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Proteomic Analysis of Aberrant Protein Expression in Non-Small Cell Lung Cancer (NSCLC)

ABSTRACT: Identification of candidate biomarkers for diagnosis and prognosis of NSCLC

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Lung, Epithelial Cell Of Lung

DISEASE(S): Non-small Cell Lung Carcinoma

SUBMITTER: Baby Rorielyn Dimayacyac-Esleta

LAB HEAD: Baby Rorielyn Dimayacyac-Esleta

PROVIDER: PXD050598 | Pride | 2025-05-13

REPOSITORIES: Pride

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			Action	DRS
	20220609_Philippine_LC_TMTB03_prot_F01-R1.raw	Raw
	20220609_Philippine_LC_TMTB03_prot_F01-R2.raw	Raw
	20220609_Philippine_LC_TMTB03_prot_F02-R1.raw	Raw
	20220609_Philippine_LC_TMTB03_prot_F02-R2.raw	Raw
	20220609_Philippine_LC_TMTB03_prot_F03-R1.raw	Raw

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Publications

Discovery of Key Candidate Protein Biomarkers in Early-Stage Nonsmall Cell Lung Carcinoma through Quantitative Proteomics.

Dimayacyac-Esleta Baby Rorielyn T BRT Mira Ferdinand D FD Zarate Lorenzo M LM Porras Ben Joshua O BJO Juntilla Dave Laurence A DLA Suñga Lara Beatrice L LBL Pondevida Venus B VB Naval Sullian S SS Sayo Treah May S TMS Luna Herdee Gloriane C HGC Prieto Eloise I EI

Journal of proteome research 20250227 4

Difficulties in early-stage diagnosis are among the factors contributing to the high mortality of nonsmall cell lung carcinoma (NSCLC) patients. Unfortunately, diagnostic biomarkers are currently lacking, limiting options in the clinic. To discover proteins that have potential for biomarker applications, we performed an in-depth quantitative proteomic analysis on a cohort of Filipino early-stage NSCLC lung adenocarcinoma (LUAD) patients. Differentially expressed proteins (DEPs) were obtained by ...[more]

PMID: 40014793

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Initial Insights on the Proteomic Profile of Filipino Non-Small Cell Lung Carcinoma (NSCLC)

Project description:NSCLC remains to be the leading cause of cancer incidence and mortality in the Philippines. Early diagnosis, better understanding on the mechanisms of drug resistance, and proper treatment monitoring is necessary to lower the incidence and mortality rate of NSCLC. This study was able to provide initial insights on the proteomic profile of Filipino NSCLC by quantitative proteomic analysis and identification of aberrant expressions in the tumor tissue relative to the adjacent normal tissue specimen. A total of 4518 proteins were identified and from this, 1855 proteins were found to be significantly upregulated and downregulated. Functional and pathway analysis was done to the upregulated and downregulated proteins with at least 4-fold expression change. Pathway analysis revealed the possible activation of the upregulated protein, MUC1, which is a known oncogenic driver involved in the stimulation of pathways that promote angiogenesis in NSCLC tumor, and prevention of apoptosis. STAT1 and STAT3, also found upregulated in the tumor specimen, were known to have interactions with MUC1 which results to expression of proteins for cell proliferation. The analysis also suggests the stabilization of HIF which allows cell growth in the hypoxic tumor environment, and the activation of EIF signaling correlated with low survival rate of NSCLC patients. Our data demonstrate the rich proteomic information that can be obtained from comprehensive profiling of the NSCLC proteome and applications for better understanding of NSCLC tumorigenicity.

2022-02-10 | PXD027710 | Pride

MicroRNA expression data from H1299 cells

Project description:We explored the biological effects of AGO2 downregulation on the expression of miRNAs in human NSCLC cells. Using AGO2 siRNA as a positive control, we overexpressed miR-138 in H1299 cells to observe changes in the miRNA profile using an miRNA microarray assay. Total RNAs were extracted from H1299 cells transfected with NC, AGO2 siRNA or miR-138 for 48h. Their microRNAs expression profiles were investigated using LCSciences Human miRNA Array platform (LCSciences, Houston, TX; Sanger mirBase Release 19.0).

2015-06-05 | E-GEOD-69561 | biostudies-arrayexpress

NSCLC Lung Adenocarcinoma Proteomics

Project description:Alterations in cellular antigen processing and presenting machinery has gained increased interest as a hallmark of cancer-related inflammation. Growing evidence suggest that proteasome composition and immunoproteasome expression can influence the efficacy of cancer therapies. By applying proteasome foot-printing to clinical samples of Non Small Cell lung Cancer (NSCLC), we found tumor specific alterations in degradation products and increased expression of the proteasome regulator, PA200. We show that increased levels of PA200 alter the cleavage specificities of proteasomal-cleaved peptides and reduce antigenicity. We found that smoking-induced expression of PA200 abrogated immunoproteasome activity and is associated with poor survival. As immunotherapy is becoming a common treatment of NSCLC, we hypothesized that PA200 expression may contribute to resistance mechanism to immunotherapy. Consistent with this possibility, we found that the ratio between PA200 and the immunoproteasome subunit PSMB10, and not their absolute levels, were significantly associated with poor response to Durvalamab. Induced reduction in PA200 in vivo was associated with increased immune infiltration and attenuated tumor growth.

