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. 2013 Jul 1:13:322.
doi: 10.1186/1471-2407-13-322.

Chemokine (C-X-C) ligand 1 (CXCL1) protein expression is increased in aggressive bladder cancers

Makito Miyake  1 , Adrienne Lawton, Steve Goodison, Virginia Urquidi, Evan Gomes-Giacoia, Ge Zhang, Shanti Ross, Jeongsoon Kim, Charles J Rosser
Affiliations

Chemokine (C-X-C) ligand 1 (CXCL1) protein expression is increased in aggressive bladder cancers

Makito Miyake et al. BMC Cancer. .

Abstract

Background: Chemokines, including chemokine (C-X-C motif) ligand 1 (CXCL1), may regulate tumor epithelial-stromal interactions that facilitate tumor growth and invasion. Studies have linked CXCL1 expression to gastric, colon and skin cancers, but limited studies to date have described CXCL1 protein expression in human bladder cancer (BCa).

Methods: CXCL1 protein expression was examined in 152 bladder tissue specimens (142 BCa) by immunohistochemical staining. The expression of CXCL1 was scored by assigning a combined score based on the proportion of cells staining and intensity of staining. CXCL1 expression patterns were correlated with clinicopathological features and follow-up data.

Results: CXCL1 protein expression was present in cancerous tissues, but was entirely absent in benign tissue. CXCL1 combined immunostaining score was significantly higher in high-grade tumors relative to low-grade tumors (p = 0.012). Similarly, CXCL1 combined immunostaining score was higher in high stage tumors (T2-T4) than in low stage tumors (Ta-T1) (p < 0.0001). An increase in the combined immunostaining score of CXCL1 was also associated with reduced disease-specific survival.

Conclusion: To date, this is the largest study describing increased CXCL1 protein expression in more aggressive phenotypes in human BCa. Further studies are warranted to define the role CXCL1 plays in bladder carcinogenesis and progression.

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Figures

Figure 1
Figure 1
Expression of CXCL1 protein in human bladder. Representative staining of benign bladder tissue A, bladder cancer B, and tumor-adjacent normal urothelia within section with cancer C. All images were captured at 200× or 400× magnification.
Figure 2
Figure 2
Expression of CXCL1 protein in high-grade and high stage human bladder cancer. A, Representative staining of low-grade bladder tumor and high-grade bladder tumor. Bar graph illustrates combined immunostaining score for CXCL1 expression according to tumor grade. B, Representative staining of non-muscle invasive bladder cancer (pT1) and muscle invasive bladder cancer (pT3). Bar graph illustrates combined immunostaining score for CXCL1 expression according to tumor stage. All images were captured at 400× magnification. *, p < 0.01 and ***, p < 0.0001.
Figure 3
Figure 3
Probability of bladder cancer specific survival according to CXCL1 staining patterns. ‘High’ combined immunostaing score for CXCL1 was associated with a significant reduction in (A) disease-specific survival and (B) overall survival (Log-rank test).
Figure 4
Figure 4
CXCL1 mRNA expression in human bladder cancer from publically available datasets. Three public datasets containing transcriptome profiles of bladder tumor tissues were obtained and analyzed for CXCL1 expression using Oncomine 3.0. Mean relative mRNA levels for CXCL1 in muscle invasive bladder cancer cases was significantly elevated compared to non-muscle invasive bladder cancer cases (Sanchez-Carbayo et al., p = 1.72-6[28], Dyrskjot et al. p = 3.77-6[29], and Lee et al., p = 1.12-4[30]).
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