. 2023 Sep 19;4(9):101194.

doi: 10.1016/j.xcrm.2023.101194.

A blood-based metabolomic signature predictive of risk for pancreatic cancer

Ehsan Irajizad¹, Ana Kenney², Tiffany Tang², Jody Vykoukal³, Ranran Wu³, Eunice Murage³, Jennifer B Dennison³, Marta Sans⁴, James P Long⁵, Maureen Loftus⁶, John A Chabot⁷, Michael D Kluger⁷, Fay Kastrinos⁸, Lauren Brais⁶, Ana Babic⁶, Kunal Jajoo⁴, Linda S Lee⁴, Thomas E Clancy⁹, Kimmie Ng⁶, Andrea Bullock¹⁰, Jeanine M Genkinger¹¹, Anirban Maitra¹², Kim-Anh Do⁵, Bin Yu², Brian M Wolpin⁶, Sam Hanash¹³, Johannes F Fahrmann¹⁴

Affiliations

¹ Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA; Department of Clinical Cancer Prevention, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
² Department of Statistics, University of California, Berkeley, Berkeley, CA, USA.
³ Department of Clinical Cancer Prevention, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
⁴ Division of Gastroenterology, Hepatology and Endoscopy, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
⁵ Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
⁶ Dana-Farber Brigham and Women's Cancer Center, Division of Gastrointestinal Oncology, Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
⁷ Division of Digestive and Liver Diseases, Columbia University Irving Medical Cancer and the Vagelos College of Physicians and Surgeons, New York, NY, USA.
⁸ Division of Digestive and Liver Diseases, Columbia University Irving Medical Cancer and the Vagelos College of Physicians and Surgeons, New York, NY, USA; Herbert Irving Comprehensive Cancer Center, Columbia University Irving Medical Center, New York, NY, USA.
⁹ Dana-Farber Brigham and Women's Cancer Center, Division of Surgical Oncology, Department of Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA USA.
¹⁰ Division of Hematology/Oncology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
¹¹ Herbert Irving Comprehensive Cancer Center, Columbia University Irving Medical Center, New York, NY, USA; Department of Epidemiology, Columbia Mailman School of Public Health, New York, NY, USA.
¹² Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
¹³ Department of Clinical Cancer Prevention, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. Electronic address: shanash@mdanderson.org.
¹⁴ Department of Clinical Cancer Prevention, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. Electronic address: jffahrmann@mdanderson.org.

PMID: 37729870
PMCID: PMC10518621
DOI: 10.1016/j.xcrm.2023.101194

A blood-based metabolomic signature predictive of risk for pancreatic cancer

Ehsan Irajizad et al. Cell Rep Med. 2023.

. 2023 Sep 19;4(9):101194.

doi: 10.1016/j.xcrm.2023.101194.

Authors

Affiliations

¹ Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA; Department of Clinical Cancer Prevention, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
² Department of Statistics, University of California, Berkeley, Berkeley, CA, USA.
³ Department of Clinical Cancer Prevention, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
⁴ Division of Gastroenterology, Hepatology and Endoscopy, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
⁵ Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
⁶ Dana-Farber Brigham and Women's Cancer Center, Division of Gastrointestinal Oncology, Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
⁷ Division of Digestive and Liver Diseases, Columbia University Irving Medical Cancer and the Vagelos College of Physicians and Surgeons, New York, NY, USA.
⁸ Division of Digestive and Liver Diseases, Columbia University Irving Medical Cancer and the Vagelos College of Physicians and Surgeons, New York, NY, USA; Herbert Irving Comprehensive Cancer Center, Columbia University Irving Medical Center, New York, NY, USA.
⁹ Dana-Farber Brigham and Women's Cancer Center, Division of Surgical Oncology, Department of Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA USA.
¹⁰ Division of Hematology/Oncology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
¹¹ Herbert Irving Comprehensive Cancer Center, Columbia University Irving Medical Center, New York, NY, USA; Department of Epidemiology, Columbia Mailman School of Public Health, New York, NY, USA.
¹² Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
¹³ Department of Clinical Cancer Prevention, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. Electronic address: shanash@mdanderson.org.
¹⁴ Department of Clinical Cancer Prevention, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. Electronic address: jffahrmann@mdanderson.org.

