Hsu Y.-C.Yuan S.-S.Chen H.-Y.SUNG-LIANG YULiu C.-H.Hsu P.-Y.Wu G.Lin C.-H.Chang G.-C.Li K.-C.PAN-CHYR YANG2020-12-022020-12-0220091078-0432https://www.scopus.com/inward/record.uri?eid=2-s2.0-73249132249&doi=10.1158%2f1078-0432.CCR-09-1572&partnerID=40&md5=646ad098ea03a1a3649c49f7d118ac37https://scholars.lib.ntu.edu.tw/handle/123456789/523686Purpose: 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. ? 2009 American Association for Cancer Research.[SDGs]SDG3ankr49 gene; article; cancer cell culture; cancer invasion; cancer survival; cohort analysis; DNA microarray; egln2 gene; gene; human; human cell; human tissue; lphn1 gene; lung non small cell cancer; major clinical study; metastasis potential; priority journal; rabac1 gene; reverse transcription polymerase chain reaction; Carcinoma, Non-Small-Cell Lung; Cell Line, Tumor; Cell Survival; Cohort Studies; Collagen; Computational Biology; Databases, Genetic; Drug Combinations; Humans; Laminin; Lung Neoplasms; Neoplasm Invasiveness; Neoplasm Metastasis; Oligonucleotide Array Sequence Analysis; Prognosis; Proportional Hazards Models; Proteoglycans; Treatment Outcomejournal article10.1158/1078-0432.CCR-09-1572199201082-s2.0-73249132249