Prognostic value of CXCL17 and CXCR8 expression in patients with colon cancer

Yao,Hongyan; Lv,Yufeng; Bai,Xuefeng; Yu,Zhaojin; Liu,Xiaojian

doi:10.3892/ol.2020.11819

Prognostic value of CXCL17 and CXCR8 expression in patients with colon cancer

Authors:
- Hongyan Yao
- Yufeng Lv
- Xuefeng Bai
- Zhaojin Yu
- Xiaojian Liu
View Affiliations

Affiliations: Department of Pharmacology, School of Basic Medical Sciences, Jinzhou Medical University, Jinzhou, Liaoning 121001, P.R. China, Department of Respiration and Critical Care, The Affiliated Hongqi Hospital of Mudanjiang Medical University, Mudanjiang, Heilongjiang 157011, P.R. China, Department of Pharmacology, School of Pharmacy, China Medical University, Shenyang, Liaoning 110001, P.R. China
Published online on: July 7, 2020 https://doi.org/10.3892/ol.2020.11819
Pages: 2711-2720
Copyright: © Yao et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

C‑X‑C motif chemokine ligand 17 (CXCL17) is a mucous chemokine and its expression is highly correlated with that of G protein‑coupled receptor 35 (GPR35), which has been confirmed as its receptor and named C‑X‑C motif chemokine receptor 8 (CXCR8). CXCL17 is upregulated in several types of cancer. However, the biological role of this chemokine in colon cancer remains unknown. In the present study, the expression levels of CXCL17 and CXCR8 were examined using immunohistochemistry in 101 colon cancer tissues and 79 healthy tumour‑adjacent tissues. CXCL17 and CXCR8 expression levels were increased in the colon cancer samples compared with tumour‑adjacent samples. Patients with high CXCL17 expression had longer overall survival (OS) compared with patients with low expression of CXCL17 (log‑rank test; P=0.027). However, CXCR8 expression, but not CXCL17, was an independent prognostic factor for OS in patients with colon cancer. The expression of CXCR8 correlated positively with that of CXCL17 in colon cancer samples (ρ=0.295; P=0.003). Furthermore, the combined high expression of CXCL17 and CXCR8 was a significant independent prognostic factor for OS in patients with colon cancer (P=0.001). In subgroups with a TNM stage of I‑II, the patients with combined high expression of CXCL17 and CXCR8 had a longer survival compared with those without combined high expression (P=0.001). However, this difference was not observed in subgroups with a TNM stage of III‑IV. Collectively, these findings suggest that CXCL17/CXCR8 signalling may be involved in colon cancer and contribute to improved patient outcomes.

