Program Official

Principal Investigator

Awardee Organization

Beckman Research Institute/City Of Hope
United States

Fiscal Year
Activity Code
Early Stage Investigator Grants (ESI)
Not Applicable
Project End Date

Exosomal Biomarkers for the Noninvasive Detection of Colorectal Cancer

Colorectal cancer (CRC) is the second leading cause of cancer-related deaths in the United States. Yet, unlike other cancers, the majority of early stage CRCs are surgically curable. Therefore, early detection of CRCs and removal of precursor lesions, particularly advanced colorectal adenomas (A-CRA), is considered as the best approach in reducing CRC-associated mortality. However, current available screening procedures are impractical. In spite of the efficacy of colonoscopy as a screening tool, its invasive nature and expense often dissuade individuals to follow CRC screening guidelines; and inaccuracy of fecal-based tests remains insufficient as a diagnostic modality. Accumulating evidence indicates that dysregulation of microRNAs (miRNAs) occurs in all human cancers. As biomarkers, miRNAs are more resilient than mRNAs as they are less prone to degradation, and are frequently deregulated even in the earliest stages of neoplasia compared to genetic alterations. Furthermore, the recent discovery that cancers actively excrete small extracellular vesicles, called “exosomes”, into systemic circulation, has brought additional enthusiasm to the field of translational biomarker research. Even though exosomes are considered promising due to their structural stability and molecular profiles reflecting their cell-of-origin, utilization of exosomes in biomarker research has been hampered due to multiple reasons, including: i) lack of standardized protocols for their isolation and purification; ii) use of cell line-derived, not patient-derived specimens for biomarker discovery; iii) lack of molecular profiling studies on cancer-derived exosomes from matched tissues and plasma specimens to establish their cancer specificity; iv) albeit the perception that exosomal-miRNAs (exo-miRNAs) may be superior to circulating cell-free miRNAs (cf-miRNAs), no studies have undertaken an effort to directly compare these two types, in order to support or negate the superiority of either type, as clinically-relevant disease biomarkers. In this proposal, we will address these concerns by undertaking the following Specific Aims. Aim 1: Optimization of patient-derived exosome isolation, followed by RNA-Seq based discovery of circulating cell-free (cf-miRNAs) and exosomal miRNAs (exomiRNAs) in matched tissue and plasma specimens collected from patients with A-CRAs, CRCs and individuals with normal colon. Aim 2: Development of circulating cell-free and exosomal miRNA biomarker panels that distinguish patients with A-CRAs and CRCs from healthy individuals. Aim 3: Clinical validation and performance evaluation of optimized cf-miRNAs and exo-miRNAs in large, independent patient cohorts with colorectal neoplasia. If successful, this proposal will provide much needed molecular characterization of cell-free and exosomal miRNA biomarkers as liquid biopsy biomarkers, which may transform early-detection of CRC into a robust, noninvasive, and inexpensive clinical assay.