2023-03-30 | PXD019573 | Pride

Cytotoxic mechanisms of pemetrexed and HDAC inhibition in non-small cell lung cancer cells involving ribonucleotides in DNA

Project description:The cytotoxic mechanisms of thymidylate synthase inhibitors, such as the multitarget antifolate pemetrexed, are not yet fully understood. Emerging evidence indicates that combining pemetrexed with histone deacetylase inhibitors (HDACi) may enhance therapeutic efficacy in non-small cell lung cancer (NSCLC). To explore this further, A549 NSCLC cells were treated with various combinations of pemetrexed and the HDACi MS275 (Entinostat), and subsequently assessed for cell viability, cell cycle changes, and genotoxic markers. Proteomic alterations were analyzed using label-free shotgun and targeted LC–MS/MS. MS275 enhanced the sensitivity of A549 cells to pemetrexed, but only when administered following prior treatment with pemetrexed. Both HeLa (p53 negative) and A549 (p53 positive) showed robust activation of γH2AX upon treatment with this combination. Importantly, CRISPR/Cas9 knockout of the uracil-DNA glycosylase UNG did not affect γH2AX activation or sensitivity to pemetrexed. Proteomic analysis revealed that MS275 altered the expression of known pemetrexed targets, as well as several proteins involved in pyrimidine metabolism and DNA repair, which could potentiate pemetrexed cytotoxicity. Contrary to the conventional model of antifolate toxicity, which implicates futile cycles of uracil incorporation and excision in DNA, we propose that ribonucleotide incorporation in nuclear and mitochondrial DNA significantly contributes to the cytotoxicity of antifolates like pemetrexed, and likely also of fluorinated pyrimidine analogs. HDAC inhibition apparently exacerbates cytotoxicity of these agents by inhibiting error-free repair of misincorporated ribonucleotides in DNA. The potential of HDACis to modulate pyrimidine metabolism and DNA damage responses offers novel strategies for improving NSCLC outcomes.

2024-12-18 | PXD051824 | Pride

Transcriptomic profiling of immune and stromal cells from the non small cell lung cancer (NSCLC) environment

Project description:T lymphocytes can efficiently counteract the growth of tumors within the tumor microenvironment. Specialized immune-interacting fibroblasts, termed fibroblastic reticular cells (FRC) are responsible for the formation of specialized niches promoting immune cell activation in secondary lymphoid organs and originate from embryonic progenitors. FRCs have also been identified in tertiary lymphoid structures (TLS) in tumor tissues. However, the identity and differentiation of TLS-associated FRC subsets that promote intra-tumoral T cell activity have remained unexplored. Here, we employed single cell RNA-sequencing of fibroblasts and immune cells, sampled from subpleural margin, central margin and unaffected lung tissue in non small cell lung cancer (NSCLC), demonstrating the formation of specific tumor T cell environments (TTEs) underpinned by CCL19-expressing FRCs. We detected tumor-specific FRC subsets namely CCL19-expressing TRCs and perivascular reticular cells (PRCs) interacting with intratumoral T cells, and thus regulating FRC differentiation and T cell activation. Our results highlight a remarkable functionality of FRCs to efficiently determine protective antitumoral T cell responses in NSCLC.

2024-11-19 | E-MTAB-13710 | biostudies-arrayexpress

Next Generation Sequencing Facilitates Quantitative Analysis of Wild Type and snf[148] ovary Transcriptomes

Project description:Comparison of wild type and tumorous ovaries reveals that tumors inappropriately express a large number of testis genes mRNA profiles of ovaries from 0-24 hour virgin wild type (WT) and 3 day old snf[148] females were generated by deep sequencing, in duplicate, using Illumina HiSeq 2500.

2015-02-17 | E-GEOD-65932 | biostudies-arrayexpress

Transcriptomic analysis of patient-derived resected lung NSCLC cells (part 2)

Project description:To identify genes encoding cell surface proteins that are preferentially expressed in NSCLC cells, CD45-CD31-EpCAM+ cells were purified by FACS from either tumor regions or unaffected regions in resected lung tissues from patients with NSCLC, then subjected to RNA sequencing analysis.

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Transcriptomic analysis of patient-derived resected lung NSCLC cells (part 1)

2024-08-05 | GSE226772 | GEO

LC-MSMS of the MHC-I immunopeptidome of human NSCLC samples

Project description:While immune checkpoint blockade (ICB) therapy has significantly improved the outcome of metastatic melanoma and non-small cell lung cancer (NSCLC), most patients do not derive long-term benefits. Previous studies suggest that treatment failure is partly due to insufficient immune recognition of tumor antigens (TAs). Notably, immune targeting of TAs has focused on TAs derived from non-synonymous genomic mutations. We used a proteogenomic approach combining RNA-sequencing and mass spectrometry to study the MHC I-immunopeptidome of cutaneous melanoma and NSCLC samples. The RNA-sequencing of each sample was used to construct sample-specific databases for the mass spectrometry-based identification of MHC I-associated peptides (MAPs). MAPs were then filtered based on their RNA expression in the respective cancer types from The Cancer Genome Atlas (TCGA-SKCM for melanoma MAPs, or TCGA-LUSC and TCGA-LUAD for NSCLC MAPs) vs. benign tissues (from the Genotype-Tissue Expression (GTEx) Project, medullary thymic epithelial cells, purified blood and bone marrow cells, and normal melanocytes for melanoma or bronchial brushing samples for NSCLC). MAPs were classified as mutated tumor-specific antigens (mTSAs, derived from non-synonymous mutations expressed in the sample of origin), or unmutated tumor antigens: aberrantly expressed tumor-specific antigens (aeTSAs, no/low expression in benign tissues and at least two times higher expression in TCGA), tumor-associated antigens (TAAs, significant expression in benign tissues and at least two times higher expression in TCGA), lineage-associated antigens (LSAs, specific expression to cancer and normal tissue of origin, i.e., lung and bronchial brushing samples for NSCLC or skin and melanocytes for melanoma). The tumor antigens described here represent attractive targets for immunotherapy of melanoma and NSCLC.

2025-02-19 | PXD043057 | Pride

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