View Figures

View References

1	Sokol CL and Luster AD: The chemokine system in innate immunity. Cold Spring Harb Perspect Biol. 7:a0163032015. View Article : Google Scholar : PubMed/NCBI
2	Rotondi M, Chiovato L, Romagnani S, Serio M and Romagnani P: Role of chemokines in endocrine autoimmune diseases. Endocr Rev. 28:492–520. 2007. View Article : Google Scholar : PubMed/NCBI
3	Raman D, Baugher PJ, Thu YM and Richmond A: Role of chemokines in tumor growth. Cancer Lett. 256:137–165. 2007. View Article : Google Scholar : PubMed/NCBI
4	Weinstein EJ, Head R, Griggs DW, Sun D, Evans RJ, Swearingen ML, Westlin MM and Mazzarella R: VCC-1, a novel chemokine, promotes tumor growth. Biochem Biophys Res Commun. 350:74–81. 2006. View Article : Google Scholar : PubMed/NCBI
5	Pisabarro MT, Leung B, Kwong M, Corpuz R, Frantz GD, Chiang N, Vandlen R, Diehl LJ, Skelton N, Kim HS, et al: Cutting edge: Novel human dendritic cell- and monocyte-attracting chemokine-like protein identified by fold recognition methods. J Immunol. 176:2069–2073. 2006. View Article : Google Scholar : PubMed/NCBI
6	Burkhardt AM, Tai KP, Flores-Guiterrez JP, Vilches-Cisneros N, Kamdar K, Barbosa-Quintana O, Valle-Rios R, Hevezi P, Zuñiga J, Selman M, et al: CXCL17 is a mucosal chemokine elevated in idiopathic pulmonary fibrosis that exhibits broad antimicrobial activity. J Immunol. 188:6399–6406. 2012. View Article : Google Scholar : PubMed/NCBI
7	Hernández-Ruiz M and Zlotnik A: Mucosal chemokines. J Interferon Cytokine Res. 37:62–70. 2017. View Article : Google Scholar : PubMed/NCBI
8	Matsui A, Yokoo H, Negishi Y, Endo-Takahashi Y, Chun NA, Kadouchi I, Suzuki R, Maruyama K, Aramaki Y, Semba K, et al: CXCL17 expression by tumor cells recruits CD11b+Gr1 high F4/80-cells and promotes tumor progression. PLoS One. 7:e440802012. View Article : Google Scholar : PubMed/NCBI
9	Saghir FS, Rose IM, Dali AZ, Shamsuddin Z, Jamal AR and Mokhtar NM: Gene expression profiling and cancer-related pathways in type I endometrial carcinoma. Int J Gynecol Cancer. 20:724–731. 2010. View Article : Google Scholar : PubMed/NCBI
10	Mu X, Chen Y, Wang S, Huang X, Pan H and Li M: Overexpression of VCC-1 gene in human hepatocellular carcinoma cells promotes cell proliferation and invasion. Acta Biochim Biophysica Sinica. 41:631–637. 2009. View Article : Google Scholar
11	Ohlsson L, Hammarström ML, Lindmark G, Hammarstrom S and Sitohy B: Ectopic expression of the chemokine CXCL17 in colon cancer cells. Br J Cancer. 114:697–703. 2016. View Article : Google Scholar : PubMed/NCBI
12	Hiraoka N, Yamazaki-Itoh R, Ino Y, Mizuguchi Y, Yamada T, Hirohashi S and Kanai Y: CXCL17 and ICAM2 are associated with a potential anti-tumor immune response in early intraepithelial stages of human pancreatic carcinogenesis. Gastroenterology. 140:310–321. 2011. View Article : Google Scholar : PubMed/NCBI
13	Mao Y, Zhao Q, Yin S, Ding X and Wang H: Genome-wide expression profiling and bioinformatics analysis of deregulated genes in human gastric cancer tissue after gastroscopy. Asia Pac J Clin Oncol. 14:e29–e36. 2018. View Article : Google Scholar : PubMed/NCBI
14	Maravillas-Montero JL, Burkhardt AM, Hevezi PA, Carnevale CD, Smit MJ and Zlotnik A: Cutting edge: GPR35/CXCR8 is the receptor of the mucosal chemokine CXCL17. J Immunol. 194:29–33. 2015. View Article : Google Scholar : PubMed/NCBI
15	Guo YJ, Zhou YJ, Yang XL, Shao ZM and Ou ZL: The role and clinical significance of the CXCL17-CXCR8 (GPR35) axis in breast cancer. Biochem Biophys Res Commun. 493:1159–1167. 2017. View Article : Google Scholar : PubMed/NCBI
16	Khandelwal AR, Alam MM, Moore-Medlin T, Savage HA and Nathan CAO: Role of the CXCL17-CXCR8 (GPR35) axis in cutaneous squamous cell carcinoma. Cancer Res. 792019.PubMed/NCBI
17	Lan YT, Yang SH, Chang SC, Liang WY, Li AF, Wang HS, Jiang JK, Chen WS, Lin TC and Lin JK: Analysis of the seventh edition of american joint committee on colon cancer staging. Int J Colorectal Dis. 27:657–663. 2012. View Article : Google Scholar : PubMed/NCBI
18	Liu X, Xiao Q, Bai X, Yu Z, Sun M, Zhao H, Mi X, Wang E, Yao W, Jin F, et al: Activation of STAT3 is involved in malignancy mediated by CXCL12-CXCR4 signaling in human breast cancer. Oncol Rep. 32:2760–2768. 2014. View Article : Google Scholar : PubMed/NCBI
19	Wang W, Han T, Tong W, Zhao J and Qiu X: Overexpression of GPR35 confers drug resistance in NSCLC cells by β-arrestin/Akt signaling. Onco Targets Ther. 11:6249–6257. 2018. View Article : Google Scholar : PubMed/NCBI
20	Rashad Y, Olsson L, Israelsson A, Öberg Å, Lindmark G, Hammarström ML, Hammarström S and Sitohy B: Lymph node CXCL17 messenger RNA: A new prognostic biomarker for colon cancer. Tumour Biol. 40:10104283187992512018. View Article : Google Scholar : PubMed/NCBI
21	Ali H, AbdelMageed M, Olsson L, Israelsson A, Lindmark G, Hammarström ML, Hammarström S and Sitohy B: Utility of G protein-coupled receptor 35 expression for predicting outcome in colon cancer. Tumour Biol. 41:10104283198588852019. View Article : Google Scholar : PubMed/NCBI
22	Wang L, Li H, Zhen Z, Ma X, Yu W, Zeng H and Li L: CXCL17 promotes cell metastasis and inhibits autophagy via the LKB1-AMPK pathway in hepatocellular carcinoma. Gene. 690:129–136. 2019. View Article : Google Scholar : PubMed/NCBI
23	Li L, Yan J, Xu J, Liu CQ, Zhen ZJ, Chen HW, Ji Y, Wu ZP, Hu JY, Zheng L and Lau WY: CXCL17 expression predicts poor prognosis and correlates with adverse immune infiltration in hepatocellular carcinoma. PLoS One. 9:e1100642014. View Article : Google Scholar : PubMed/NCBI
24	Wang X, Deavers M, Patenia R, Bassett RL Jr, Mueller P, Ma Q, Wang E and Freedman RS: Monocyte/macrophage and T-cell infiltrates in peritoneum of patients with ovarian cancer or benign pelvic disease. J Transl Med. 4:302006. View Article : Google Scholar : PubMed/NCBI
25	Walczak K, Dabrowski W, Langner E, Zgrajka W, Piłat J, Kocki T, Rzeski W and Turski WA: Kynurenic acid synthesis and kynurenine aminotransferases expression in colon derived normal and cancer cells. Scand J Gastroenterol. 46:903–912. 2011. View Article : Google Scholar : PubMed/NCBI
26	Oka S, Ota R, Shima M, Yamashita A and Sugiura T: GPR35 is a novel lysophosphatidic acid receptor. Biochem Biophys Res Commun. 395:232–237. 2010. View Article : Google Scholar : PubMed/NCBI
27	Binti Mohd Amir NAS, Mackenzie AE, Jenkins L, Boustani K, Hillier MC, Tsuchiya T, Milligan G and Pease JE: Evidence for the Existence of a CXCL17 receptor distinct from GPR35. J Immunol. 201:714–724. 2018. View Article : Google Scholar : PubMed/NCBI
28	Park SJ, Lee SJ, Nam SY and Im DS: GPR35 mediates lodoxamide-induced migration inhibitory response but not CXCL17-induced migration stimulatory response in THP-1 cells; is GPR35 a receptor for CXCL17? Br J Pharmacol. 175:154–161. 2018. View Article : Google Scholar : PubMed/NCBI