Deviation from the precisely timed age-associated patterns revealed by blood metabolomics to find CRC patients at risk of relapse at the CRC diagnosis.

Authors

null

Sheeno P. Thyparambil

mProbe Inc., Rockville, MD

Sheeno P. Thyparambil , Xiurui Zhu , Yani Zhang , Hui Sun , Junjie Peng , Sanjun Cai , Yaqi Li , Chen Fu , Pingping Bao , Shiying Hao , Zhen Li , Yun Ding , Xiaoming Yao , Wei-Li Liao , Robert Heaton , Zhi Han , Lu Tian , James Schilling , Karl G. Sylvester , Xuefeng Ling

Organizations

mProbe Inc., Rockville, MD, Shanghai Pulmonary Hospital/Tongji University School of Medicine, Shanghai, China, Fudan University Shanghai Cancer Center, Shanghai, China, Department of Colorectal Surgery, Fudan University Shanghai Cancer Center, Shanghai, China, Shanghai Municipal Center for Disease Control & Prevention, Shanghai, China, Stanford University Medical Center, Stanford University, Stanford, CA, mProbe Inc, Rockville, MD, Department of Health and Research Policy, Stanford University School of Medicine, Stanford, CA, Stanford University Medical Center, Stanford University, Palo Alto, CA

Research Funding

No funding received

Background: Human serum metabolome profiles have been analyzed to explore the molecular changes that occur with aging. We hypothesized that deep metabolic profiling of sera with different ages would allow the identification of distinct metabolic chronologic patterns as a normal biological baseline to study personal aging. We further hypothesized that metabolic assessment of this chronologic deviation, resulting from advanced precancerous lesion (APL) and stage I/II/III CRC, from the normal reference baseline, would be instrumental for prognosis of relapse revealing underlying pathophysiology. Methods: A cohort of normal (n=3,616, training; n=1,170, testing), 631 advanced adenoma, 1,019 stage I, 404 stage II and 417 stage III serum samples were assembled. Innovative global LCMS metabolomic production were applied to deep profile these subjects. Identification of the age-associated molecular patterns in normal subjects, modeled with an elastic net algorithm, established the reference baseline to mirror a metabolic clock. CRC associated deviation from the precise chronologically paced metabolic patterns was quantified to associate the clinical endpoints of relapse, OSF and PFS, and to identify the tightly associated metabolic pathways. Results: We observed that for those CRCs, the predicted metabolic age can differ from the chronological age with consistent variations, resulting “older” or “younger” metabolic age subgroup in reference to the chronological age. Significant disruptions from the normal baseline were observed in CRCs patients, and consistent stage specific patterns were observed. Outlier, “Older” or “younger” metabolic age subgroup, CRC patients were found with significant future relapse enrichment. Predictive models were derived to case find the patients at risk of future relapse at the CRC diagnosis timepoint. Conclusions: Deviations from the meticulously timed metabolic aging patterns may provide utility to allow prognosis of future clinical endpoints of relapse and overall survival. Close examination of the underlying metabolic pathways, associated with CRC stage specific metabolic patterns, disrupting the baseline ageotypes, not only may improve the sensitivity and specificity of prognostic tests of CRC relapse, but also shed new insights into CRC therapeutics.

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Abstract Details

Meeting

2022 ASCO Gastrointestinal Cancers Symposium

Session Type

Poster Session

Session Title

Poster Session C: Cancers of the Colon, Rectum, and Anus

Track

Colorectal Cancer,Anal Cancer

Sub Track

Other

DOI

10.1200/JCO.2022.40.4_suppl.206

Abstract #

206

Poster Bd #

K8

Abstract Disclosures

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