PMID: 37729870
PMCID: PMC10518621
DOI: 10.1016/j.xcrm.2023.101194

Abstract

Emerging evidence implicates microbiome involvement in the development of pancreatic cancer (PaCa). Here, we investigate whether increases in circulating microbial-related metabolites associate with PaCa risk by applying metabolomics profiling to 172 sera collected within 5 years prior to PaCa diagnosis and 863 matched non-subject sera from participants in the Prostate, Lung, Colorectal, and Ovarian (PLCO) cohort. We develop a three-marker microbial-related metabolite panel to assess 5-year risk of PaCa. The addition of five non-microbial metabolites further improves 5-year risk prediction of PaCa. The combined metabolite panel complements CA19-9, and individuals with a combined metabolite panel + CA19-9 score in the top 2.5th percentile have absolute 5-year risk estimates of >13%. The risk prediction model based on circulating microbial and non-microbial metabolites provides a potential tool to identify individuals at high risk of PaCa that would benefit from surveillance and/or from potential cancer interception strategies.

Keywords: biomarker; metabolites; microbiome; pancreatic cancer; risk assessment.

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Conflict of interest statement

Declaration of interests An invention disclosure report related to findings reported herein has been submitted to the University of Texas. B.M.W. receives research funding from Celgene and Eli Lilly and does consulting for BioLineRx, Celgene, and GRAIL.

Figures

**Figure 1**
Relationship between TMAO and indoleacrylic acid and microbial species (A) Association between TMAO and indoleacrlyic acid with different microbial species. Data were derived from the Metabolomics Data Explorer database (see STAR methods). Data were derived from N = 2–8 biological replicates. (B) Association between referenced microbial species and pancreatic cancer.

**Figure 2**
Area under the reciever operating characteristic curves for 5-year risk prediction of pancreatic cancer in the PLCO cohort Predictive performance estimates for the metabolite (microbial + non-microbial) panel, CA19-9, and the metabolite panel + CA19-9 for 5-year risk prediction of pancreatic cancer in the PLCO set-aside test set (A) and the entire PLCO specimen set (B).

**Figure 3**
Absolute 5-year risk estimates for individuals with CA19-9 + 3-marker microbial panel + 5-marker non-microbial panel scores Vertical lines represent 20th, 40th, 60th, and 80th percentile values. Table on the bottom provides absolute 5-year risk estimates for individuals with CA19-9, combined metabolite panel (3-marker microbial metabolite panel + 5-marker non-microbial metabolite panel), and the combined metabolite panel + CA19-9 scores.

See this image and copyright information in PMC

Comment in

Where the metabolome meets the microbiome for pancreatic cancer detection.
Oldfield L, Costello E. Oldfield L, et al. Cell Rep Med. 2023 Sep 19;4(9):101011. doi: 10.1016/j.xcrm.2023.101011. Cell Rep Med. 2023. PMID: 37729875 Free PMC article.
A Blood-based Metabolite Signature for Personalized Risk Assessment of Pancreatic Cancer.
León-Letelier RA, Chen Y, Ballaro R, Irajizad E, Do KA, Maitra A, Zhang J, Schmidt CM, Fahrmann JF. León-Letelier RA, et al. J Cancer Immunol (Wilmington). 2024;6(4):148-153. doi: 10.33696/cancerimmunol.6.095. J Cancer Immunol (Wilmington). 2024. PMID: 39713022 Free PMC article. No abstract available.

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A blood-based metabolomic signature predictive of risk for pancreatic cancer

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A blood-based metabolomic signature predictive of risk for pancreatic cancer

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