Overexpression of GRO-β is associated with an unfavorable outcome in colorectal cancer

Wang,Guihua; Huang,Jianfei; Zhu,Huijun; Ju,Shaoqing; Wang,Huimin; Wang,Xudong

doi:10.3892/ol.2016.4222

Overexpression of GRO-β is associated with an unfavorable outcome in colorectal cancer

Authors:
- Guihua Wang
- Jianfei Huang
- Huijun Zhu
- Shaoqing Ju
- Huimin Wang
- Xudong Wang
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Affiliations: Center of Clinical Laboratory Medicine, Affiliated Hospital of Nantong University, Nantong, Jiangsu 226001, P.R. China, Department of Pathology, Affiliated Hospital of Nantong University, Nantong, Jiangsu 226001, P.R. China
Published online on: February 10, 2016 https://doi.org/10.3892/ol.2016.4222
Pages: 2391-2397
Copyright: © Wang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Growth-related oncogene (GRO)-β, or chemokine (C-X-C motif) ligand 2 (CXCL2), is a member of the CXC chemokine family that may mediate various functions, including attracting neutrophils to sites of inflammation, and participating in tumorigenesis and progression. However, the expression of GRO‑β in colorectal cancer (CRC) and the association with the clinical outcome of the disease remains poorly understood. In the present study, CXCL2 mRNA expression in CRC was analyzed using six independent datasets from the Oncomine microarray database. The immunohistochemical analysis of tissue microarrays (TMA) was used to characterize the expression of the GRO‑β protein in CRC. The association between GRO‑β expression and the clinicopathological features and prognosis of patients was determined by statistical analysis. The results indicated that GRO‑β was highly expressed in CRC tissues, and that high GRO‑β cytoplasmic expression was associated with the tumor location, extent of the primary tumor, and lymph node metastasis. Kaplan-Meier survival and Cox regression analysis revealed that high GRO‑β expression was an independent indicator of poor prognosis for CRC patients. The results indicate that high GRO‑β expression in CRC may correlate with an unfavorable outcome and facilitate cancer cell invasion and metastasis.

