ORIGINAL ARTICLE
Claudin 6 is associated with a short survival and a short recurrent free interval in non-small cell lung carcinoma
1
Department of Pathology and Forensic Medicine, Institute of Clinical Medicine, Pathology and Forensic Medicine, School of Medicine, University of Eastern Finland, Cancer Center of Eastern Finland, Kuopio, Finland
2
Department of Pathology, North Karelia Central Hospital, Joensuu, Finland
3
Department of Pathology, Sapporo Medical University School of Medicine, Sapporo, Japan
Submission date: 2022-02-23
Acceptance date: 2022-02-27
Publication date: 2022-06-28
Pol J Pathol 2022;73(1):1-5
KEYWORDS
TOPICS
ABSTRACT
We investigated the expression of claudin 6 in non-small-cell lung carcinomas (NSCLC) by immunohistochemistry.
Samples of 164 patients with NSCLC were studied by immunohistochemistry.
Claudin 6 was expressed in 42 % of cases. Its expression was significantly more frequent in adeno- than in squamous cell carcinoma (p = 0.002). There was no association between the TNM status and claudin 6 expression. Claudin 6 associated with a poor prognosis of the patients and with a short recurrence-free interval (p = 0.002, p < 0.001). The association with survival had independent prognostic value (p = 0.011).
The results show that claudin 6 can be regarded as a marker of poor prognosis in lung cancer. This is different to some other cancers, such as breast and cervical carcinoma suggesting that claudin 6 probably induces other cellular pathways in neoplastic lung cells than in those tumors. In lung cancer, adenocarcinomas were most abundantly positive indicating a higher linkage of claudin 6 to glandular differentiation.
Samples of 164 patients with NSCLC were studied by immunohistochemistry.
Claudin 6 was expressed in 42 % of cases. Its expression was significantly more frequent in adeno- than in squamous cell carcinoma (p = 0.002). There was no association between the TNM status and claudin 6 expression. Claudin 6 associated with a poor prognosis of the patients and with a short recurrence-free interval (p = 0.002, p < 0.001). The association with survival had independent prognostic value (p = 0.011).
The results show that claudin 6 can be regarded as a marker of poor prognosis in lung cancer. This is different to some other cancers, such as breast and cervical carcinoma suggesting that claudin 6 probably induces other cellular pathways in neoplastic lung cells than in those tumors. In lung cancer, adenocarcinomas were most abundantly positive indicating a higher linkage of claudin 6 to glandular differentiation.
REFERENCES (25)
1.
Osanai M, Takasawa A, Murata M, Sawada N. Claudins in cancer: bench to bedside. Pflugers Arch. 2017; 469: 55-67.
2.
Krug SM, Günzel D, Conrad MP, et al. Charge-selective claudin channels. Ann N Y Acad Sci. 2012; 1257: 20-28.
3.
Gonçalves A, Ambrósio AF, Fernandes R. Regulation of claudins in blood-tissue barriers under physiological and pathological states. Tissue Barriers 2013; 1: e24782.
4.
Soini Y, Kinnula V, Kahlos K, Pääkkö P. Claudins in differential diagnosis between mesothelioma and metastatic adenocarcinoma of the pleura. J Clin Pathol 2006; 59: 250-254.
5.
Soini Y. Expression of claudins 1, 2, 3, 4, 5 and 7 in various types of tumours. Histopathology 2005; 46: 551-560.
6.
Wang L, Jin X, Lin D, et al. Clinicopathologic significance of claudin-6, occludin, and matrix metalloproteinases -2 expression in ovarian carcinoma. Diagn Pathol 2013; 8: 190.
7.
Lin Z, Zhang X, Liu Z, et al. The distinct expression patterns of claudin-2, -6, and -11 between human gastric neoplasms and adjacent non-neoplastic tissues. Diagn Pathol 2013; 8: 133.
8.
Sullivan LM, Yankovich T, Le P, et al. Claudin-6 is a nonspecific marker for malignant rhabdoid and other pediatric tumors. Am J Surg Pathol 2012; 36: 73-80.
