AI Article Synopsis
- Chemoimmunotherapy is a common treatment for advanced non-small cell lung cancer (aNSCLC), but drug resistance limits its effectiveness, creating a need for reliable biomarkers to predict patient responses.
- Researchers conducted a three-phase study to identify and validate specific autoantibodies (AAbs) from 528 plasma samples of aNSCLC patients before and after treatment, using various microarray techniques and statistical analyses.
- They discovered two AAbs (MAX and DHX29) as pre-treatment biomarkers and two others (MAX and TAPBP) as predictive markers during treatment, with all showing significant correlations to patient outcomes like response rates and progression-free survival.
Article Abstract
Chemoimmunotherapy has evolved as a standard treatment for advanced non-small cell lung cancer (aNSCLC). However, inevitable drug resistance has limited its efficacy, highlighting the urgent need for biomarkers of chemoimmunotherapy. A three-phase strategy to discover, verify, and validate longitudinal predictive autoantibodies (AAbs) for aNSCLC before and after chemoimmunotherapy was employed. A total of 528 plasma samples from 267 aNSCLC patients before and after anti-PD1 immunotherapy were collected, plus 30 independent formalin-fixed paraffin-embedded samples. Candidate AAbs were firstly selected using a HuProt high-density microarray containing 21,000 proteins in the discovery phase, followed by validation using an aNSCLC-focused microarray. Longitudinal predictive AAbs were chosen for ELISA based on responders versus non-responders comparison and progression-free survival (PFS) survival analysis. Prognostic markers were also validated using immunohistochemistry and publicly available immunotherapy datasets. We identified and validated a panel of two AAbs (MAX and DHX29) as pre-treatment biomarkers and another panel of two AAbs (MAX and TAPBP) as on-treatment predictive markers in aNSCLC patients undergoing chemoimmunotherapy. All three AAbs exhibited a positive correlation with early responses and PFS (p < 0.05). The kinetics of MAX AAb showed an increasing trend in responders (p < 0.05) and a tendency to initially increase and then decrease in non-responders (p < 0.05). Importantly, MAX protein and mRNA levels effectively discriminated PFS (p < 0.05) in aNSCLC patients treated with immunotherapy. Our results present a longitudinal analysis of changes in prognostic AAbs in aNSCLC patients undergoing chemoimmunotherapy.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11070596 | PMC |
| http://dx.doi.org/10.1016/j.mcpro.2024.100749 | DOI Listing |
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