Extracellular Matrix Alterations in Low Grade Lung Adenocarcinoma Compared to Normal Lung Tissue by Imaging Mass Spectrometry

Details

• Alternative Title:
  J Mass Spectrom
• Personal Author:
  Angel, Peggi M. ; Bruner, Evelyn ; Bethard, Jennifer ; Clift, Cassandra L. ; Ball, Lauren ; Drake, Richard R. ; Feghali-Bostwick, Carol
• Description:
  Lung adenocarcinoma (LUAD) is the second most common cancer, affecting both men and women. Fibrosis is a hallmark of LUAD occurring throughout progression with excess production of extracellular matrix (ECM) components that lead to metastatic cell processes. Understanding the ECM cues that drive LUAD progression has been limited due to a lack of tools that can access and report on ECM components within the complex tumor microenvironment. Here, we test whether low-grade LUAD can be distinguished from normal lung tissue using a novel ECM imaging mass spectrometry (ECM IMS) approach. ECM IMS analysis of a tissue microarray with 20 low-grade LUAD tissues and 20 normal lung samples from 10 patients revealed 25 peptides that could discriminate between normal and low-grade LUAD using area under the receiver-operating curve (AUC) ≥0.7, P value ≤.001. Principal component analysis demonstrated that 62.4% of the variance could be explained by sample origin from normal or low-grade tumor tissue. Additional work performed on a wedge resection with moderately differentiated LUAD demonstrated that the ECM IMS analytical approach could distinguish LUAD spectral features from spectral features of normal adjacent lung tissue. Conventional liquid chromatography with tandem mass spectrometry (LC-MS/MS) proteomics demonstrated that specific sites of hydroxylation of proline (HYP) were a main collagen post translational modification that was readily detected in LUAD. A distinct peptide from collagen 3A1 modified by HYP was increased 3.5 fold in low-grade LUAD compared with normal lung tissue (AUC 0.914, P value <.001). This suggests that regulation of collagen proline hydroxylation could be an important process during early LUAD fibrotic deposition. ECM IMS is a useful tool that may be used to define fibrotic deposition in low-grade LUAD.
• Subjects:
  Adenocarcinoma Of Lung Adult Area Under Curve Chromatography, Liquid Collagen Extracellular Matrix Female Humans Hydroxylation Lung Neoplasms Male Matrix Metalloproteinase 13 Middle Aged Proline Proof Of Concept Study Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization Tandem Mass Spectrometry Tissue Array Analysis Tumor Microenvironment

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• Keywords:
  Adenocarcinoma Collagen Extracellular Matrix Formalin-fixed Imaging Mass Spectrometry Lung Cancer MALDI Imaging Mass Spectrometry Paraffin-embedded Tissue Imaging Peptide Imaging Proteomics Tissue Imaging

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• Source:
  J Mass Spectrom. 55(4):e4450
• Pubmed ID:
  31654589
• Pubmed Central ID:
  PMC7145762
• Document Type:
  Journal Article
• Funding:
  P30 DK123704/DK/NIDDK NIH HHSUnited States/ ; S10 OD025126/CD/ODCDC CDC HHSUnited States/ ; S10 OD010731/CD/ODCDC CDC HHSUnited States/ ; HL007260/HB/NHLBI NIH HHSUnited States/ ; S10 OD010731/OD/NIH HHSUnited States/ ; T32 HL007260/HL/NHLBI NIH HHSUnited States/ ; S10 OD025126/OD/NIH HHSUnited States/ ; South Carolina Centers of Economic Excellence SmartState Program/ ; P20GM103542/GM/NIGMS NIH HHSUnited States/ ; P30 CA138313/CA/NCI NIH HHSUnited States/ ; P20 GM103542/GM/NIGMS NIH HHSUnited States/
• Volume:
  55
• Issue:
  4
• Collection(s):
  CDC Public Access
• Main Document Checksum:
  urn:sha256:0d5c43f5f7f2d7c1c53e20882cee14fc611a982faf819cad19693c665bbb7484
• Download URL:
  https://stacks.cdc.gov/view/cdc/86642/cdc_86642_DS1.pdf
• File Type:
  [PDF - 3.50 MB ]