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Quantitative Proteomics Indicate Radical Removal of Non-Small Cell Lung Cancer and Predict Outcome.

ABSTRACT: Non-small cell lung cancer (NSCLC) is associated with low survival rates, often due to late diagnosis and lack of personalized medicine. Diagnosing and monitoring NSCLC using blood samples has lately gained interest due to its less invasive nature. In the present study, plasma was collected at three timepoints and analyzed using proximity extension assay technology and quantitative real-time polymerase chain reaction in patients with primary NSCLC stages IA-IIIA undergoing surgery. Results were adjusted for patient demographics, tumor, node, metastasis (TNM) stage, and multiple testing. Major histocompatibility (MHC) class 1 polypeptide-related sequence A/B (MIC-A/B) and tumor necrosis factor ligand superfamily member 6 (FASLG) were significantly increased post-surgery, suggesting radical removal of cancerous cells. Levels of hepatocyte growth factor (HGF) initially increased postoperatively but were later lowered, potentially indicating radical removal of malignant cells. The levels of FASLG in patients who later died or had a relapse of NSCLC were lower at all three timepoints compared to surviving patients without relapse, indicating that FASLG may be used as a prognostic biomarker. The biomarkers were confirmed using microarray data. In conclusion, quantitative proteomics could be used for NSCLC identification but may also provide information on radical surgical removal of NSCLC and post-surgical prognosis.

SUBMITTER: Boden E

PROVIDER: S-EPMC9687227 | biostudies-literature | 2022 Oct

REPOSITORIES: biostudies-literature

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Quantitative Proteomics Indicate Radical Removal of Non-Small Cell Lung Cancer and Predict Outcome.

Bodén Embla E Andreasson Jesper J Hirdman Gabriel G Malmsjö Malin M Lindstedt Sandra S

Biomedicines 20221028 11

Non-small cell lung cancer (NSCLC) is associated with low survival rates, often due to late diagnosis and lack of personalized medicine. Diagnosing and monitoring NSCLC using blood samples has lately gained interest due to its less invasive nature. In the present study, plasma was collected at three timepoints and analyzed using proximity extension assay technology and quantitative real-time polymerase chain reaction in patients with primary NSCLC stages IA-IIIA undergoing surgery. Results were ...[more]

PMID: 36359256

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Project description:BackgroundEarly detection of small cell lung cancer (SCLC) crucially demands highly reliable markers. Growing evidence suggests that extracellular vesicles carry tumor cell-specific cargo suitable as protein markers in cancer. Quantitative proteomic profiling of circulating microvesicles and exosomes can be a high-throughput platform for discovery of novel molecular insights and putative markers. Hence, this study aimed to investigate proteome dynamics of plasma-derived microvesicles and exosomes in newly diagnosed SCLC patients to improve early detection.MethodsPlasma-derived microvesicles and exosomes from 24 healthy controls and 24 SCLC patients were isolated from plasma by either high-speed- or ultracentrifugation. Proteins derived from these extracellular vesicles were quantified using label-free mass spectrometry and statistical analysis was carried out aiming at identifying significantly altered protein expressions between SCLC patients and healthy controls. Furthermore, significantly expressed proteins were subjected to functional enrichment analysis to identify biological pathways implicated in SCLC pathogenesis.ResultsBased on fold change (FC) ≥ 2 or ≤ 0.5 and AUC ≥ 0.70 (p < 0.05), we identified 10 common and 16 and 17 unique proteins for microvesicles and exosomes, respectively. Among these proteins, we found dysregulation of coagulation factor XIII A (Log2 FC = - 1.1, p = 0.0003, AUC = 0.82, 95% CI: 0.69-0.96) and complement factor H-related protein 4 (Log2 FC = 1.2, p = 0.0005, AUC = 0.82, 95% CI; 0.67-0.97) in SCLC patients compared to healthy individuals. Our data may indicate a novel tumor-suppressing role of blood coagulation and involvement of complement activation in SCLC pathogenesis.ConclusionsIn comparing SCLC patients and healthy individuals, several differentially expressed proteins were identified. This is the first study showing that circulating extracellular vesicles may encompass specific proteins with potential diagnostic attributes for SCLC, thereby opening new opportunities as novel non-invasive markers.

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Quantitative Proteomics Indicate Radical Removal of Non-Small Cell Lung Cancer and Predict Outcome.

Publications

Quantitative Proteomics Indicate Radical Removal of Non-Small Cell Lung Cancer and Predict Outcome.

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