AUTHOR=Luu Jennifer K. , Johnson Fraser D. , Jajarmi Jana , Sihota Tianna , Shi Rocky , Lu Daniel , Farnsworth Dylan , Spencer Sandra E. , Negri Gian Luca , Morin Gregg B. , Lockwood William W. TITLE=Characterizing the secretome of EGFR mutant lung adenocarcinoma JOURNAL=Frontiers in Oncology VOLUME=13 YEAR=2024 URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2023.1286821 DOI=10.3389/fonc.2023.1286821 ISSN=2234-943X ABSTRACT=Background

Lung cancer is the leading cause of cancer related death worldwide, mainly due to the late stage of disease at the time of diagnosis. Non-invasive biomarkers are needed to supplement existing screening methods to enable earlier detection and increased patient survival. This is critical to EGFR-driven lung adenocarcinoma as it commonly occurs in individuals who have never smoked and do not qualify for current screening protocols.

Methods

In this study, we performed mass spectrometry analysis of the secretome of cultured lung cells representing different stages of mutant EGFR driven transformation, from normal to fully malignant. Identified secreted proteins specific to the malignant state were validated using orthogonal methods and their clinical activity assessed in lung adenocarcinoma patient cohorts.

Results

We quantified 1020 secreted proteins, which were compared for differential expression between stages of transformation. We validated differentially expressed proteins at the transcriptional level in clinical tumor specimens, association with patient survival, and absolute concentration to yield three biomarker candidates: MDK, GDF15, and SPINT2. These candidates were validated using ELISA and increased levels were associated with poor patient survival specifically in EGFR mutant lung adenocarcinoma patients.

Conclusions

Our study provides insight into changes in secreted proteins during EGFR driven lung adenocarcinoma transformation that may play a role in the processes that promote tumor progression. The specific candidates identified can harnessed for biomarker use to identify high risk individuals for early detection screening programs and disease management for this molecular subgroup of lung adenocarcinoma patients.