Adipose tissue and skeletal muscle wasting precede clinical diagnosis of pancreatic cancer

Ana Babic; Michael H Rosenthal; Tilak K Sundaresan; Natalia Khalaf; Valerie Lee; Lauren K Brais; Maureen Loftus; Leah Caplan; Sarah Denning; Anamol Gurung; Joanna Harrod; Khoschy Schawkat; Chen Yuan; Qiao-Li Wang; Alice A Lee; Leah H Biller; Matthew B Yurgelun; Kimmie Ng; Jonathan A Nowak; Andrew J Aguirre; Sangeeta N Bhatia; Matthew G Vander Heiden; Stephen K Van Den Eeden; Bette J Caan; Brian M Wolpin

doi:10.1038/s41467-023-40024-3

Adipose tissue and skeletal muscle wasting precede clinical diagnosis of pancreatic cancer

Nat Commun. 2023 Jul 18;14(1):4317. doi: 10.1038/s41467-023-40024-3.

Authors

Ana Babic^#¹, Michael H Rosenthal^#², Tilak K Sundaresan^#³, Natalia Khalaf⁴, Valerie Lee⁵, Lauren K Brais¹, Maureen Loftus¹, Leah Caplan¹, Sarah Denning¹, Anamol Gurung¹, Joanna Harrod¹, Khoschy Schawkat², Chen Yuan¹, Qiao-Li Wang^{1

6}, Alice A Lee⁷, Leah H Biller^{1

8}, Matthew B Yurgelun^{1

8}, Kimmie Ng^{1

8}, Jonathan A Nowak⁹, Andrew J Aguirre^{1

8}, Sangeeta N Bhatia^{8

10

11

12

13

14

15}, Matthew G Vander Heiden^{1

11

13

16}, Stephen K Van Den Eeden⁵, Bette J Caan⁵, Brian M Wolpin^{17

18}

Affiliations

¹ Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
² Department of Radiology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
³ Kaiser Permanente San Francisco, San Francisco, CA, USA.
⁴ Center for Innovations in Quality, Effectiveness, and Safety (IQuESt), Michael E. DeBakey Veterans Affairs Medical Center; Section of Gastroenterology and Hepatology, Department of Medicine, Baylor College of Medicine, Houston, TX, USA.
⁵ Division of Research, Kaiser Permanente Northern California, Oakland, CA, USA.
⁶ Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden.
⁷ Division of Gastroenterology, Hepatology and Endoscopy, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
⁸ Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
⁹ Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
¹⁰ Harvard-MIT Division of Health Sciences and Technology, Institute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, MA, USA.
¹¹ Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA.
¹² Department of Electrical Engineering and Computer Science, Massachusetts Institute of Technology, Cambridge, MA, USA.
¹³ Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, MA, USA.
¹⁴ Wyss Institute, Harvard University, Boston, MA, USA.
¹⁵ Howard Hughes Medical Institute, Cambridge, MA, USA.
¹⁶ Department of Biology, Massachusetts Institute of Technology, Cambridge, MA, USA.
¹⁷ Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA. brian_wolpin@dfci.harvard.edu.
¹⁸ Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA. brian_wolpin@dfci.harvard.edu.

^# Contributed equally.

Abstract

Patients with pancreatic cancer commonly develop weight loss and muscle wasting. Whether adipose tissue and skeletal muscle losses begin before diagnosis and the potential utility of such losses for earlier cancer detection are not well understood. We quantify skeletal muscle and adipose tissue areas from computed tomography (CT) imaging obtained 2 months to 5 years before cancer diagnosis in 714 pancreatic cancer cases and 1748 matched controls. Adipose tissue loss is identified up to 6 months, and skeletal muscle wasting is identified up to 18 months before the clinical diagnosis of pancreatic cancer and is not present in the matched control population. Tissue losses are of similar magnitude in cases diagnosed with localized compared with metastatic disease and are not correlated with at-diagnosis circulating levels of CA19-9. Skeletal muscle wasting occurs in the 1-2 years before pancreatic cancer diagnosis and may signal an upcoming diagnosis of pancreatic cancer.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Adipose Tissue / metabolism
Body Composition*
Cachexia / diagnosis
Cachexia / etiology
Cachexia / metabolism
Humans
Muscle, Skeletal / metabolism
Muscular Atrophy / pathology
Pancreatic Neoplasms* / complications
Pancreatic Neoplasms* / diagnosis
Pancreatic Neoplasms* / metabolism

Abstract

Publication types

MeSH terms

Grants and funding