CXCR4 and MMP-9 Immunoexpression are Associated with Metastasis in Infiltrating Urothelial Carcinoma of The Bladder

Siska Dwiyantie Wahyuni, Sri Suryanti, Hasrayati Agustina, Bethy Suryawathy Hernowo

Abstract


Background: Infiltrating urothelial carcinoma of the bladder (IUCB) is an aggressive urinary tract cancer. Most of the patients were diagnosed with advanced stages, and many have metastasized. Metastasis is responsible for 90% of cancer deaths compared to the primary tumor itself. In previous research, the expression of CXCR4 and MMP-9 has been suggested to correlate with metastasis and prognosis in several cancers. This study aimed to analyze the association of CXCR4 and MMP-9 expression with metastasis in infiltrating urothelial carcinoma of the bladder.

Methods: This cross-sectional study included 40 selected paraffin-embedded tissue blocks from histopathologically diagnosed IUCB patients, consisting of 20 cases of non-metastasizing and 20 cases of metastasizing IUCB. Immunohistochemical staining for CXCR4 and MMP-9 was performed in all cases. All data were analyzed using the Chi-Square test with p < 0.05 of a significant level and then processed using SPSS 24.0 for Windows.

Results: High CXCR4 immunoexpression was found in 18 (45%) of all cases, and high MMP-9 immunoexpression was found in 19 (47.5%) cases. High immunoexpression of CXCR4 and MMP9 in infiltrating urothelial carcinoma of the bladder showed significant association with metastasis (p < 0.05). The stepwise logistic regression analysis revealed that both CXCR-4 and MMP-9 immunoexpressions were independent prognostic factors for metastasis.

Conclusions: CXCR4 and MMP-9 play a role in the metastatic process in infiltrating urothelial carcinoma of the bladder.


Keywords


CXCR4, infiltrating urothelial carcinoma of the bladder, metastasis, MMP-9

References


Saginala K, Barsouk A, Aluru JS, Rawla P, Padala SA, Barsouk A. Epidemiology of Bladder Cancer. Med Sci (Basel). 2020 Mar 13;8(1).

Zeng FC, Cen S, Tang ZY, Kang XL. Elevated matrix metalloproteinase-9 expression may contribute to the pathogenesis of bladder cancer. Oncology letters. 2016 Mar;11(3):2213-22.

Furusato B, Mohamed A, Uhlén M, Rhim JS. CXCR4 and cancer. Pathology international. 2010 Jul;60(7):497-505.

Walenkamp AME, Lapa C, Herrmann K, Wester H-J. CXCR4 Ligands: The Next Big Hit? 2019.

Salem N, Kamal I, Al-Maghrabi J, Adel Abuzenadah AAP-Z, Yousif Qari, Mahmoud Al-Ahwal, Mohammed Al-Qahtani & Abdelbaset Buhmeida. High expression of matrix metalloproteinases: MMP-2 and MMP-9 predicts poor survival outcome in colorectal carcinoma. 2016.

Liu X, Su C, Xu J, Zhou D, Yan H, Li W, et al. Immunohistochemical analysis of matrix metalloproteinase-9 predicts papillary thyroid carcinoma prognosis. Oncology letters. 2019 Feb;17(2):2308-16.

Cai X, Zhu H, Li Y. PKCζ, MMP‑2 and MMP‑9 expression in lung adenocarcinoma and association with a metastatic phenotype. Mol Med Rep. 2017 Dec;16(6):8301-6.

Zhao S, Wang J, Qin C. Blockade of CXCL12/CXCR4 signaling inhibits intrahepatic cholangiocarcinoma progression and metastasis via inactivation of canonical Wnt pathway. J Exp Clin Cancer Res. 2014 Dec 4;33(1):103.

Weigel MT, Krämer J, Schem C, Wenners A, Alkatout I, Jonat W, et al. Differential expression of MMP-2, MMP-9 and PCNA in endometriosis and endometrial carcinoma. Eur J Obstet Gynecol Reprod Biol. 2012 Jan;160(1):74-8.

Wahyuni SD, Suryanti S, Agustina H, Hernowo B. The Association of Clinicopathological Features with Metastatic Status in Infiltrative Urothelial Carcinoma of Bladder. Journal of Drug Delivery and Therapeutics. 2020;10(6-s):99-02.

Otsuka S, Bebb G. The CXCR4/SDF-1 Chemokine Receptor Axis: A New Target Therapeutic for Non-small Cell Lung Cancer. Journal of Thoracic Oncology. 2008 2008/12/01/;3(12):1379-83.

Liao Y ZC, Zeng H, Zuo D, Wang ZY, Yin F, Hua Y and Cai Z: . The role of the CXCL12-CXCR4/CXCR7 axis in the progression and metastasis of bone sarcomas (Review). Int J Mol Med 2013;32: :1239-46.

Wang H, Yang D, Wang K, Wang J. Expression and potential role of chemokine receptor CXCR4 in human bladder carcinoma cell lines with different metastatic ability. Mol Med Rep. 2011 May-Jun;4(3):525-8.

Retz MM, Sidhu SS, Blaveri E, Kerr SC, Dolganov GM, Lehmann J, et al. CXCR4 expression reflects tumor progression and regulates motility of bladder cancer cells. 2004.

Miao C, Liang C, Zhu J, Xu A, Zhao K, Hua Y, et al. Prognostic role of matrix metalloproteinases in bladder carcinoma: a systematic review and meta-analysis. Oncotarget. 2017 May 9;8(19):32309-21.

Yao Z, Yuan T, Wang H, Yao S, Zhao Y, Liu Y, et al. MMP-2 together with MMP-9 overexpression correlated with lymph node metastasis and poor prognosis in early gastric carcinoma. Tumour Biol. 2017 Jun;39(6):1010428317700411.

Wu QW, Yang QM, Huang YF, She HQ, Liang J, Yang QL, et al. Expression and clinical significance of matrix metalloproteinase-9 in lymphatic invasiveness and metastasis of breast cancer. PLoS One. 2014;9(5):e97804.


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DOI: 10.33371/ijoc.v16i3.892

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