Abstract 483P
Background
A staggering 1.8 million deaths attributed to lung cancer remains the foremost cause of cancer-related mortality, surpassing other cancer types. The underlying developmental trajectory of lung adenocarcinoma (LUAD) involves a progressive sequence from atypical adenomatous hyperplasia (AAH) to adenocarcinoma in situ (AIS), then to minimally invasive adenocarcinoma (MIA), and finally to invasive adenocarcinoma (IA). LUAD undergoes multifaceted molecular alterations throughout this continuum that drive its invasive behavior.
Methods
We curated a dataset encompassing 5,479 samples from 5,129 patients through PubMed and Web of Science. The dataset included 181 AAH samples, 761 AIS samples, 958 MIA samples, and 3,423 IA samples. Employing analytical tools like OpenMeta-analyst, we performed statistical analyses on the data and utilized MapChart for data visualization.
Results
In our study, weighted analysis via OpenMeta-analyst unveiled a progressive escalation in EGFR mutations during LUAD progression stages (AAH/AIS (26.4%) - MIA (46.8%) - IA (57.0%)), notably with a prominent increase in TP53 mutations during the IA stage (28.9%). Conversely, BARF and KRAS mutation frequencies exhibited a declining trend. Our study indicated that EGFR-sensitive mutations, including EGFR-L858R and EGFR-19Del, demonstrated an incremental mutation prevalence in tandem with LUAD advancement stages. Interestingly, similar trends emerged from our sample analysis focused on the Chinese population.
Conclusions
Our study demonstrates that the progression stages of lung adenocarcinoma involve many molecular events. EGFR mutations, including sensitive EGFR mutations, continuously increase in mutation frequency as lung adenocarcinoma evolves. Furthermore, during the transition toward an invasive tumor, there is an elevated frequency of TP53 mutations. These findings suggest that the initial cells giving rise to lung adenocarcinoma might not originate solely from EGFR mutations. Instead, EGFR mutations function as accelerators only during the progression stages of lung adenocarcinoma.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.
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