A Qualitative Transcriptional Signature for the Histological Reclassification of Lung Squamous Cell carcinomas and Adenocarcinomas

Background Targeted therapy for non-small cell lung cancer is histology dependent. However, histological classification by routine pathological assessment with hematoxylin-eosin staining and immunostaining for poorly differentiated tumors, particularly those from small biopsies, is still challenging. Additionally, the effectiveness of immunomarkers is limited by technical inconsistencies of immunostaining and lack of standardization for staining interpretation. Results Using gene expression profiles of pathologically-determined lung squamous cell carcinomas and adenocarcinomas, denoted as pSCC and pADC respectively, we developed a qualitative transcriptional signature, based on the within-sample relative gene expression orderings (REOs) of gene pairs, to distinguish ADC from SCC. The signature consists of two genes, KRT5 and AGR2, which has the stable REO pattern of KRT5>AGR2 in pSCC and KRT5