  • Okuno K, Tokunaga M, Von Hoff D, Kinugasa Y, Goel A, PDAC Biomarker Working Group, Takahashi N, Yamada Y, Kanda M, Kodera Y, Baba H. Intratumoral Malasseziaglobosa Levels Predict Survival and Therapeutic Response to Adjuvant Chemotherapy in Patients With Pancreatic Ductal Adenocarcinoma. Gastroenterology. 2023 Aug;165(2):502-504.e2. Epub 2023 Apr 28. PMID: 37119937
  • Wada Y, Shimada M, Morine Y, Ikemoto T, Saito Y, Baba H, Mori M, Goel A. A blood-based noninvasive miRNA signature for predicting survival outcomes in patients with intrahepatic cholangiocarcinoma. British journal of cancer. 2022 May;126(8):1196-1204. Epub 2022 Jan 25. PMID: 35079106
  • Roy S, Zhao Y, Yuan YC, Goel A. Metformin and ICG-001 Act Synergistically to Abrogate Cancer Stem Cells-Mediated Chemoresistance in Colorectal Cancer by Promoting Apoptosis and Autophagy. Cancers. 2022 Mar 2;14. (5). PMID: 35267590
  • Ruiz-Bañobre J, Goel A. Genomic and epigenomic biomarkers in colorectal cancer: From diagnosis to therapy. Advances in cancer research. 2021;151:231-304. Epub 2021 Mar 29. PMID: 34148615
  • Jansen AML, Goel A. Mosaicism in Patients With Colorectal Cancer or Polyposis Syndromes: A Systematic Review. Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association. 2020 Aug;18(9):1949-1960. Epub 2020 Mar 5. PMID: 32147591
  • Shimura T, Kandimalla R, Okugawa Y, Ohi M, Toiyama Y, He C, Goel A. Novel evidence for m6A methylation regulators as prognostic biomarkers and FTO as a potential therapeutic target in gastric cancer. British journal of cancer. 2022 Feb;126(2):228-237. Epub 2021 Oct 21. PMID: 34675398
  • Xu C, Jun E, Okugawa Y, Toiyama Y, Borazanci E, Bolton J, Taketomi A, Kim SC, Shang D, Von Hoff D, Zhang G, Goel A. A Circulating Panel of circRNA Biomarkers for the Noninvasive and Early Detection of Pancreatic Ductal Adenocarcinoma. Gastroenterology. 2024 Jan;166(1):178-190.e16. Epub 2023 Oct 14. PMID: 37839499
  • Zhao Y, Peng F, Wang C, Murano T, Baba H, Ikematsu H, Li W, Goel A. A DNA Methylation-based Epigenetic Signature for the Identification of Lymph Node Metastasis in T1 Colorectal Cancer. Annals of surgery. 2023 Apr 1;277(4):655-663. Epub 2022 Jul 15. PMID: 35837968
  • Sharma GG, Okada Y, Von Hoff D, Goel A. Non-coding RNA biomarkers in pancreatic ductal adenocarcinoma. Seminars in cancer biology. 2021 Oct;75:153-168. Epub 2020 Oct 10. PMID: 33049362
  • Okuno K, Tokunaga M, Kinugasa Y, Baba H, Kodera Y, Goel A. A Transcriptomic Liquid Biopsy Assay for Predicting Resistance to Neoadjuvant Therapy in Esophageal Squamous Cell Carcinoma. Annals of surgery. 2022 Jul 1;276(1):101-110. Epub 2022 May 12. PMID: 35703443
  • Matsuyama T, Kandimalla R, Ishikawa T, Takahashi N, Yamada Y, Yasuno M, Kinugasa Y, Hansen TF, Fakih M, Uetake H, Győrffy B, Goel A. A novel mesenchymal-associated transcriptomic signature for risk-stratification and therapeutic response prediction in colorectal cancer. International journal of cancer. 2020 Dec 1;147(11):3250-3261. Epub 2020 Jul 13. PMID: 32657428
  • Wada Y, Shimada M, Morine Y, Ikemoto T, Saito Y, Baba H, Mori M, Goel A. A transcriptomic signature that predicts cancer recurrence after hepatectomy in patients with colorectal liver metastases. European journal of cancer (Oxford, England : 1990). 2022 Mar;163:66-76. Epub 2022 Jan 14. PMID: 35042069
  • Kandimalla R, Shimura T, Mallik S, Sonohara F, Tsai S, Evans DB, Kim SC, Baba H, Kodera Y, Von Hoff D, Chen X, Goel A. Identification of Serum miRNA Signature and Establishment of a Nomogram for Risk Stratification in Patients With Pancreatic Ductal Adenocarcinoma. Annals of surgery. 2022 Jan 1;275(1):e229-e237. PMID: 32398486
  • Lorzadeh A, Romero-Wolf M, Goel A, Jadhav U. Epigenetic Regulation of Intestinal Stem Cells and Disease: A Balancing Act of DNA and Histone Methylation. Gastroenterology. 2021 Jun;160(7):2267-2282. Epub 2021 Mar 26. PMID: 33775639
  • Zaidi AH, Pratama MY, Omstead AN, Gorbonova A, Mansoor R, Melton-Kreft R, Jobe BA, Wagner PL, Kelly RJ, Goel A. A blood-based circulating microbial metagenomic panel for early diagnosis and prognosis of oesophageal adenocarcinoma. British journal of cancer. 2022 Nov;127(11):2016-2024. Epub 2022 Sep 12. PMID: 36097175
