Lung cancer is the leading cause of cancer death in the United States. However, few new and effective treatments are available for lung cancer. A comprehensive understanding of the multiple signaling pathways that lead to tumor growth is a prerequisite for more effective and targeted cancer treatments. The purpose of this research was to investigate the relationship between proteins [hepatocypte growth factor (HGF), c-Met, and estrogen receptor-beta (ER-beta)] and gene expression of ER-beta (ESR2) and lung cancer survival along with identifying meaningful expression patterns of seven biomarkers [HGF, c-Met, ER-alpha, ER-beta, progesterone receptor (PR), aromatase, and epidermal growth factor receptor (EGFR)].
We used immunohistochemistry to quantify the expression of seven proteins in primary lung tumor tissues from the Lung Cancer Specialized Program of Research Excellence substudy (N=204). The generalized linear mixed model approach, which controlled for sample type (tissue microarray vs. whole-section), showed high HGF expression associated negatively with advanced cancer stage (Pglobal=0.05) and positively with smoking (Pglobal=0.14). After accounting for stage and other factors, neither HGF nor c-Met expression predicted survival.
Using a cluster algorithm, two groups were identified: (Cluster 1: high expression of ER-alpha ER-beta, cytoplasmic PR, EGFR, and aromatase; Cluster 2: high expression of HGF, c-Met, and nuclear PR). Two lung cancer subgroups exhibiting dissimilar 7-protein IHC expression patterns were similar in terms of host and tumor characteristics and in terms of overall survival (log rank test: p=0.69).
Among 22 htSNPs of ESR2 gene, we have identified that rare allele of rs1256061 is associated with the maximum ER-beta expression among patients with adenocarcinoma, but not with squamous cell carcinoma.
The results of this research enhanced the knowledge of the role of HGF and c-Met on lung cancer survival and also suggested that the relationship between genetic variation of ESR2 gene and protein expression may differ by lung cancer histology. Understanding the roles, the expression patterns, and the genetic of steroid hormones, growth factors and their receptors in lung cancer is of great public health significance because it may enable biologically directed and individually tailored treatment and their possible use as biomarkers for early detection and prevention.
| Identifer | oai:union.ndltd.org:PITT/oai:PITTETD:etd-06272010-005007 |
| Date | 29 September 2010 |
| Creators | Song, Ji Young |
| Contributors | Stephanie R. Land, Jill M. Siegfried, Joel L. Weissfeld, Brenda B. Diergaarde, Robert P. Bowser |
| Publisher | University of Pittsburgh |
| Source Sets | University of Pittsburgh |
| Language | English |
| Detected Language | English |
| Type | text |
| Format | application/pdf |
| Source | http://etd.library.pitt.edu/ETD/available/etd-06272010-005007/ |
| Rights | restricted, I hereby certify that, if appropriate, I have obtained and attached hereto a written permission statement from the owner(s) of each third party copyrighted matter to be included in my thesis, dissertation, or project report, allowing distribution as specified below. I certify that the version I submitted is the same as that approved by my advisory committee. I hereby grant to University of Pittsburgh or its agents the non-exclusive license to archive and make accessible, under the conditions specified below, my thesis, dissertation, or project report in whole or in part in all forms of media, now or hereafter known. I retain all other ownership rights to the copyright of the thesis, dissertation or project report. I also retain the right to use in future works (such as articles or books) all or part of this thesis, dissertation, or project report. |
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