Reduced XPC messenger RNA level may predict a poor outcome of patients with nonsmall cell lung cancer.
BACKGROUND
Homologous deletion of the xeroderma pigmentosum complementary group C (XPC) repair gene frequently causes lung adenocarcinoma in mice, suggesting that an XPC defect may play a critical role in lung tumorigenesis. The current study attempted to determine whether reduced XPC mRNA levels predict the clinical outcome of lung cancer patients.


METHODS
XPC, p27(kip) (cdk inhibitory protein), and S-phase kinase-associated protein (skp2) levels were evaluated by Western blot analysis in a series of lung cancer cell lines with different invasive abilities. Migration and invasive abilities were measured using a modified Boyden chamber without and with Matrigel, respectively. To test whether XPC affects cell invasive ability, XPC gene protein expression was reduced in low invasive cells by RNA interference (RNAi) and assayed with Boyden chamber. XPC mRNA levels in 126 nonsmall cell lung cancers (NSCLCs) were examined by real-time-reverse-transcriptase polymerase chain reaction (RT-PCR). The prognostic value of XPC mRNA expression was statistically analyzed by the Kaplan-Meier method and Cox proportional hazards regression.


RESULTS
The expression of XPC was reduced with increasing invasive potential in CL1-series lung cancer cell lines. When the XPC level was reduced by RNAi, cell migration and invasiveness increased markedly; the increased invasiveness may be caused by decreased expression of p27(kip) and increased expression of skp2 and E2F transcription factor 1. To determine whether reduced XPC expression was correlated with tumor aggressiveness and poor patient survival, XPC mRNA levels were evaluated by real-time RT-PCR. Kaplan-Meier analysis demonstrated that the median survival of patients with lower XPC mRNA levels was shorter compared with patients with higher XPC mRNA levels (P = .0440). Cox regression analysis further indicated that XPC mRNA level may act as an independent prognostic factor for NSCLC patients (P = .014).


CONCLUSIONS
The results of the current study suggest that reduced XPC mRNA level may constitute an independent prognostic factor for NSCLC patients.
Wu
Yi-Hui
YH
Institute of Medical and Molecular Toxicology, Chung Shan Medical University, Taichung, Taiwan, Republic of China.
Cheng
Ya-Wen
YW
Chang
Jinghua Tsai
JT
Wu
Tzu-Chin
TC
Chen
Chih-Yi
CY
Lee
Huei
H
D000368:Aged; D015153:Blotting, Western; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D045744:Cell Line, Tumor; D002465:Cell Movement; D050760:Cyclin-Dependent Kinase Inhibitor p27; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D005260:Female; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D011237:Predictive Value of Tests; D011379:Prognosis; D016016:Proportional Hazards Models; D034622:RNA Interference; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000706:statistics & numerical data; D044786:S-Phase Kinase-Associated Proteins / Q000378:metabolism
C436291:CDKN1B protein, human; D004268:DNA-Binding Proteins; D047908:Intracellular Signaling Peptides and Proteins; D012333:RNA, Messenger; D044786:S-Phase Kinase-Associated Proteins; D050760:Cyclin-Dependent Kinase Inhibitor p27; C086984:XPC protein, human