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1	Siegel R, Naishadham D and Jemal A: Cancer statistics, 2013. CA Cancer J Clin. 63:11–30. 2013. View Article : Google Scholar : PubMed/NCBI
2	Rao CV and Yamada HY: Genomic instability and colon carcinogenesis: From the perspective of genes. Front Oncol. 3:1302013. View Article : Google Scholar : PubMed/NCBI
3	Khan S, Cameron S, Blaschke M, Moriconi F, Naz N, Amanzada A, Ramadori G and Malik IA: Differential gene expression of chemokines in KRAS and BRAF mutated colorectal cell lines: Role of cytokines. World J Gastroenterol. 20:2979–2994. 2014. View Article : Google Scholar : PubMed/NCBI
4	Modi WS and Yoshimura T: Isolation of novel GRO genes and a phylogenetic analysis of the CXC chemokine subfamily in mammals. Mol Biol Evol. 16:180–193. 1999. View Article : Google Scholar : PubMed/NCBI
5	Wang D and Richmond A: Nuclear factor-kappa B activation by the CXC chemokine melanoma growth-stimulatory activity/growth-regulated protein involves the MEKK1/p38 mitogen-activated protein kinase pathway. J Biol Chem. 276:3650–3659. 2001. View Article : Google Scholar : PubMed/NCBI
6	Doll D, Keller L, Maak M, Boulesteix AL, Siewert JR, Holzmann B and Janssen KP: Differential expression of the chemokines GRO-2, GRO-3, and interleukin-8 in colon cancer and their impact on metastatic disease and survival. Int J Colorectal Dis. 25:573–581. 2010. View Article : Google Scholar : PubMed/NCBI
7	McLean MH, Murray GI, Stewart KN, Norrie G, Mayer C, Hold GL, Thomson J, Fyfe N, Hope M, Mowat NA, et al: The inflammatory microenvironment in colorectal neoplasia. PLoS One. 6:e153662011. View Article : Google Scholar : PubMed/NCBI
8	Rhodes DR, Yu J, Shanker K, Deshpande N, Varambally R, Ghosh D, Barrette T, Pandey A and Chinnaiyan AM: Large-scale meta-analysis of cancer microarray data identifies common transcriptional profiles of neoplastic transformation and progression. Proc Natl Acad Sci USA. 101:9309–9314. 2004. View Article : Google Scholar : PubMed/NCBI
9	Rhodes DR, Yu J, Shanker K, Deshpande N, Varambally R, Ghosh D, Barrette T, Pandey A and Chinnaiyan AM: ONCOMINE. A cancer microarray database and integrated data-mining platform. Neoplasia. 6:1–6. 2004. View Article : Google Scholar : PubMed/NCBI
10	Ueno H, Mochizuki H, Akagi Y, Kusumi T, Yamada K, Ikegami M, Kawachi H, Kameoka S, Ohkura Y, Masaki T, et al: Optimal colorectal cancer staging criteria in TNM classification. J Clin Oncol. 30:1519–1526. 2012. View Article : Google Scholar : PubMed/NCBI
11	Williams JR: The Declaration of Helsinki and public health. Bull World Health Organ. 86:650–652. 2008. View Article : Google Scholar : PubMed/NCBI
12	Sun R, Wang X, Zhu H, Mei H, Wang W, Zhang S and Huang J: Prognostic value of LAMP3 and TP53 overexpression in benign and malignant gastrointestinal tissues. Oncotarget. 5:12398–12409. 2014. View Article : Google Scholar : PubMed/NCBI
13	Graudens E, Boulanger V, Mollard C, Mariage-Samson R, Barlet X, Grémy G, Couillault C, Lajémi M, Piatier-Tonneau D, Zaborski P, et al: Deciphering cellular states of innate tumor drug responses. Genome Biol. 7:R192006. View Article : Google Scholar : PubMed/NCBI
14	Kaiser S, Park YK, Franklin JL, Halberg RB, Yu M, Jessen WJ, Freudenberg J, Chen X, Haigis K, Jegga AG, et al: Transcriptional recapitulation and subversion of embryonic colon development by mouse colon tumor models and human colon cancer. Genome Biol. 8:R1312007. View Article : Google Scholar : PubMed/NCBI
15	Sabates-Bellver J, Van der Flier LG, de Palo M, Cattaneo E, Maake C, Rehrauer H, Laczko E, Kurowski MA, Bujnicki JM, Menigatti M, et al: Transcriptome profile of human colorectal adenomas. Mol Cancer Res. 5:1263–1275. 2007. View Article : Google Scholar : PubMed/NCBI
16	Gaedcke J, Grade M, Jung K, Camps J, Jo P, Emons G, Gehoff A, Sax U, Schirmer M, Becker H, et al: Mutated KRAS results in overexpression of DUSP4, a MAP-kinase phosphatase, and SMYD3, a histone methyltransferase, in rectal carcinomas. Genes Chromosomes Cancer. 49:1024–1034. 2010. View Article : Google Scholar : PubMed/NCBI
17	Skrzypczak M, Goryca K, Rubel T, Paziewska A, Mikula M, Jarosz D, Pachlewski J, Oledzki J and Ostrowski J: Modeling oncogenic signaling in colon tumors by multidirectional analyses of microarray data directed for maximization of analytical reliability. PLoS One. 5:e130912010. View Article : Google Scholar : PubMed/NCBI
18	Cancer Genome Atlas Network: Comprehensive molecular characterization of human colon and rectal cancer. Nature. 487:330–337. 2012. View Article : Google Scholar : PubMed/NCBI
19	Dong QM, Zhang JQ, Li Q, Bracher JC, Hendricks DT and Zhao XH: Clinical significance of serum expression of GROβ in esophageal squamous cell carcinoma. World J Gastroenterol. 17:2658–2662. 2011. View Article : Google Scholar : PubMed/NCBI
20	Owen JD, Strieter R, Burdick M, Haghnegahdar H, Nanney L, Shattuck-Brandt R and Richmond A: Enhanced tumor-forming capacity for immortalized melanocytes expressing melanoma growth stimulatory activity/growth-regulated cytokine beta and gamma proteins. Int J Cancer. 73:94–103. 1997. View Article : Google Scholar : PubMed/NCBI
21	Buhmeida A, Bendardaf R, Hilska M, Laine J, Collan Y, Laato M, Syrjänen K and Pyrhönen S: PLA2 (group IIA phospholipase A2) as a prognostic determinant in stage II colorectal carcinoma. Ann Oncol. 20:1230–1235. 2009. View Article : Google Scholar : PubMed/NCBI
22	Saif MW and Chu E: Biology of colorectal cancer. Cancer J. 16:196–201. 2010. View Article : Google Scholar : PubMed/NCBI
23	Inoue Y, Iwata T, Okugawa Y, Kawamoto A, Hiro J, Toiyama Y, Tanaka K, Uchida K, Mohri Y, Miki C and Kusunoki M: Prognostic significance of a systemic inflammatory response in patients undergoing multimodality therapy for advanced colorectal cancer. Oncology. 84:100–107. 2013. View Article : Google Scholar : PubMed/NCBI
24	Ishizuka M, Nagata H, Takagi K, Iwasaki Y and Kubota K: Inflammation-based prognostic system predicts survival after surgery for stage IV colorectal cancer. Am J Surg. 205:22–28. 2013. View Article : Google Scholar : PubMed/NCBI
25	Dorhoi A, Iannaccone M, Farinacci M, Faé KC, Schreiber J, Moura-Alves P, Nouailles G, Mollenkopf HJ, Oberbeck-Müller D, Jörg S, et al: MicroRNA-223 controls susceptibility to tuberculosis by regulating lung neutrophil recruitment. J Clin Invest. 123:4836–4848. 2013. View Article : Google Scholar : PubMed/NCBI
26	Shang K, Bai YP, Wang C, Wang Z, Gu HY, Du X, Zhou XY, Zheng CL, Chi YY, Mukaida N and Li YY: Crucial involvement of tumor-associated neutrophils in the regulation of chronic colitis-associated carcinogenesis in mice. PLoS One. 7:e518482012. View Article : Google Scholar : PubMed/NCBI
27	Wang B, Khachigian LM, Esau L, Birrer MJ, Zhao X, Parker MI and Hendricks DT: A key role for early growth response-1 and nuclear factor-kappaB in mediating and maintaining GRO/CXCR2 proliferative signaling in esophageal cancer. Mol Cancer Res. 7:755–764. 2009. View Article : Google Scholar : PubMed/NCBI