Research Reveals a New Prognostic Factor for Advanced Lung Adenocarcinoma

New research has revealed that perilipin 2 protein modulates aggressive cancer progression in advanced lung adenocarcinoma, the most common type of lung cancer, by regulating lipid droplet accumulation, which plays an important role in lipid metabolism by making cancer cells store more fat, acting as a fuel source. Findings from this new study in The American Journal of Pathology, published by Elsevier, suggest that perilipin 2 could serve as a prognostic factor to help predict the likely outcome (prognosis) of the disease and point to new potential lipid-based targets for treating lung adenocarcinoma.

This study addresses an urgent unmet need for new therapeutic approaches focusing on perilipin 2, part of a family of proteins found on the surface of lipid droplets (fat storage units within cells), which plays a key role in lipid metabolism. Lipid metabolism supports cancer progression and helps remodel the tumor microenvironment through lipid uptake, storage, and lipogenesis.

“We need to study the underlying mechanisms for the progression and metastasis of lung adenocarcinoma to better understand the pathologic nature of these cancers and to discover new therapeutic targets,” explains lead investigator Kana Miyata-Morita, PhD, Department of Clinical Laboratory Science, Faculty of Medical Technology, Teikyo University, Tokyo, Japan.

Researchers analyzed 214 histologic samples that were selected from patients with lung adenocarcinoma who underwent surgical resection between 2010 and 2016 at the Teikyo University Hospital. Of those, 65 were perilipin 2 positive and 149 were perilipin 2 negative.

This study demonstrates that high perilipin 2 expression in lung adenocarcinoma was associated with more aggressive disease progression and shorter recurrence-free survival times than low perilipin 2 expression. Lung adenocarcinoma cell line with knockout of PLIN2 expression exhibited significant reduction in lipid droplet accumulation and suppression of cell proliferation and migration ability.

“Perilipin 2 is required for the maintenance of lipid droplets, which serve as an energy source driving cancer progression. These findings advance our understanding of lipid mechanisms in disease progression and will help estimate the likelihood of recurrence as well as help identify new targets to treat lung adenocarcinoma,” concludes Dr. Miyata-Morita.

Lung cancer is one of the most common cancers with high global morbidity and mortality rates. While targeted therapies for driver mutations (specific genetic changes) have improved outcomes for some advanced lung adenocarcinoma patients, many others lack these mutations and are typically unresponsive to currently available targeted therapies.

Notes for editors

The article is “Perilipin 2 Mediates Progression of Lung Adenocarcinoma by Modulating Lipid Metabolism,” by Kana Miyata-Morita, Akira Kawashima, Mitsuo Kiriya, Hitoshi Dejima, Koji Saito, Yukinori Sakao, Koichi Suzuki, Yuko Sasajima, and Shigeki Morita (https://doi.org/10.1016/j.ajpath.2025.05.016). It appears online in The American Journal of Pathology, ahead of volume 195, issue 9 (September 2025), published by Elsevier.

The article is openly available at https://ajp.amjpathol.org/article/S0002-9440(25)00202-0/fulltext.

Full text of the article is also available to credentialed journalists upon request. Contact Eileen Leahy at +1 732 406 1313 or [email protected] to request a PDF of the article or more information. To reach the study’s authors, contact Kana Miyata-Morita, PhD, at [email protected].

About The American Journal of Pathology

The American Journal of Pathology, official journal of the American Society for Investigative Pathology, published by Elsevier, seeks high-quality original research reports, reviews, and commentaries related to the molecular and cellular basis of disease. The editors will consider basic, translational, and clinical investigations that directly address mechanisms of pathogenesis or provide a foundation for future mechanistic inquiries. Examples of such foundational investigations include data mining, identification of biomarkers, molecular pathology, and discovery research. High priority is given to studies of human disease and relevant experimental models using molecular, cellular, and organismal approaches. ajp.amjpathol.org

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