 PMID: 8738406

[5] KhanMH, YasudaM, HigashinoF, et al. . nm23-H1 suppresses invasion of oral squamous cell carcinoma-derived cell lines without modifying matrix metalloproteinase-2 and matrix metalloproteinase-9 expression. Am J Pathol, 2001, 158(5): 1785-1791 PMID: 11337376 PMCID: 1891946

[6] GaoQL, MaD, MengL, et al. . Association between Nm23-H1 gene expression and metastasis of ovarian carcinoma. Ai Zheng (Chinese), 2004, 23(6): 650-654

[7] LeoneA, FlatowU, KingCR, et al. . Reduced tumor incidence, metastatic potential, and cytokine responsiveness of nm23-transfected melanoma cells. Cell, 1991, 65(1): 25-35 PMID: 2013093

[8] BoissanM, de WeverO, LizarragaF, et al. . Implication of metastasis suppressor NM23-H1 in maintaining adherens junctions and limiting the invasive potential of human cancer cells. Cancer Res, 2010, 70(19): 7710-7722 PMID: 20841469

[9] KushlinskiiNE, YurchenkoAA, DelektorskayaVV, et al. . Relationship between expression of NM23 protein and clinical morphological factors and content of plasminogen activation system components in tumors of patients with gastric cancer. Bull Exp Biol Med, 2007, 143(6): 733-736 PMID: 18239814

[10] KimHJ, KangHJ, LeeH, et al. . Identification of S100A8 and S100A9 as serological markers for colorectal cancer. J Proteome Res, 2009, 8(3): 1368-1379 PMID: 19186948

[11] ElagozS, EgilmezR, KoyuncuA, et al. . The intratumoral microvessel density and expression of bFGF and nm23-H1 in colorectal cancer. Pathol Oncol Res, 2006, 12(1): 21-27 PMID: 16554912

[12] YounBS, KimDS, KimJW, et al. . NM23 as a prognostic biomarker in ovarian serous carcinoma. Modern Pathology, 2008, 21(7): 885-892 PMID: 18408655

[13] YangT, ChenBZ, LiDF, et al. . Reduced NM23 protein level correlates with worse clinicopathologic features in colorectal cancers: a meta-analysis of pooled data. Medicine (Baltimore), 2016, 95(4): pe2589

[14] Han W, Ma J, Cao F, et al. Prognostic value of NM23 in patients with colorectal carcinoma: a systematic review and meta-analysis. PROSPERO, CRD42015029488.

[15] StangA. Critical evaluation of the Newcastle-Ottawa scale for the assessment of the quality of nonrandomized studies in meta-analyses. Eur J Epidemiol, 2010, 25(9): 603-605 PMID: 20652370

[16] WongWC, CheungCS, HartGJ. Development of a quality assessment tool for systematic reviews of observational studies (QATSO) of HIV prevalence in men having sex with men and associated risk behaviours. Emerg Themes Epidemiol, 2008, 5: 23 PMID: 19014686 PMCID: 2603000

[17] EggerM, Davey SmithG, SchneiderM, et al. . Bias in meta-analysis detected by a simple, graphical test. BMJ, 1997, 315(7109): 629-634 PMID: 9310563 PMCID: 2127453

[18] GarinisGA, ManolisEN, SpanakisNE, et al. . High frequency of concomitant nm23-H1 and E-cadherin transcriptional inactivation in primary non-inheriting colorectal carcinomas. J Mol Med, 2003, 81(4): 256-263 PMID: 12684753

[19] MyeroffLL, MarkowitzSD. Increased nm23-H1 and nm23-H2 messenger RNA expression and absence of mutations in colon carcinomas of low and high metastatic potential. J Natl Cancer Inst, 1993, 85(2): 147-152 PMID: 8418304

[20] NobiliS, NapoliC, LandiniI, et al. . Identification of potential pharmacogenomic markers of clinical efficacy of 5-fluorouracil in colorectal cancer. Int J Cancer, 2011, 128(8): 1935-1945 PMID: 20560137

[21] CohnKH, OrnsteinDL, WangFS, et al. . The significance of allelic deletions and aneuploidy in colorectal carcinoma–Results of a 5-year follow-up study. Cancer, 1997, 79(2): 233-244 PMID: 9010096

