Additional file 1 of mTOR pathway gene mutations predict response to immune checkpoint inhibitors in multiple cancers
Creators: name: Cheng, Lei
name: Wang, Yanan
name: Qiu, Lixin
name: Chang, Yuanyuan
name: Lu, Haijiao
name: Liu, Chenchen
name: Zhang, Bo
name: Zhou, Yan
name: Bai, Hao
name: Xiong, Liwen
name: Zhong, Hua
name: Nie, Wei
name: Han, Baohui
Publisher: name: figshare
Year: 2022
Subjects: subject: Immunology
subject: FOS: Clinical medicine

description: Additional file 1: Figure S1. Mutation types of mTOR pathway and survival of patients with ICI treatment. The association of the missense mutations and other mutations in mTOR pathway with survival patients who underwent ICI treatment, respectively (A-B). The validation for this association stratified by mutation types (C-D). Visualization in discovery (E) and validation (F) for the multivariate survival analysis in overall patients, missense mutation carriers, and other mutation carriers. Figure S2. Mutation frequency change of the DNA damage response pathway genes in presence of mutations in the 8-gene signature of mTOR pathway. The change of mutation frequency for each gene in DNA repair pathways in presence of the 8-gene signature mutation. Analysis was performed in TCGA (A) and was validated in MSKCC study (B), with frequency changes expressed as logarithmic ratio (mutant-type signature/wild-type signature patients). logarithmic P value indicated the level of significance, and those above the dashed line indicated statistical significance. Figure S3. Mutations and the activation status of mTOR pathway. Target gene of key mTOR pathway complement, including mTORC1 and mTORC2 (B). The association between the mutations in the 8-gene signature and mRNA expression of the target genes in response to mTOR pathway. Figure S4. Validation of the pathway enrichment analysis using transcriptome data from IMvigor210 clinical trial. Pathway enrichment analysis from IMvigor210 clinical trial using GSEA method, in the comparison of mutant-type versus wild-type patients for the 8-gene signature involved in mTOR pathway. We showed representative pathway enrichment involved in cancer immunity (A). All pathways enriched was summarized in one figure (B). We also summarized the enriched pathways overlapped with TCGA database using venn diagram and listed the overlapped in details (C). Figure S5. One clinical case with AKT1 mutation have good response to ICI treatment. An 82-year-old man with advanced squamous cell carcinoma of the lung was tested to have AKT1 mutation in tumors upon transbronchil biopsy. The tumor had shrunk by roughly two thirds after 2 cycle treatment of 200 mg pembrolizumab, as indicated by computed tomography images of plain film (A), mediastinal window (B) and pulmonary window (C). Figure S6. mTOR pathway mutations in circulating free DNA (cfDNA) and ICI treatment. Blood-based NGS was performed in OAK and POPLAR trial with comparison of ICI treatment versus chemotherapy, which was extracted for the mutation states of the 8-gene signature involved in mTOR pathway. The outcome comparison of atezolizumab versus docetaxel in patients with the 8-gene signature mutations in cfDNA, in terms of OS (A), PFS (B), and ORR (C) and DCB rate (D). Figure S7. The treatment outcome of patients with mTOR pathway mutations in circulating free DNA (cfDNA) in the subgroups stratified by TMB. The OS and PFS comparison of atezolizumab versus docetaxel in patients with the 8-gene signature mutations involved in mTOR pathway in cfDNA, with subgroup analysis in low-TMB patients (A-B) and high-TMB patients (C-D), respectively.