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CD99 is a novel prognostic stromal marker in non-small cell lung cancer

Edlund, Karolina; Lindskog, Cecilia; Saito, Akira; Berglund, Anders; Ponten, Fredrik; Goransson-Kultima, Hanna; Isaksson, Anders; Jirström, Karin LU ; Planck, Maria and Johansson, Leif LU , et al. (2012) In International Journal of Cancer 131(10). p.2264-2273
Abstract
The complex interaction between cancer cells and the microenvironment plays an essential role in all stages of tumourigenesis. Despite the significance of this interplay, alterations in protein composition underlying tumourstroma interactions are largely unknown. The aim of this study was to identify stromal proteins with clinical relevance in non-small cell lung cancer (NSCLC). A list encompassing 203 stromal candidate genes was compiled based on gene expression array data and available literature. The protein expression of these genes in human NSCLC was screened using the Human Protein Atlas. Twelve proteins were selected that showed a differential stromal staining pattern (BGN, CD99, DCN, EMILIN1, FBN1, PDGFRB, PDLIM5, POSTN, SPARC,... (More)
The complex interaction between cancer cells and the microenvironment plays an essential role in all stages of tumourigenesis. Despite the significance of this interplay, alterations in protein composition underlying tumourstroma interactions are largely unknown. The aim of this study was to identify stromal proteins with clinical relevance in non-small cell lung cancer (NSCLC). A list encompassing 203 stromal candidate genes was compiled based on gene expression array data and available literature. The protein expression of these genes in human NSCLC was screened using the Human Protein Atlas. Twelve proteins were selected that showed a differential stromal staining pattern (BGN, CD99, DCN, EMILIN1, FBN1, PDGFRB, PDLIM5, POSTN, SPARC, TAGLN, TNC and VCAN). The corresponding antibodies were applied on tissue microarrays, including 190 NSCLC samples, and stromal staining was correlated with clinical parameters. Higher stromal expression of CD99 was associated with better prognosis in the univariate (p = 0.037) and multivariate (p = 0.039) analysis. The association was independent from the proportion of tumour stroma, the fraction of inflammatory cells and clinical and pathological parameters like stage, performance status and tumour histology. The prognostic impact of stromal CD99 protein expression was confirmed in an independent cohort of 240 NSCLC patients (p = 0.008). Furthermore, double-staining confocal fluorescence microscopy showed that CD99 was expressed in stromal lymphocytes as well as in cancer-associated fibroblasts. Based on a comprehensive screening strategy the membrane protein CD99 was identified as a novel stromal factor with clinical relevance. The results support the concept that stromal properties have an important impact on tumour progression. (Less)
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published
subject
keywords
CD99, CAF, tumour stroma, gene expression, lung cancer, tissue, microarray
in
International Journal of Cancer
volume
131
issue
10
pages
2264 - 2273
publisher
John Wiley & Sons
external identifiers
  • wos:000309185300007
  • scopus:84867063079
ISSN
0020-7136
DOI
10.1002/ijc.27518
language
English
LU publication?
yes
id
075685b4-c15a-4bd4-8a53-ece6d03435a3 (old id 3189565)
date added to LUP
2012-12-03 07:09:11
date last changed
2017-08-20 03:05:29
@article{075685b4-c15a-4bd4-8a53-ece6d03435a3,
  abstract     = {The complex interaction between cancer cells and the microenvironment plays an essential role in all stages of tumourigenesis. Despite the significance of this interplay, alterations in protein composition underlying tumourstroma interactions are largely unknown. The aim of this study was to identify stromal proteins with clinical relevance in non-small cell lung cancer (NSCLC). A list encompassing 203 stromal candidate genes was compiled based on gene expression array data and available literature. The protein expression of these genes in human NSCLC was screened using the Human Protein Atlas. Twelve proteins were selected that showed a differential stromal staining pattern (BGN, CD99, DCN, EMILIN1, FBN1, PDGFRB, PDLIM5, POSTN, SPARC, TAGLN, TNC and VCAN). The corresponding antibodies were applied on tissue microarrays, including 190 NSCLC samples, and stromal staining was correlated with clinical parameters. Higher stromal expression of CD99 was associated with better prognosis in the univariate (p = 0.037) and multivariate (p = 0.039) analysis. The association was independent from the proportion of tumour stroma, the fraction of inflammatory cells and clinical and pathological parameters like stage, performance status and tumour histology. The prognostic impact of stromal CD99 protein expression was confirmed in an independent cohort of 240 NSCLC patients (p = 0.008). Furthermore, double-staining confocal fluorescence microscopy showed that CD99 was expressed in stromal lymphocytes as well as in cancer-associated fibroblasts. Based on a comprehensive screening strategy the membrane protein CD99 was identified as a novel stromal factor with clinical relevance. The results support the concept that stromal properties have an important impact on tumour progression.},
  author       = {Edlund, Karolina and Lindskog, Cecilia and Saito, Akira and Berglund, Anders and Ponten, Fredrik and Goransson-Kultima, Hanna and Isaksson, Anders and Jirström, Karin and Planck, Maria and Johansson, Leif and Lambe, Mats and Holmberg, Lars and Nyberg, Fredrik and Ekman, Simon and Bergqvist, Michael and Landelius, Per and Lamberg, Kristina and Botling, Johan and Ostman, Arne and Micke, Patrick},
  issn         = {0020-7136},
  keyword      = {CD99,CAF,tumour stroma,gene expression,lung cancer,tissue,microarray},
  language     = {eng},
  number       = {10},
  pages        = {2264--2273},
  publisher    = {John Wiley & Sons},
  series       = {International Journal of Cancer},
  title        = {CD99 is a novel prognostic stromal marker in non-small cell lung cancer},
  url          = {http://dx.doi.org/10.1002/ijc.27518},
  volume       = {131},
  year         = {2012},
}