TP53 and EGFR Amplification Are Negative Predictors of Overall Survival in Patients Diagnosed with Non-small Cell Lung Cancer with Brain Metastases

Overview

Journal Heliyon

Specialty Social Sciences

Date 2024 Sep 11

PMID 39258211

Authors

Tao Lin

Xusheng Tang

Wanli Yang

Hainan Yang

Zhaoming Zhou

Zhijie Chen

Yongqin Zeng

Weiping Hong

Minting Ye

Linbo Cai

Da Liu

Minying Li

Lei Wen

Affiliations

Soon will be listed here.

Abstract

Background: The discovery of driver genes such as , , and has dramatically shifted treatment patterns in patients harboring these oncogenes. However, dissemination into the central nervous system (CNS) is a severe complication. In addition, the particular anatomical structure of the CNS has made it difficult to obtain tissue specimens from brain metastases (BM) to generate a gene map, as such, potential predictive markers for survival in patients with non-small cell lung cancer (NSCLC) and BM (NSCLC-BM) remain unclear.

Methods: Data from 28 patients diagnosed with NSCLC-BM between June 2019 and May 2021 at Guangdong Sanjiu Brain Hospital (Guangzhou, China), were reviewed. Targeted next-generation sequencing (NGS) of a 168 cancer-related gene panel was available for surgically resected brain tissues from all patients. In addition, molecular characteristics and overall survival (OS) were analyzed to determine potential predictive markers.

Results: Among patients with NSCLC-BM, NGS revealed that was the most frequent mutation (61 %), with a detection rate of 39 %, closely by amplification. Additionally, , , , and were frequently observed (18 %). The median OS was significantly shorter in the mutation group than in the wildtype group (14 versus undefined months, = 0.014). Similar results were also found in the genetic alteration of amplification, suggesting that amplification was associated with worse OS (14 vs. 24 months, = 0.039). Interestingly, NGS revealed that gene alternations such as , amplification, and , tended to coexist and such a co-alteration panel indicated worse clinical outcomes (median OS, 5 months). In addition, the detection rate of negative survival genes, including or amplification, was much higher in tumor tissues than in plasma samples, indicating the limited predictive value of matched PLA samples.

Conclusions: Gene signatures, such as or amplification, were associated with worse survival in patients diagnosed with NSCLC-BM. These valuable findings may shed light on new strategies for the prognostic assessment of specific patient groups.

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