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SSO 2024: Is Image-Based Obesity Linked to Metabolic Pathway Alterations in NSCLC?

By: Julia Fiederlein Cipriano, MS
Posted: Monday, March 25, 2024

Image-based measures of adiposity appear to be associated with significant gene-expression changes in non–small cell lung cancer (NSCLC), according to Sai Yendamuri, MD, MBA, of Roswell Park Comprehensive Cancer Center, Buffalo, and colleagues. Their findings, which were presented during the 2024 Society of Surgical Oncology (SSO) Annual Meeting (Abstract 37), identified metabolic vulnerabilities that may be manipulated as new approaches to therapy.

“Using both preclinical models and outcome data, we have previously demonstrated the obesity paradox in NSCLC is an artifact induced by the use of body mass index as a measure of obesity,” the investigators commented. “However, the mechanistic basis of the relationship between adiposity and lung cancer behavior is yet to be unraveled.”

As an initial foray in their investigation, the researchers examined the association of image-based total fat with ORIEN project–generated tumor gene-expression data from 143 adenocarcinoma and squamous cell carcinomas. Employing a metabolic analysis pipeline, they used the identified gene-expression differences to map out alterations in metabolic pathways.

Of the 53,425 transcripts considered to be expressed, 1,154 demonstrated differential expression (P < .05). The 20 pathways most highly enriched with adiposity were identified, with an equal number showing upregulation and downregulation; according to the researchers, several of these involved metabolic pathways central to normal physiology and cancer growth. They found 58 metabolic pathways to be significantly enriched in patients with high vs low total fat area, some of which they expected (ie, lipids), and others they did not. Butanoate metabolism, linoleic acid metabolism, biosynthesis of unsaturated fatty acids, and folate one-carbon metabolism appeared to be among the most highly enriched.

Disclosure: For full disclosures of the other study authors, visit

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