[22] CaligoMA, GhimentiC, SensiE, et al. . Microsatellite alterations and K-ras, TGF beta RII, IGFRII and bax mutations in sporadic cancers of the gastrointestinal tract. Oncol Rep, 2000, 7(6): 1371-1375 PMID: 11032947

[23] CohnKH, WangF, DeSoto-LaPaixF, et al. . Association of nm23-H1 allelic deletions with distant metastases in colorectal carcinoma. Lancet, 1991, 338(8769): 722-724 PMID: 1679868

[24] LambRF, GoingJJ, PickfordI, et al. . Allelic imbalance at NME1 in microdissected primary and metastatic human colorectal carcinomas is frequent but not associated with metastasis to lymph nodes or liver. Cancer Res, 1996, 56(4): 916-920 PMID: 8631033

[25] LeggettB, YoungJ, ButtenshawR, et al. . Colorectal carcinomas show frequent allelic loss on the long arm of chromosome 17 with evidence for a specific target region. Br J Cancer, 1995, 71(5): 1070-1073 PMID: 7734302 PMCID: 2033787

[26] BerneyCR, FisherRJ, YangJI, et al. . Protein markers in colorectal cancer–Predictors of liver metastasis. Ann Surg, 1999, 230(2): 179-184 PMID: 10450731 PMCID: 1420859

[27] AbadA, OjangurenI, FontA, et al. . Prognostic significance of the nm23-H1 protein expression in colorectal cancer. Eur J Cancer, 1996, 32A: S26-S26

[28] AyhanA, YasuiW, YokozakiH, et al. . Reduced expression of nm23 protein is associated with advanced tumor stage and distant metastases inhuman colorectal carcinomas. Virchows Arch B Cell Pathol Incl Mol Pathol, 1993, 63(4): 213-218 PMID: 8099459

[29] BerneyCR, YangJL, FisherRJ, et al. . Overexpression of nm23 protein assessed by color video image analysis in metastatic colorectal cancer: correlation with reduced patient survival. World J Surg, 1998, 22(5): 484-490 PMID: 9564293

[30] BertucciF, SalasS, EysteriesS, et al. . Gene expression profiling of colon cancer by DNA microarrays and correlation with histoclinical parameters. Oncogene, 2004, 23(7): 1377-1391 PMID: 14973550

[31] CheahPY, CaoX, EuKW, et al. . NM23-H1 immunostaining is inversely associated with tumour staging but not overall survival or disease recurrence in colorectal carcinomas. Br J Cancer, 1998, 77(7): 1164-1168 PMID: 9569056 PMCID: 2150137

[32] ChenWC, LinMS, ZhangBF, et al. . Survey of molecular profiling during human colon cancer development and progression by immunohistochemical staining on tissue microarray. World J Gastroenterol, 2007, 13(5): 699-708 PMID: 17278192 PMCID: 4066002

[33] DursunA, AkyurekN, GunelN, et al. . Prognostic implication of nm23-H1 expression in colorectal carcinomas. Pathology, 2002, 34(5): 427-432 PMID: 12408341

[34] HeysSD, LangloisN, SmithIC, et al. . NM23 gene product expression does not predict lymph node metastases or survival in young patients with colorectal cancer. Oncol Rep, 1998, 5(3): 735-739 PMID: 9538187

[35] IchikawaW. Positive relationship between expression of CD44 and hepatic metastases in colorectal cancer. Pathobiology, 1994, 62(4): 172-179 PMID: 7537507

[36] KapitanovicS, CacevT, BerkovicM, et al. . Nm23-H1 expression and loss of heterozygosity in colon adenocarcinoma. J Clin Pathol, 2004, 57(12): 1312-1318 PMID: 15563674 PMCID: 1770523

[37] LeeJC, LinYJ, ChowNH, et al. . Reappraisal of the role of NM23-H1 in colorectal cancers. J Surg Oncol, 2001, 76(1): 58-62 PMID: 11223826

[38] LindmarkG. NM-23 H1 immunohistochemistry is not useful as predictor of metastatic potential of colorectal cancer. Br J Cancer, 1996, 74(9): 1413-1418 PMID: 8912537 PMCID: 2074791