  • Roy R, Kandimalla R, Sonohara F, Koike M, Kodera Y, Takahashi N, Yamada Y, Goel A. A comprehensive methylation signature identifies lymph node metastasis in esophageal squamous cell carcinoma. International journal of cancer. 2019 Mar 1;144(5):1160-1169. Epub 2018 Oct 16. PMID: 30006931
  • Nakamura K, Hernández G, Sharma GG, Wada Y, Banwait JK, González N, Perea J, Balaguer F, Takamaru H, Saito Y, Toiyama Y, Kodera Y, Boland CR, Bujanda L, Quintero E, Goel A. A Liquid Biopsy Signature for the Detection of Patients With Early-Onset Colorectal Cancer. Gastroenterology. 2022 Nov;163(5):1242-1251.e2. Epub 2022 Jul 16. PMID: 35850198
  • Wada Y, Shimada M, Murano T, Takamaru H, Morine Y, Ikemoto T, Saito Y, Balaguer F, Bujanda L, Pellise M, Kato K, Saito Y, Ikematsu H, Goel A. A Liquid Biopsy Assay for Noninvasive Identification of Lymph Node Metastases in T1 Colorectal Cancer. Gastroenterology. 2021 Jul;161(1):151-162.e1. Epub 2021 Apr 2. PMID: 33819484
  • Moloudizargari M, Asghari MH, Goel A. The therapeutic triad of extracellular vesicles: As drug targets, as drugs, and as drug carriers. Biochemical pharmacology. 2021 Oct;192:114714. Epub 2021 Jul 30. PMID: 34332957
  • Nguyen LH, Goel A, Chung DC. Pathways of Colorectal Carcinogenesis. Gastroenterology. 2020 Jan;158(2):291-302. Epub 2019 Oct 14. PMID: 31622622
  • Roy S, Kanda M, Nomura S, Zhu Z, Toiyama Y, Taketomi A, Goldenring J, Baba H, Kodera Y, Goel A. Diagnostic efficacy of circular RNAs as noninvasive, liquid biopsy biomarkers for early detection of gastric cancer. Molecular cancer. 2022 Feb 9;21(1):42. PMID: 35139874
  • Okada Y, Peng F, Perea J, Corchete L, Bujanda L, Li W, Goel A. Genome-wide methylation profiling identifies a novel gene signature for patients with synchronous colorectal cancer. British journal of cancer. 2023 Jan;128(1):112-120. Epub 2022 Nov 1. PMID: 36319845
  • Sahu D, Lin CC, Goel A. Transcriptomic Profiling Reveals an Enhancer RNA Signature for Recurrence Prediction in Colorectal Cancer. Genes. 2023 Jan 3;14. (1). PMID: 36672877
  • Antelo M, Golubicki M, Roca E, Mendez G, Carballido M, Iseas S, Cuatrecasas M, Moreira L, Sanchez A, Carballal S, Castells A, Boland CR, Goel A, Balaguer F. Lynch-like syndrome is as frequent as Lynch syndrome in early-onset nonfamilial nonpolyposis colorectal cancer. International journal of cancer. 2019 Aug 1;145(3):705-713. Epub 2019 Feb 23. PMID: 30693488
  • Miyazaki K, Xu C, Shimada M, Goel A. Curcumin and Andrographis Exhibit Anti-Tumor Effects in Colorectal Cancer via Activation of Ferroptosis and Dual Suppression of Glutathione Peroxidase-4 and Ferroptosis Suppressor Protein-1. Pharmaceuticals (Basel, Switzerland). 2023 Mar 2;16. (3). PMID: 36986483
  • Okuno K, Xu C, Pascual-Sabater S, Tokunaga M, Takayama T, Han H, Fillat C, Kinugasa Y, Goel A. Andrographis Reverses Gemcitabine Resistance through Regulation of ERBB3 and Calcium Signaling Pathway in Pancreatic Ductal Adenocarcinoma. Biomedicines. 2023 Jan 3;11. (1). PMID: 36672630
  • Jabandziev P, Kakisaka T, Bohosova J, Pinkasova T, Kunovsky L, Slaby O, Goel A. MicroRNAs in Colon Tissue of Pediatric Ulcerative Pancolitis Patients Allow Detection and Prognostic Stratification. Journal of clinical medicine. 2021 Mar 23;10. (6). PMID: 33806966
  • Okuno K, Pratama MY, Li J, Tokunaga M, Wang X, Kinugasa Y, Goel A. Ginseng mediates its anticancer activity by inhibiting the expression of DNMTs and reactivating methylation-silenced genes in colorectal cancer. Carcinogenesis. 2023 Aug 10;44(5):394-403. PMID: 37137336
  • Kandimalla R, Wang W, Yu F, Zhou N, Gao F, Spillman M, Moukova L, Slaby O, Salhia B, Zhou S, Wang X, Goel A. OCaMIR-A Noninvasive, Diagnostic Signature for Early-Stage Ovarian Cancer: A Multi-cohort Retrospective and Prospective Study. Clinical cancer research : an official journal of the American Association for Cancer Research. 2021 Aug 1;27(15):4277-4286. Epub 2021 May 25. PMID: 34035068
  • Okuno K, Xu C, Pascual-Sabater S, Tokunaga M, Han H, Fillat C, Kinugasa Y, Goel A. Berberine Overcomes Gemcitabine-Associated Chemoresistance through Regulation of Rap1/PI3K-Akt Signaling in Pancreatic Ductal Adenocarcinoma. Pharmaceuticals (Basel, Switzerland). 2022 Sep 28;15. (10). PMID: 36297310