Sökning: onr:"swepub:oai:DiVA.org:uu-235148" >
Aberrantly activate...
Aberrantly activated claudin 6 and 18.2 as potential therapy targets in non-small-cell lung cancer
-
- Micke, Patrick (författare)
- Uppsala universitet,Molekylär och morfologisk patologi
-
- Mattsson, Johanna Sofia Margareta (författare)
- Uppsala universitet,Molekylär och morfologisk patologi
-
- Edlund, Karolina (författare)
- Uppsala universitet,Molekylär och morfologisk patologi
-
visa fler...
-
Lohr, Miriam (författare)
-
- Jirström, Karin (författare)
- Lund University,Lunds universitet,Tumörmikromiljö,Sektion I,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Tumor microenvironment,Section I,Department of Clinical Sciences, Lund,Faculty of Medicine
-
Berglund, Anders (författare)
-
- Botling, Johan (författare)
- Uppsala universitet,Molekylär och morfologisk patologi
-
Rahnenfuehrer, Joerg (författare)
-
- Marincevic, Millaray (författare)
- Uppsala universitet,Molekylär och morfologisk patologi
-
- Pontén, Fredrik (författare)
- Uppsala universitet,Molekylär och morfologisk patologi
-
- Ekman, Simon (författare)
- Uppsala universitet,Enheten för onkologi
-
Hengstler, Jan (författare)
-
Woell, Stefan (författare)
-
Sahin, Ugur (författare)
-
Tuereci, Oezlem (författare)
-
visa färre...
-
(creator_code:org_t)
- 2014-04-08
- 2014
- Engelska.
-
Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 135:9, s. 2206-2214
- Relaterad länk:
-
http://dx.doi.org/10...
-
visa fler...
-
https://urn.kb.se/re...
-
https://doi.org/10.1...
-
https://lup.lub.lu.s...
-
visa färre...
Abstract
Ämnesord
Stäng
- Claudins (CLDNs) are central components of tight junctions that regulate epithelial-cell barrier function and polarity. Altered CLDN expression patterns have been demonstrated in numerous cancer types and lineage-specific CLDNs have been proposed as therapy targets. The objective of this study was to assess which fraction of patients with non-small-cell lung cancer (NSCLC) express CLDN6 and CLDN18 isoform 2 (CLDN18.2). Protein expression of CLDN6 and CLDN18.2 was examined by immunohistochemistry on a tissue microarray (n=355) and transcript levels were supportively determined based on gene expression microarray data from fresh-frozen NSCLC tissues (n=196). Both were analyzed with regard to frequency, distribution and association with clinical parameters. Immunohistochemical analysis of tissue sections revealed distinct membranous positivity of CLDN6 (6.5%) and CLDN18.2 (3.7%) proteins in virtually non-overlapping subgroups of adenocarcinomas and large-cell carcinomas. Pneumocytes and bronchial epithelial cells were consistently negative. Corresponding to the protein expression, in subsets of non-squamous lung carcinoma high mRNA levels of CLDN6 (7-16%) and total CLDN18 (5-12%) were observed. Protein expression correlated well with total mRNA expression of the corresponding gene (rho=0.4-0.8). CLDN18.2 positive tumors were enriched among slowly proliferating, thyroid transcription factor 1 (TTF-1)-negative adenocarcinomas, suggesting that isoform-specific CLDN expression may delineate a specific subtype. Noteworthy, high CLDN6 protein expression was associated with worse prognosis in lung adenocarcinoma in the univariate [hazard ratio (HR): 1.8; p=0.03] and multivariate COX regression model (HR: 1.9; p=0.02). These findings encourage further clinical exploration of targeting ectopically activated CLDN expression as a valuable treatment concept in NSCLC.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
Nyckelord
- non-small-cell lung cancer
- targeted therapy
- gene expression profiling
- claudin
- tissue microarray
- non-small-cell lung cancer
- targeted therapy
- gene expression profiling
- claudin
- tissue microarray
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
Hitta via bibliotek
Till lärosätets databas
- Av författaren/redakt...
-
Micke, Patrick
-
Mattsson, Johann ...
-
Edlund, Karolina
-
Lohr, Miriam
-
Jirström, Karin
-
Berglund, Anders
-
visa fler...
-
Botling, Johan
-
Rahnenfuehrer, J ...
-
Marincevic, Mill ...
-
Pontén, Fredrik
-
Ekman, Simon
-
Hengstler, Jan
-
Woell, Stefan
-
Sahin, Ugur
-
Tuereci, Oezlem
-
visa färre...
- Om ämnet
-
- MEDICIN OCH HÄLSOVETENSKAP
-
MEDICIN OCH HÄLS ...
-
och Klinisk medicin
-
och Cancer och onkol ...
- Artiklar i publikationen
-
International Jo ...
- Av lärosätet
-
Uppsala universitet
-
Lunds universitet