BUSCADOR RECOLECTA

Digital.CSIC. Repositorio Institucional del CSIC

oai:digital.csic.es:10261/330935

Supplementary Figure 1 | Identification of K-RAS most common genomic alterations in patients with NSCLC by molecular subtypes. (i) Percentage of amplifications, mutations and deletions of K-RAS gene in patients with Squamous Cell Carcinoma or Adenocarcinoma. (ii) Graphical representation of the percentage of K-RAS genomic alterations according to TCGA, Firehose Legacy and MSKCC, 2020 databases in (A) or to TCGA, PanCancer Atlas and TCGA, Firehose Legacy databases in (B). Supplementary Figure 2 | Negative correlation between the expression of upregulated genes (CLRF1, HOPX, IRS2, KIT, PDE4D, and SMOC1) and most of immune infiltrates (CD8+ T cells, Neutrophils, Macrophages and dendritic cells). A green square encircles the dots with higher expression and little infiltration level. Supplementary Figure 3 | Positive correlation between the expression of downregulated genes (CD24, CDK6, HDAC9, TIAM1, TRFC, VTRC1, and VAV3) and most of immune infiltrates (CD8+ T cells, Neutrophils, Macrophages and dendritic cells). A yellow square encircles the dots with less expression and more infiltration level. Supplementary Figure 4 | Expression of CLDN10 and TMPRSS6 in different human cancer types. Bar graph showing the expression of individual CLDN10 (in (A), TMPRSS6 in (B) or both genes combined (C) in those cancer types where expression is significantly higher in tumor samples than in normal tissue (D). No correlation between CLDN10 and TMPRSS6 gene expression with most of immune infiltrates. Supplementary Figure 5 | Higher expression of CLDN10 and TMPRSS6 in K-RAS p.G12C. (A) Table presenting 15 NSLC cell lines that present the G12C variant in K-RAS gene. Bar graph showing the expression of CLDN10 in (B), and TMPRSS6 in (C) in 92 NSLC cell lines compared to those 15 selected in A. Expression of CLDN10 in (D), and TMPRSS6 in (E) in LUAD tumor samples comparing those that harbor or not the G12C mutation. Supplementary Table 1 | Investigational and approved drugs against K-RAS identified mutations. Specific K-RAS mutation, name of the drug, status (approved or investigational), identification code (NCT) and clinical studies with links and phases are included. Intervention is included if the drug is given in combination with others. Supplementary Table 2 | Gene functions of thirteen selected deregulated genes. Supplementary Table 3 | Upregulation details of cell surface-related genes analyzed. Name of the gene, mean of expression in mutant and wildtype K-RAS tumors, fold change (FC), direction and p-value are included. Supplementary Table 4 | Kaplan-Meier survival values of cell surface-related genes. Table includes the name of the gene, the hazard ratio (HR) (in blue, significant good prognosis, and in red, bad one), p-value and fold discovery rate (FDR) for FP and in LUAD patients., Targeting K-RAS-mutant non-small cell lung cancer (NSCLC) with novel inhibitors has shown promising results with the recent approval of sotorasib in this indication. However, progression to this agent is expected, as it has previously been observed with other inhibitors. Recently, new immune therapeutics, including vectorized compounds with antibodies or modulators of the host immune response, have demonstrated clinical activity. By interrogating massive datasets, including TCGA, we identified genes that code for surface membrane proteins that are selectively expressed in K-RAS mutated NSCLC and that could be used to vectorize novel therapies. Two genes, CLDN10 and TMPRSS6, were selected for their clear differentiation. In addition, we discovered immunologic correlates of outcome that were clearly de-regulated in this particular tumor type and we matched them with immune cell populations. In conclusion, our article describes membrane proteins and immunologic correlates that could be used to better select and optimize current therapies., Peer reviewed