Hao Li1,2, Kamala Vanarsa2, Ting Zhang2, Sanam Soomro2, Pietro Antonio Cicalese2, Valeria Duran2, Shobha Dasari2, Kyung Hyun Lee3, Claudia Pedroza3, John B Kisiel4, Huanlong Qin1, Robert S Bresalier5, Nicholas Chia6, Chandra Mohan7. 1. Department of General Surgery, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China. 2. Department of Biomedical Engineering, University of Houston, Houston, USA. 3. Center for Clinical Research and Evidence-Based Medicine, McGovern Medical School, UT Health Science Center At Houston, Houston, USA. 4. Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, USA. 5. Department of Gastroenterology, Hepatology and Nutrition, The University of Texas MD Anderson Cancer Center, Houston, USA. 6. Department of Surgical Research, Mayo Clinic, Rochester, USA. 7. Department of Biomedical Engineering, University of Houston, Houston, USA. cmohan@central.uh.edu.
Abstract
BACKGROUND: To screen and validate novel stool protein biomarkers of colorectal cancer (CRC). METHODS: A novel aptamer-based screen of 1317 proteins was used to uncover elevated proteins in the stool of patients with CRC, as compared to healthy controls (HCs) in a discovery cohort. Selected biomarker candidates from the discovery cohort were ELISA validated in three independent cross-sectional cohorts comprises 76 CRC patients, 15 adenoma patients, and 63 healthy controls, from two different ethnicities. The expression of the potential stool biomarkers within CRC tissue was evaluated using single-cell RNA-seq datasets. RESULTS: A total of 92 proteins were significantly elevated in CRC samples as compared to HCs in the discovery cohort. Among Caucasians, the 5 most discriminatory proteins among the 16 selected proteins, ordered by their ability to distinguish CRC from adenoma and healthy controls, were MMP9, haptoglobin, myeloperoxidase, fibrinogen, and adiponectin. Except myeloperoxidase, the others were significantly associated with depth of tumor invasion. The 8 stool proteins with the highest AUC values were also discriminatory in a second cohort of Indian CRC patients. Several of the stool biomarkers elevated in CRC were also expressed within CRC tissue, based on the single-cell RNA-seq analysis. CONCLUSIONS: Stool MMP9, fibrinogen, myeloperoxidase, and haptoglobin emerged as promising CRC stool biomarkers, outperforming stool Hemoglobin. Longitudinal studies are warranted to assess the clinical utility of these novel biomarkers in early diagnosis of CRC.
BACKGROUND: To screen and validate novel stool protein biomarkers of colorectal cancer (CRC). METHODS: A novel aptamer-based screen of 1317 proteins was used to uncover elevated proteins in the stool of patients with CRC, as compared to healthy controls (HCs) in a discovery cohort. Selected biomarker candidates from the discovery cohort were ELISA validated in three independent cross-sectional cohorts comprises 76 CRC patients, 15 adenoma patients, and 63 healthy controls, from two different ethnicities. The expression of the potential stool biomarkers within CRC tissue was evaluated using single-cell RNA-seq datasets. RESULTS: A total of 92 proteins were significantly elevated in CRC samples as compared to HCs in the discovery cohort. Among Caucasians, the 5 most discriminatory proteins among the 16 selected proteins, ordered by their ability to distinguish CRC from adenoma and healthy controls, were MMP9, haptoglobin, myeloperoxidase, fibrinogen, and adiponectin. Except myeloperoxidase, the others were significantly associated with depth of tumor invasion. The 8 stool proteins with the highest AUC values were also discriminatory in a second cohort of Indian CRC patients. Several of the stool biomarkers elevated in CRC were also expressed within CRC tissue, based on the single-cell RNA-seq analysis. CONCLUSIONS: Stool MMP9, fibrinogen, myeloperoxidase, and haptoglobin emerged as promising CRC stool biomarkers, outperforming stool Hemoglobin. Longitudinal studies are warranted to assess the clinical utility of these novel biomarkers in early diagnosis of CRC.
Authors: James Turvill; Samantha Mellen; Laura Jeffery; Sarah Bevan; Ada Keding; Daniel Turnock Journal: Scand J Gastroenterol Date: 2019-01-08 Impact factor: 2.423
Authors: Hisham K Dabbous; Yosry Abd El-Rahman Mohamed; Runia F El-Folly; Mohamed D El-Talkawy; Hani E Seddik; Dina Johar; Mohammed A Sarhan Journal: J Gastrointest Cancer Date: 2019-09
Authors: Ann G Zauber; Sidney J Winawer; Michael J O'Brien; Iris Lansdorp-Vogelaar; Marjolein van Ballegooijen; Benjamin F Hankey; Weiji Shi; John H Bond; Melvin Schapiro; Joel F Panish; Edward T Stewart; Jerome D Waye Journal: N Engl J Med Date: 2012-02-23 Impact factor: 91.245
Authors: Douglas A Corley; Christopher D Jensen; Amy R Marks; Wei K Zhao; Jeffrey K Lee; Chyke A Doubeni; Ann G Zauber; Jolanda de Boer; Bruce H Fireman; Joanne E Schottinger; Virginia P Quinn; Nirupa R Ghai; Theodore R Levin; Charles P Quesenberry Journal: N Engl J Med Date: 2014-04-03 Impact factor: 91.245
Authors: Linda J W Bosch; Meike de Wit; Thang V Pham; Veerle M H Coupé; Annemieke C Hiemstra; Sander R Piersma; Gideon Oudgenoeg; George L Scheffer; Sandra Mongera; Jochim Terhaar Sive Droste; Frank A Oort; Sietze T van Turenhout; Ilhame Ben Larbi; Joost Louwagie; Wim van Criekinge; Rene W M van der Hulst; Chris J J Mulder; Beatriz Carvalho; Remond J A Fijneman; Connie R Jimenez; Gerrit A Meijer Journal: Ann Intern Med Date: 2017-11-21 Impact factor: 25.391