Global metabolomics revealed deviations from the metabolic aging clock in colorectal cancer patients

Zhang, Long; Mo, Shaobo; Zhu, Xiurui; Chou, C. James; Jin, Bo; Han, Zhi; Schilling, James; Liao, Weili; Thyparambil, Sheeno; Luo, Ruben Y.; Whitin, John C.; Tian, Lu; Nagpal, Seema; Ceresnak, Scott R.; Cohen, Harvey J.; McElhinney, Doff B.; Sylvester, Karl G.; Gong, Yangming; Fu, Chen; Ling, Xuefeng B.; Peng, Junjie

doi:10.7150/thno.87303

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Nanotheranostics 2024; 8(4): 442-457. [Abstract] [Full text] [PDF]

Nanotheranostics 2024; 8(4): 427-441. [Abstract] [Full text] [PDF]

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Theranostics 2024; 14(4):1602-1614. doi:10.7150/thno.87303 This issue Cite

Research Paper

Global metabolomics revealed deviations from the metabolic aging clock in colorectal cancer patients

Long Zhang^1,2,3,*, Shaobo Mo^1,2,*, Xiurui Zhu^4,*, C. James Chou^5,*, Bo Jin⁴, Zhi Han⁵, James Schilling^6,7,8, Weili Liao⁴, Sheeno Thyparambil⁴, Ruben Y. Luo⁵, John C. Whitin⁵, Lu Tian⁵, Seema Nagpal⁵, Scott R. Ceresnak⁵, Harvey J. Cohen⁵, Doff B. McElhinney⁵, Karl G. Sylvester⁵, Yangming Gong⁹, Chen Fu^9,10,✉, Xuefeng B. Ling^5,✉, Junjie Peng^1,2,✉

1. Department of Colorectal Surgery, Fudan University Shanghai Cancer Center; Shanghai, China.
2. Department of Oncology, Shanghai Medical College, Fudan University; Shanghai, China.
3. Cancer Research Institute, Fudan University Shanghai Cancer Center; Shanghai, China.
4. mProbe Inc.; Rockville, MD, USA.
5. School of Medicine, Stanford University; Stanford, CA, USA.
6. Shanghai Yunxiang Medical Technology Co., Ltd.; Shanghai, China.
7. Tianjin Yunjian Medical Technology Co. Ltd.; Tianjin, China.
8. Binhai Industrial Technology Research Institute, Zhejiang University; Tianjin, China.
9. Shanghai Municipal Center for Disease Control and Prevention; Shanghai, China.
10. Shanghai Clinical Research Center for Aging and Medicine; Shanghai, China.
*These authors contributed equally to this work.

Citation:

Zhang L, Mo S, Zhu X, Chou CJ, Jin B, Han Z, Schilling J, Liao W, Thyparambil S, Luo RY, Whitin JC, Tian L, Nagpal S, Ceresnak SR, Cohen HJ, McElhinney DB, Sylvester KG, Gong Y, Fu C, Ling XB, Peng J. Global metabolomics revealed deviations from the metabolic aging clock in colorectal cancer patients. Theranostics 2024; 14(4):1602-1614. doi:10.7150/thno.87303. https://www.thno.org/v14p1602.htm

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Abstract

Background: Markers of aging hold promise in the context of colorectal cancer (CRC) care. Utilizing high-resolution metabolomic profiling, we can unveil distinctive age-related patterns that have the potential to predict early CRC development. Our study aims to unearth a panel of aging markers and delve into the metabolomic alterations associated with aging and CRC.

Methods: We assembled a serum cohort comprising 5,649 individuals, consisting of 3,002 healthy volunteers, 715 patients diagnosed with colorectal advanced precancerous lesions (APL), and 1,932 CRC patients, to perform a comprehensive metabolomic analysis.

Results: We successfully identified unique age-associated patterns across 42 metabolic pathways. Moreover, we established a metabolic aging clock, comprising 9 key metabolites, using an elastic net regularized regression model that accurately estimates chronological age. Notably, we observed significant chronological disparities among the healthy population, APL patients, and CRC patients. By combining the analysis of circulative carcinoembryonic antigen levels with the categorization of individuals into the "hypo" metabolic aging subgroup, our blood test demonstrates the ability to detect APL and CRC with positive predictive values of 68.4% (64.3%, 72.2%) and 21.4% (17.8%, 25.9%), respectively.

Conclusions: This innovative approach utilizing our metabolic aging clock holds significant promise for accurately assessing biological age and enhancing our capacity to detect APL and CRC.

Keywords: Aging, Global metabolomics, Metabolic aging clock, Colorectal advanced precancerous lesions, Colorectal cancer

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APA

Zhang, L., Mo, S., Zhu, X., Chou, C.J., Jin, B., Han, Z., Schilling, J., Liao, W., Thyparambil, S., Luo, R.Y., Whitin, J.C., Tian, L., Nagpal, S., Ceresnak, S.R., Cohen, H.J., McElhinney, D.B., Sylvester, K.G., Gong, Y., Fu, C., Ling, X.B., Peng, J. (2024). Global metabolomics revealed deviations from the metabolic aging clock in colorectal cancer patients. Theranostics, 14(4), 1602-1614. https://doi.org/10.7150/thno.87303.

ACS

Zhang, L.; Mo, S.; Zhu, X.; Chou, C.J.; Jin, B.; Han, Z.; Schilling, J.; Liao, W.; Thyparambil, S.; Luo, R.Y.; Whitin, J.C.; Tian, L.; Nagpal, S.; Ceresnak, S.R.; Cohen, H.J.; McElhinney, D.B.; Sylvester, K.G.; Gong, Y.; Fu, C.; Ling, X.B.; Peng, J. Global metabolomics revealed deviations from the metabolic aging clock in colorectal cancer patients. Theranostics 2024, 14 (4), 1602-1614. DOI: 10.7150/thno.87303.

NLM

CSE

Zhang L, Mo S, Zhu X, Chou CJ, Jin B, Han Z, Schilling J, Liao W, Thyparambil S, Luo RY, Whitin JC, Tian L, Nagpal S, Ceresnak SR, Cohen HJ, McElhinney DB, Sylvester KG, Gong Y, Fu C, Ling XB, Peng J. 2024. Global metabolomics revealed deviations from the metabolic aging clock in colorectal cancer patients. Theranostics. 14(4):1602-1614.

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