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Gregory J. Riely, MD, PhD


Bevacizumab for Advanced NSCLC: DNA Methylation Signature as a Predictive Biomarker?

By: Julia Fiederlein
Posted: Wednesday, September 7, 2022

Linlin Wang, MD, PhD, of Shandong First Medical University, China, and colleagues established a 10-gene DNA methylation signature to identify patients with advanced non–small cell lung cancer (NSCLC) who may derive a clinical benefit from treatment with the monoclonal anti-VEGF antibody bevacizumab. Their findings, which were published in BMC Cancer, may help to optimize treatment strategies in this setting.

“The pattern of DNA methylation alterations…[is] considered to be involved in lung cancer carcinogenesis and [the] development of drug resistance,” the investigators commented. “Promoter methylations, a common event in NSCLC, are fit for tracking the signals due to their early and persistent existence in cancer development.”

Using samples from 20 patients who were treated with bevacizumab plus chemotherapy, the investigators performed genome-wide DNA methylation profiling; this population was divided into better (n = 10) and inferior (n = 10) prognostic groups based on their survival, and comparative methylation and functional enrichment analyses were conducted. To establish the DNA methylation signature, a total of 1,464 genes related to survival were included in the least absolute shrinkage and selection operator regression analyses. The investigators further analyzed the immune cell abundance associated with the signature in patients with lung adenocarcinoma from the TISIDB database.

The DNA methylation profiles seemed to significantly differ between the prognostic groups. Related genes of differentially methylated regions were found to be significantly enriched in cell projection assembly, neutrophil-mediated immunity, the VEGFA/VEGFR2 signaling pathway, and neutrophil degranulation. The C-index of the signature was 0.76, which according to the investigators implies a high predictive accuracy. The abundance of ActCD4, Th1, ActCD8, NKT, and neutrophil cells was found to be related to the methylation of most of the host genes of the signature.

Disclosure: The study authors reported no conflicts of interest.

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