Serum Proteomic Profiling Reveals Differentially Expressed IGHG3 and A1AG1 as Potential Predictors of Chemotherapeutic Response in Advanced Non-small Cell Lung Cancer

Anticancer Res. 2021 Apr;41(4):1871-1882. doi: 10.21873/anticanres.14953.

Abstract

Background: This study aimed to identify differentially expressed proteins in the serum of advanced non-small cell lung cancer (NSCLC) patients responding to carboplatin (CAR) plus paclitaxel (PTX) chemotherapy compared to non-responders.

Materials and methods: Serum from 8 responders and 6 non-responders was subjected to proteomic analysis by label-free liquid chromatography tandem mass spectrometry and validated by western blotting. CAR/PTX-resistant human H1792 and A549 cells were used for evaluating gene expression.

Results: Fifty-two proteins were differentially expressed between responders and non-responders. Alpha 1 antitrypsin antibody, alpha 1 acid glycoprotein (A1AG1), afamin, protein S100-A9 and immunoglobulin heavy constant gamma 3 (IGHG3) were validated. IGHG3 was elevated (p=0.037) while A1AG1 was reduced (p=0.003) in responders as compared to non-responders. Gene expression of IGHG3 and ORM1 in resistant cells showed consistent results with the proteomics profiles.

Conclusion: Serum expression levels of IGHG3 and A1AG1 proteins may be useful to recruit an NSCLC subpopulation that can benefit from CAR plus PTX standard therapy.

Keywords: Serum; carboplatin; non-small cell lung cancer; paclitaxel; proteomic.

MeSH terms

  • A549 Cells
  • Aged
  • Aged, 80 and over
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Biomarkers, Tumor / blood*
  • Carboplatin / therapeutic use
  • Carcinoma, Non-Small-Cell Lung / blood*
  • Carcinoma, Non-Small-Cell Lung / drug therapy
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Clinical Decision-Making
  • Drug Resistance, Neoplasm
  • Female
  • Humans
  • Lung Neoplasms / blood*
  • Lung Neoplasms / drug therapy
  • Lung Neoplasms / pathology
  • Male
  • Middle Aged
  • Orosomucoid / analysis*
  • Paclitaxel / therapeutic use
  • Predictive Value of Tests
  • Proteomics*
  • Treatment Outcome

Substances

  • Biomarkers, Tumor
  • ORM1 protein, human
  • Orosomucoid
  • Carboplatin
  • Paclitaxel