[39] MadboulyKM, SenagoreAJ, MukerjeeA, et al. . Does immunostaining effectively upstage colorectal cancer by identifying micrometastatic nodal disease?. Int J Colorectal Dis, 2007, 22(1): 39-48 PMID: 16528541

[40] MartinezJ, PrevotS, NordingerB, et al. . Overexpression of nm23-H1 and nm23-H2 genes in colorectal carcinomas and loss of nm23-H1 expression in advanced tumour stages. Gut, 1995, 37(5): 712-720 PMID: 8549951 PMCID: 1382880

[41] MessinettiS, GiacomelliL, FabrizioG, et al. . CD44v6 and Nm23-H1 protein expression related to clinico pathological parameters in colorectal cancer. Ann Ital Chir, 2003, 74(1): 45-51 PMID: 12870281

[42] OliveiraLA, Artigiani-NetoR, WaisbergDR, et al. . NM23 protein expression in colorectal carcinoma using TMA (tissue microarray): association with metastases and survival. Arq Gastroenterol, 2010, 47(4): 361-367 PMID: 21225146

[43] Pasz-WalczakG, SalagackaA, PotemskiP, et al. . Maspin and Nm23-H1 expression in colorectal cancer. Neoplasma, 2010, 57(2): 95-101 PMID: 20099971

[44] SuZH, LiJC. Lymphatic metastasis and nm23H1 genetic instability in Chinese colon cancer patients. World J Gastroenterol, 2004, 10(19): 2800-2804 PMID: 15334673 PMCID: 4572105

[45] TabuchiY, NakamuraT, KuniyasuT, et al. . Expression of nm23-H1 in colorectal cancer: no association with metastases, histological stage, or survival. Surg Today, 1999, 29(2): 116-120 PMID: 10030735

[46] TannapfelA, KockerlingF, KatalinicA, et al. . Expression of nm23-H1 predicts lymph node involvement in colorectal carcinoma. Dis Colon Rectum, 1995, 38(6): 651-654 PMID: 7774480

[47] TripkovicA, TripkovicI, TomicS, et al. . The role of nm23 gene in colorectal carcinogenesis. Acta Clin Croat, 2012, 51(1): 43-49 PMID: 22920000

[48] WuHW, GaoLD, WeiGH. hMSH2 and nm23 expression in sporadic colorectal cancer and its clinical significance. Asian Pac J Cancer Prev, 2013, 14(3): 1995-1998 PMID: 23679306

[49] YamaguchiA, UranoT, FushidaS, et al. . Inverse association of nm23-H1 expression by colorectal-cancer with liver metastasis. Br J Cancer, 1993, 68(5): 1020-1024 PMID: 8217591 PMCID: 1968746

[50] YangYQ, WuL, ChenJX, et al. . Relationship between nm23H1 genetic instability and clinical pathological characteristics in Chinese digestive system cancer patients. World J Gastroenterol, 2008, 14(36): 5549-5556 PMID: 18810774 PMCID: 2746343

[51] LinXQ, LiangY, DingSP, et al. . Genetic instability on chromosome 17q21 in gastric cancer of Chinese patients. Shi Yan Sheng Wu Xue Bao (Chinese), 2005, 38(2): 148-156

[52] ChenJ, ZhouQ, QinY, et al. . A study on the allelic deletion of nm23 genes in human lung cancer. Zhongguo Fei Ai Za Zhi, 2000, 3(1): 8-13 PMID: 20937203

[53] LuHY, ZhangGQ, LiJC. Study on genetic instability of nm23H1 gene in Chinese with original gallbladder tumor. Fen Zi Xi Bao Sheng Wu Xue Bao (Chinese), 2006, 39(3): 249-257

[54] QinZ, DaiL, TooleB, et al. . Regulation of Nm23-H1 and cell invasiveness by Kaposi’s sarcoma-associated herpesvirus. J Virol, 2011, 85(7): 3596-3606 PMID: 21270158 PMCID: 3067884

[55] MarshallJC, CollinsJ, MarinoN, et al. . The Nm23-H1 metastasis suppressor as a translational target. Eur J Cancer, 2010, 46(7): 1278-1282 PMID: 20304626 PMCID: 2858387

[56] BoissanM, LacombeML. Nm23/NDP kinases in hepatocellular carcinoma. J Bioenerg Biomembr, 2006, 38(3-4): 169-175 PMID: 16944304