9.
Liu Y, Jin X, Li Y, Ruan Y, et al. DNA methylation of claudin-6 promotes breast cancer cell migration and invasion by recruiting MeCP2 and deacetylating H3Ac and H4Ac. J Exp Clin Cancer Res 2016; 35: 120.
10.
Guo Y, Xu X, Liu Z, et al. Apoptosis signal-regulating kinase 1 is associated with the effect of claudin-6 in breast cancer. Diagn Pathol 2012; 7: 111.
11.
Xu X, Jin H, Liu Y, et al. The expression patterns and correlations of claudin-6, methy-CpG binding protein 2, DNA methyltransferase 1, histone deacetylase 1, acetyl-histone H3 and acetyl-histone H4 and their clinicopathological significance in breast invasive ductal carcinomas. Diagn Pathol 2012; 7: 33.
12.
Wang Q, Zhang Y, Zhang T, et al. Low claudin-6 expression correlates with poor prognosis in patients with non-small cell lung cancer. Onco Targets Ther 2015; 8: 1971-1977.
13.
Micke P, Mattsson JS, Edlund K, et al. Aberrantly activated claudin 6 and 18.2 as potential therapy targets in non-small-cell lung cancer. Int J Cancer 2014; 135: 2206-2214.
14.
Wang L, Xue Y, Shen Y, et al. Claudin 6: a novel surface marker for characterizing mouse pluripotent stem cells. Cell Res 2012; 22: 1082-1085.
15.
Jimenez FR, Lewis JB, Belgique ST, et al. Developmental lung expression and transcriptional regulation of claudin-6 by TTF-1, Gata-6, and FoxA2. Respir Res 2014; 15: 70.
16.
Sugimoto K, Ichikawa-Tomikawa N, Satohisa S, et al. The tight-junction protein claudin-6 induces epithelial differentiation from mouse F9 and embryonic stem cells. PLoS One 2013; 8: e75106.
17.
Kojima M, Sugimoto K, Tanaka M, et al. Prognostic significance of aberrant claudin-6 expression in endometrial cancer. Cancers 2020; 12: 2748.
18.
Yu S, Zhang Y, Li Q, et al. CLDN6 promotes tumor progression through the YAP1-snail1 axis in gastric cancer. Cell Death Dis 2019; 10: 949.
19.
Yu M, Chen Y, Li X, et al. YAP1 contributes to NSCLC invasion and migration by promoting Slug transcription via the transcription co-factor TEAD. Cell Death Dis 2018; 9: 464.
20.
Song P, Li Y, Dong Y, et al. Estrogen receptor β inhibits breast cancer cells migration and invasion through CLDN6-mediated autophagy. J Exp Clin Cancer Res 2019; 38: 354.
21.
Li X, Li H, Liu C, et al. CLDN6-mediates SB431542 action through MMPs to regulate the invasion, migration, and EMT of breast cancer cells. Int J Clin Exp Pathol 2020; 13: 1590-1600.
22.
Zhang X, Ruan Y, Li Y, et al. Expression of apoptosis signal-regulating kinase 1 is associated with tight junction protein claudin-6 in cervical carcinoma. Int J Clin Exp Pathol 2015; 8: 5535-5541.
23.
Lechpammer M, Resnick MB, Sabo E, et al. The diagnostic and prognostic utility of claudin expression in renal cell neoplasms. Mod Pathol 2008; 21: 1320-1329.
24.
Soini Y, Tommola S, Helin H, Martikainen P. Claudins 1, 3, 4 and 5 in gastric carcinoma, loss of claudin expression associates with the diffuse subtype. Virchows Arch 2006; 448: 52-58.
25.
Turksen K, Troy TC. Permeability barrier dysfunction in transgenic mice overexpressing claudin 6. Development 2002; 129: 1775-1784.
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| eISSN: | 2084-9869 |
| ISSN: | 1233-9687 |
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