Low Claudin-1 Expression Has Association with Deep Invading and Higher-Grade Colorectal Adenocarcinoma

Putu Erika Paskarani, Herman saputra, Ni Putu Sriwidyani, I Gusti Ayu Sri Mahendra Dewi, Luh Putu Iin Indrayani Maker, I Made Muliartha



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.



claudin-1, colorectal adenocarcinoma, prognostic factor


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.

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DOI: 10.33371/ijoc.v14i1.677

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