Can gene expression profiling predict survival for patients with squamous cell carcinoma of the lung?
BACKGROUND
Lung cancer remains to be the leading cause of cancer death worldwide. Patients with similar lung cancer may experience quite different clinical outcomes. Reliable molecular prognostic markers are needed to characterize the disparity. In order to identify the genes responsible for the aggressiveness of squamous cell carcinoma of the lung, we applied DNA microarray technology to a case control study. Fifteen patients with surgically treated stage I squamous cell lung cancer were selected. Ten were one-to-one matched on tumour size and grade, age, gender, and smoking status; five died of lung cancer recurrence within 24 months (high-aggressive group), and five survived more than 54 months after surgery (low-aggressive group). Five additional tissues were included as test samples. Unsupervised and supervised approaches were used to explore the relationship among samples and identify differentially expressed genes. We also evaluated the gene markers' accuracy in segregating samples to their respective group. Functional gene networks for the significant genes were retrieved, and their association with survival was tested.


RESULTS
Unsupervised clustering did not group tumours based on survival experience. At p < 0.05, 294 and 246 differentially expressed genes for matched and unmatched analysis respectively were identified between the low and high aggressive groups. Linear discriminant analysis was performed on all samples using the 27 top unique genes, and the results showed an overall accuracy rate of 80%. Tests on the association of 24 gene networks with study outcome showed that 7 were highly correlated with the survival time of the lung cancer patients.


CONCLUSIONS
The overall gene expression pattern between the high and low aggressive squamous cell carcinomas of the lung did not differ significantly with the control of confounding factors. A small subset of genes or genes in specific pathways may be responsible for the aggressive nature of a tumour and could potentially serve as panels of prognostic markers for stage I squamous cell lung cancer.
Sun
Zhifu
Z
Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota 55905, USA. sun.zhifu@mayo.edu <sun.zhifu@mayo.edu>
Yang
Ping
P
Aubry
Marie-Christine
MC
Kosari
Farhad
F
Endo
Chiaki
C
Molina
Julian
J
Vasmatzis
George
G
D002294:Carcinoma, Squamous Cell / Q000175:diagnosis / Q000235:genetics / Q000401:mortality*; D016022:Case-Control Studies; D016000:Cluster Analysis; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D008175:Lung Neoplasms / Q000175:diagnosis / Q000235:genetics / Q000401:mortality*; D008297:Male; D020411:Oligonucleotide Array Sequence Analysis; D011379:Prognosis; D016019:Survival Analysis