Low Claudin-1 Expression Has Association with Deep Invading and Higher-Grade Colorectal Adenocarcinoma
Claudin-1 is a tight junction protein in the cell that organizes paracellular permeability and epithelial polarity and maintains apical cell-to-cell adhesion. Deregulation of claudin-1 homeostasis will play pivotal role in tumorigenesis, migration, and metastasis of colorectal cancer through a complex signaling pathway. This study investigated the association of claudin-1 expression and clinicopathological factors in colorectal adenocarcinoma.
This study was a cross-sectional study of 43 colorectal cancer patients. Each clinicopathological parameter data was divided into 2 categories; depth of tumor invasion (T3, T4), degree of tumor differentiation (low, high grade), tumor location (right, left), sex (man, woman) and age (<60, ≥60 y.o). Claudin-1 expression was examined by the immunohistochemistry method and evaluated by H-Score method. The H-score cut off was determined by the mean value of 148. The difference of claudin-1 expression score with tumor depth invasion and age was analyzed by Independent t-test, and then the degree of differentiation, tumor location and sex were analyzed by Mann-Whitney. All variables were analyzed by the Chi-square analysis with a significance value of P<.05.
There was a significant mean difference of claudin-1 expression between T3 and T4 tumors (P=.041; 95% CI 1.7-75.1). Tumor with low expression of claudin-1 was 2.5 times more likely to be found in tumor with invasion depth T4 rather than T3 (P=.023; 95% CI 1.5-48). In addition, tumor with low expression of claudin-1 was 0.2 times more likely to be found in the high-grade tumor (P=.001; 95% CI 0.07-0.4). Claudin-1 expression was not statistically significant in different tumor locations, sex and age group.
There was mean difference in claudin-1 expression between T3 and T4 tumors, and between low- and high-grade tumors. The low claudin-1 expression is associated with tumor depth invasion and poorly differentiated tumors. Therefore, the use of claudin-1 as an additional prognostic factor in colorectal cancer is proposed.
Wang X, Tully O, Ngo B, Zitin M, Mullin J.M. Epithelial tight junctional changes in colorectal cancer tissue. The scientific world journal. 2011;11:826–41.
Pope, J.L, Bhat, A.A, Sharma, A, Ahmad, R, Krishnan, M, Washington, M.K, et al. Claudin-1 regulates intestinal epithelial homeostasis through the modulation of Notch-signalling. Br Med J. 2013;63(4):15–6.
Ersoz S, Mungan S, Cabanoglu U, Turgutalp H, dan Ozoran Y. Prognostic importance of Claudin-1 and Claudin-4 expression in colon carcinoma. Pathol Res Pract. 2011;97:285–9.
Leech A.O, Cruz R.G, Hill A.D, Hopkins A.M. Paradigm lost-an emerging role for over-expression of tight junction adesion proteins in cancer in cancer pathogenesis. Ann Trans Med. 2015;3(13):1–15.
Bhat A.A, Uppada S, Achkar I.W, Hashem S, Yadav S.K, Shanmugakonar M, et al. Tight junction protein and signaling pathway in cancer and inflammation: A functional crosstalk. Front Physiol. 2019;9:1–19.
Singh A.B, Uppada S.B, Dhawan P. Claudin proteins, outside-in signaling, and carcinogenesis. Eur J Physiol. 2017;469(1):69–75.
Stebbing J, Filipovic A, Giamas G. 2013. Claudin-1 as promoter of EMT in hepatocellular carcinoma. Oncogene. 2013;32:4871–72.
Kaf R, Saba E, Refaat W, Bahgat A. The Significance of Claudin-1 and S100A4 Expression in Primary Colorectal Carcinoma. Zagazig University Medical Journal. 2016;22:1–12.
Suren D, Yildirim M, Kaya V, Alikanoglu A.S, Bulbuller N, Yildiz M, et al. Loss of tight junction proteins (claudin-1,4, and 7) correlates with aggressive behavior in colorectal carcinoma. Med Sci Monit. 2014;1055–62.
Yoshida T, Kinugasa T, Akagi Y, Kawahara A, Romeo K, Siratsuchi I, et al. Decreased expression of claudin-1 in rectal cancer: A factor for reccurence and poor prognosis. Anticancer Res. 2011;31:2517–26.
Hirakawa E, Tokuhara Y, Morinishi T, Ohsaki H, Uemura E, Miki Y, et al. Down regulation of claudin-1 expression in gastric cancer mucosa is correlated with poor prognosis. Open journal of pathology. 2014;4:206–12.
Anthonysamy MA, Maker LP, Gotra IM, Saputra H. Prevalence of colorectal carcinoma based on microscopic type, sex, age and anatomic location in sanglah hospital. Intisari Sains Medis. 2018;9(2):1– 19.
Brierly JD, James DB, Gospodarowicz MK, Wittekind C. TNM Classification of malignant tumours, 8th Edition. Geneva: Union for International Cancer Control. 2017:84–87
Blanchard AA, Ma X, Dueck KJ, Penner C, Cooper SC, Mulhall D, et al. Claudin-1 expression in basal- like breast cancer is related to patient age. BMC Cancer. 2013;13(268):1–13.
Nagtegaal ID, Arends MJ, Salto-Tellez M. Colorectal adenocarcinoma. In: Lokuhetty D., White VA, Watanabe R, dan Cree IA. World Health Organization Classification of Tumours, 5th edition. France: International Agency for Research on Cancer. 2018:177–88.
Huo Q, Kinugasa T, Wang L, Huang J, Zhao J, Shibaguchi H, et al. Claudin-1 protein is a major factor involved in the tumorigenesis of colorectal cancer. Anticancer Res. 2009;29:851–8.
Skoufi U, Arvanitis DL, Lampri L, loachim E, Koutsogiannis J, Skoufi C, et al. Association of Claudin-1 with E-Cadherin/Catenin Complex, Microvessel Density (MVD)-Related Markers and Clinicopathological Feature in Colorectal Carcinoma. J Interdiscip Histopathol. 2014;2:135–44.
Hamilton SR, Bosman FT, Boffeta P, Ilyas M, Morreau H. Carcinoma of the colon and rektum. In: Hamilton S.R, Bosman F.T, Carneiro F, Hruban H.R, Theise N.D. World Health Organization Classification of Tumours, 4th edition. France: International Agency for Research on Cancer. 2010:134–5.
Article MetricsAbstract view : 110 times
PDF - 69 times
- There are currently no refbacks.
Copyright (c) 2020 Indonesian Journal of Cancer
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.