Dissimilarity in gene expression profiles of lung adenocarcinoma in Japanese men and women.
BACKGROUND
Although clinical differences in lung cancer between men and women have been noted, few studies have examined the sex dissimilarity using gene expression analysis.


OBJECTIVE
The purpose of this study was to determine the different molecular carcinogenic mechanisms involved in lung cancers in Japanese men and women.


METHODS
Patients who received surgery for stage I lung adenocarcinoma were included. RNA was extracted from cancerous and normal tissue, and gene expression was then examined with oligonucleotide microarray analysis. A quantitative polymerase chain reaction assay was performed.


RESULTS
In a microarray analysis of tissue from 13 men and 6 women, 12 genes were under-expressed and 24 genes were overexpressed in lung adenocarcinoma in women compared with men. Genes related to cell cycle were present in underexpressed genes, and genes related to apoptosis, ubiquitination, and metabolism were observed in overexpressed genes. Of interest among the selected genes were WAP four-disulfide core domain 2 (WFDC2) and major histocompatibility complex, class II, DM alpha (HLA-DMA); these genes were classified into 2 groups by hierarchical clustering analysis. Expression of WFDC2 in nonsmokers was significantly higher than that in smokers (P=0.023). However, there was no significant difference in HLA-DMA expression between smokers and nonsmokers.


CONCLUSIONS
Thirty-six genes that characterize lung adenocarcinoma by sex were selected. This information may contribute to the development of novel diagnostic techniques and treatment modalities that consider sex differences in lung adenocarcinoma.
Okamoto
Junichi
J
Department of Surgery II, Nippon Medical School, Tokyo, Japan.
Onda
Masamitsu
M
Hirata
Tomomi
T
Miyamoto
Shizuyo
S
Akaishi
Junko
J
Mikami
Iwao
I
Hirai
Kyoji
K
Haraguchi
Shuji
S
Koizumi
Kiyoshi
K
Shimizu
Kazuo
K
D000230:Adenocarcinoma / Q000453:epidemiology / Q000235:genetics* / Q000378:metabolism; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007564:Japan / Q000453:epidemiology; D008175:Lung Neoplasms / Q000453:epidemiology / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D015995:Prevalence; D012334:RNA, Neoplasm / Q000235:genetics*; D012189:Retrospective Studies; D012307:Risk Factors; D012737:Sex Factors
D014408:Biomarkers, Tumor; D012334:RNA, Neoplasm