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Supplemental Figure Legends from Lung Squamous Cell Carcinomas with Basaloid Histology Represent a Specific Molecular Entity

Supplementary Table Legend, Supplementary References, Supplementary Information

Supplemental Table 1:A. Characteristics of the antibodies used for immunohistochemical measures B.Clinical characteristics of the CIT cohort of patients. Supplemental Table 2: A .Gene expression related statistics in the CIT cohort. B. immunohistochemistry quickscore measures of SOX4 and IVL and prediction of the basaloid satus Supplemental Table 3: Gene signatures and pathways deregulation analysis in histological subtypes. Supplemental Table 4: DNA copy number aberrations related statistics in the CIT cohort. Supplemental Table 5: 139-gene centroids used for prediction of the CIT molecular subtypes. Supplemental Table 6: Molecular subtype prediction and survival data for each sample of the CIT and 8 validation datasets. Supplemental Table 7: Gene signatures and pathways enrichment analysis in molecular subtypes in the CIT cohort and 4 validation datasets.

Purpose: The basaloid carcinoma (pure) and the (mixed) basaloid variant of lung squamous cell carcinoma (SCC) have a dismal prognosis but their underlying specific molecular characteristics remain obscure and no therapy has proven to be efficient.Experimental Design: To assess their molecular specificity among other lung SCCs we analyzed DNA copy number aberrations and mRNA expression pangenomic profiles of 93 SCCs, including 42 basaloid samples (24 pure, 18 mixed).Results: Supervised analyses reveal that pure basaloid tumors display a specific mRNA expression profile, encoding factors controlling the cell cycle, transcription, chromatin, and splicing, with prevalent expression in germline and stem cells, while genes related to squamous differentiation are underexpressed. From this signature, we derived a 2-genes (SOX4, IVL) immunohistochemistry-based predictor that discriminated basaloid tumors (pure and mixed) from non-basaloid tumors with 94% accuracy in an independent series. The pure basaloid tumors are also distinguished through unsupervised analyses. Using a centroid-based predictor, the corresponding molecular subtype was found in 8 independent public datasets (n = 58/533), and was shown to be associated with a very poor survival as compared with other SCCs (adjusted HR = 2.45; P = 0.000001).Conclusion: This study enlightens the heterogeneity of SCCs that can be subclassified in mRNA expression subtypes. This study demonstrates for the first time that basaloid SCCs constitute a distinct histomolecular entity, which justifies its recognition and distinction from non-basaloid SCCs. In addition, their characteristic molecular profile highlights their intrinsic resistance to cytotoxic chemotherapy and could serve as a guide for targeted therapies. Clin Cancer Res; 20(22); 5777–86. ©2014 AACR.

Supplemental Figure 1: Embryonic stem cell-like gene expression signatures in Basaloid tumors. Supplemental Figure 2: DNA copy number aberrations in the CIT cohort. Supplementary Figure 3: Consensus classification of the expression profiles of tumor samples in the CIT cohort. Supplemental Figure 4: Kaplan-Meier curves in the CIT cohort according to CIT molecular subtypes. Supplemental Figure 5: Kaplan-Meier curves of overall survival in 7 validation public datasets according to CIT molecular subtypes and Wilkerson et al. subtypes.

Purpose: The basaloid carcinoma (pure) and the (mixed) basaloid variant of lung squamous cell carcinoma (SCC) have a dismal prognosis but their underlying specific molecular characteristics remain obscure and no therapy has proven to be efficient. Experimental Design: To assess their molecular specificity among other lung SCCs we analyzed DNA copy number aberrations and mRNA expression pangenomic profiles of 93 SCCs, including 42 basaloid samples (24 pure, 18 mixed). Results: Supervised analyses reveal that pure basaloid tumors display a specific mRNA expression profile, encoding factors controlling the cell cycle, transcription, chromatin, and splicing, with prevalent expression in germline and stem cells, while genes related to squamous differentiation are underexpressed. From this signature, we derived a 2-genes (SOX4, IVL) immunohistochemistry-based predictor that discriminated basaloid tumors (pure and mixed) from non-basaloid tumors with 94% accuracy in an independent series. The pure basaloid tumors are also distinguished through unsupervised analyses. Using a centroid-based predictor, the corresponding molecular subtype was found in 8 independent public datasets (n = 58/533), and was shown to be associated with a very poor survival as compared with other SCCs (adjusted HR = 2.45; P = 0.000001). Conclusion: This study enlightens the heterogeneity of SCCs that can be subclassified in mRNA expression subtypes. This study demonstrates for the first time that basaloid SCCs constitute a distinct histomolecular entity, which justifies its recognition and distinction from non-basaloid SCCs. In addition, their characteristic molecular profile highlights their intrinsic resistance to cytotoxic chemotherapy and could serve as a guide for targeted therapies. Clin Cancer Res; 20(22); 5777–86. ©2014 AACR.