A Four-Gene Signature from NCI-60 Cell Line for Survival Prediction in Non–Small Cell Lung Cancer

Abstract

Purpose: Metastasis is the main cause of mortality in non-small cell lung cancer (NSCLC) patients. Genes that can discriminate the invasion ability of cancer cells may become useful candidates for clinical outcome prediction. We identify invasion-associated genes through computational and laboratorial approach that supported this idea in NSCLC. Experimental Design: We first conducted invasion assay to characterize the invasion abilities of NCI-60 lung cancer cell lines. We then systematically exploited NCI-60 microarray databases to identify invasion-associated genes that showed differential expression between the high and the low invasion cell line groups. Furthermore, using the microarray data of Duke lung cancer cohort (GSE 3141), invasion-associated genes with good survival prediction potentials were obtained. Finally, we validated the findings by conducting quantitative PCR assay on an in-house collected patient group (n = 69) and by using microarray data from two public western cohorts (n = 257 and 186). Results: The invasion-associated four-gene signature (ANKRD49, LPHN1, RABAC1, and EGLN2) had significant prediction in three validation cohorts (P = 0.0184, 0.002, and 0.017, log-rank test). Moreover, we showed that four-gene signature was an independent prognostic factor (hazard ratio, 2.354, 1.480, and 1.670; P = 0.028, 0.014, and 0.033), independent of other clinical covariates, such as age, gender, and stage. Conclusion: The invasion-associated four-gene signature derived from NCI-60 lung cancer cell lines had good survival prediction power for NSCLC patients. (Clin Cancer Res 2009;15(23):7309-15)

Population differences in microRNA expression and biological implications

“…38,39 ANKRD49 was identified as one of the 4 non-small cell lung cancer invasion-associated gene signatures, which can independently predict prognosis regardless of age, gender and stage of disease. 40 miR-30b was found to be downregulated in squamous cell lung carcinoma compared with normal lung tissue. 41 It is also downregulated in multiple myeloma, 42 in invasive urothelial carcinoma of the bladder, 43 in polycythemia vera (a colonal hematopoietic stem cell disorder) reticulocytes.…”

Global microRNA Analysis of the NCI-60 Cancer Cell Panel

“…Recently, the metastatic potential of the NCI-60 lung cancer cells was measured in Matrigel and an mRNA signature was found that correlated to overall survival (37). By applying the same split (into a low and high metastatic potential group), we identified a short list of miRNAs (Table 2) which could separate high from low metastatic potential cell lines.…”

Expression Profiles of Loneliness-associated Genes for Survival Prediction in Cancer Patients

“…Differing from these works, our latest approach started with an in silicon exploitation of the public domain microarray databases to derive the gene signature and concluded with validation by public independent clinical data (Hsu et al, 2009;Guo and Wan 2012).…”

“…In fact our results of survival prediction showed the 34-gene signature derived from loneliness-associated genes was suit for survival prediction in cancer patients, and it was as good as the gene signature derived from other biological methods, eg. the metastatic cells approach in paper (Hsu et al, 2009).…”

“…In breast cancer, Motakis et al, used a couple of genes for survival prediction (Motakis et al, 2009). Two articles derived the survival significant genes and implemented Cox proportional hazards model to predict survival between high-risk and low-risk patients in non-small cell lung cancer (Hsu et al, 2009;Hou et al, 2010). Yoshihara et al, derived 88 survival significant genes for predicting survival in ovarian cancer (Yoshihara et al, 2010).…”