Integrative Proteomic Characterization of Human Lung Adenocarcinoma

Abstract

Highlights d Discovery of prognosis-associated proteins and pathways at early stage of LUAD d Proteomics revealed three subtypes related to clinical and molecular features d Identification of subtype-specific kinases and cancerassociated phosphoproteins d Identification of potential prognostic biomarkers and drug targets in LUAD

Proteomic Analyses Identify Differentially Expressed Proteins and Pathways Between Low-Risk and High-Risk Subtypes of Early-Stage Lung Adenocarcinoma and Their Prognostic Impacts

“…More recently, three major proteomic/proteogenomic studies integrated proteome, transcriptome and genome sequencing data of LUAD and delineated the molecular signature of its pathogenesis and progression. Xu et al revealed three subtypes of LUAD related to clinical and molecular features based on proteomic clustering and potential drug targets were investigated as well (12). Gillette et al identified by guest on December 6, 2020 multi-omic clusters and immune subtypes of LUAD using comprehensive proteogenomic data.…”

Integrative Analysis of Membrane Proteome and MicroRNA Reveals Novel Lung Cancer Metastasis Biomarkers

“…The complex regulatory landscape of cancer metastasis underscores the need of integrative approaches in cancer research. Multi-omics computational studies are an active area of investigation and perform analysis of genomic, proteomic, and transcriptional data combined with prior knowledge of regulatory relationships to uncover clinically relevant discovery such as biomarkers, therapeutically targets, and outcome prediction (Liu et al, 2017;Jiang et al, 2019;Xu et al, 2020). One such recently proposed method -the Tied Diffusion Through Interacting Events (TieDIE) algorithm uses a network diffusion approach to connect genomic perturbations to transcriptional changes (Paull et al, 2013).…”

Combined Methylome and Transcriptome Analyses Reveals Potential Therapeutic Targets for EGFR Wild Type Lung Cancers with Low PD-L1 Expression

“…Protein products of 9 DMEGs were identified as drug interacting ( Table 3 ). The majority of these, including XDH (Xanthine Dehydrogenase) [ 35 , 36 ], ATIC (5-Aminoimidazole-4-Carboxamide Ribonucleotide Formyltransferase/IMP Cyclohydrolase) [ 37 ], CA9 (Carbonic Anhydrase 9) [ 38 ], SLC7A11 (Solute Carrier Family 7 Member 11) [ 39 ], and GAPDH (Glyceraldehyde-3-Phosphate Dehydrogenase) [ 40 ] are implicated in tumorigenesis. XDH, which encodes for xanthine dehydrogenase, has been reported to be highly expressed in a lung adenocarcinoma (LUAD) subtype associated with poor survival [ 36 ].…”

“…Of the 5 drugs targeting SLC7A11, riluzole, a noncompetitive metabotropic glutamate receptor 1 (mGluR1) antagonist, and sulfasalazine, a cystine/glutamate antiporter system xc-inhibitor used to treat inflammatory bowel disease and arthritis, have antitumor properties [ 48 , 49 , 50 ]. Most recently, GAPDH has been identified as a potential prognostic biomarker or drug target of LUAD in a comprehensive proteomics analysis conducted by Jun-Yu Xu et al [ 40 ]. In our study, GAPDH was hypomethylated in gene body and was associated with up-regulated gene expression, and also found as a drug interacting target.…”

“…We used DMEGs protein–drug interaction data to identify potential therapeutic candidates from DrugBank database. Remarkably, our analysis identified the drug target GAPDH, which has just been identified as a potential prognostic biomarker or drug target of LUAD in a comprehensive proteomics analysis on LUAD patients [ 40 ]. Besides, we identified pemetrexed, the only drug currently approved by the FDA for first-line use in combination with anti-PD1 antibodies against lung cancer regardless of PD-L1 expression [ 7 , 8 , 9 ], which indicated that our finding drugs may enrich the library of candidates for combination strategies based on immune checkpoint inhibitors.…”