Principal Investigator

Youping
Deng
Awardee Organization

University Of Hawaii At Manoa
United States

Fiscal Year
2023
Activity Code
R01
Early Stage Investigator Grants (ESI)
Not Applicable
Project End Date

Circulating lipid and miRNA markers for early detection of breast cancer among women with abnormal mammograms

Breast cancer is the most common cancer among women in the world. When breast cancer is found in early stages, it can be effectively treated or even cured, but treating a patient in later stages is very difficult. Thus, early detection of breast cancer is critical. Mammography is the current gold standard for breast cancer screening; however, most women with abnormal mammograms are eventually found not to have breast cancer. Fewer than 5 per 1,000 women actually have the disease when they are screened. Therefore, most abnormal mammograms are false positives that require further investigations including expensive breast imaging and biopsies, which can cause psychological distress. According to the American Cancer Society (ACS), about 10% of women who have a mammogram will be called back for more tests, but only 8% to 10% of those women will need a biopsy and 80% of those biopsies turn out to be benign. Therefore, the vast majority of the women would have undergone unnecessary investigations. Our aim is to identify circulating lipid and miRNA signatures that can be used reliably as a companion diagnostic tool together with screening mammography to reduce the number of unnecessary follow-up investigations, especially invasive biopsy. In our preliminary studies, we have identified a panel of 15 plasma lipid species that were able to distinguish early stage of cancer from benign lesions with over 90% accuracy. Using a ratio based normalization method, we have also found 5 paired plasma miRNA ratios that differentiate breast cancer from benign samples with over 90% accuracy. In order to validate our existing markers and identify potential novel markers, as well as integrate lipid and miRNA markers to increase the accuracy for early detection of breast cancer, we propose the following aims: 1. Validate and test the predictive value of circulating lipid markers for early detection of breast cancer. 2. Establish circulating miRNA markers for early detection of breast cancer. 3. Integrate circulating lipid and miRNA markers for early detection of breast cancer.

Publications

  • Foox J, Nordlund J, Lalancette C, Gong T, Lacey M, Lent S, Langhorst BW, Ponnaluri VKC, Williams L, Padmanabhan KR, Cavalcante R, Lundmark A, Butler D, Mozsary C, Gurvitch J, Greally JM, Suzuki M, Menor M, Nasu M, Alonso A, Sheridan C, Scherer A, Bruinsma S, Golda G, Muszynska A, Łabaj PP, Campbell MA, Wos F, Raine A, Liljedahl U, Axelsson T, Wang C, Chen Z, Yang Z, Li J, Yang X, Wang H, Melnick A, Guo S, Blume A, Franke V, Ibanez de Caceres I, Rodriguez-Antolin C, Rosas R, Davis JW, Ishii J, Megherbi DB, Xiao W, Liao W, Xu J, Hong H, Ning B, Tong W, Akalin A, Wang Y, Deng Y, Mason CE. The SEQC2 epigenomics quality control (EpiQC) study. Genome biology. 2021 Dec 6;22(1):332. PMID: 34872606
  • Zhang F, Wu X, Chen W, Deng Y. Editorial: Cancer Informatics Toward Precision Medicine. Frontiers in medicine. 2020 Nov 25;7:576611. doi: 10.3389/fmed.2020.576611. eCollection 2020. PMID: 33330533
  • Rodriguez RM, Khadka VS, Menor M, Hernandez BY, Deng Y. Tissue-associated microbial detection in cancer using human sequencing data. BMC bioinformatics. 2020 Dec 3;21(Suppl 9):523. PMID: 33272199
  • Nakatsu K, Jijiwa M, Khadka V, Nasu M, Huo M, Deng Y. sRNAfrag: A pipeline and suite of tools to analyze fragmentation in small RNA sequencing data. bioRxiv : the preprint server for biology. 2023 Aug 21. PMID: 37662282
  • Khadka VS, Nasu M, Deng Y, Jijiwa M. Circulating microRNA Biomarker for Detecting Breast Cancer in High-Risk Benign Breast Tumors. International journal of molecular sciences. 2023 Apr 20;24. (8). PMID: 37108716
  • Rodriguez RM, Hernandez BY, Menor M, Deng Y, Khadka VS. The landscape of bacterial presence in tumor and adjacent normal tissue across 9 major cancer types using TCGA exome sequencing. Computational and structural biotechnology journal. 2020 Mar 13;18:631-641. doi: 10.1016/j.csbj.2020.03.003. eCollection 2020. PMID: 32257046
  • Fu Y, Ling Z, Arabnia H, Deng Y. Current trend and development in bioinformatics research. BMC bioinformatics. 2020 Dec 3;21(Suppl 9):538. PMID: 33272214
  • Kumar R, Deng Y, Fan JB, Wei L. Editorial: Early Detection and Diagnosis of Cancer. Frontiers in genetics. 2022 Mar 14;13:875421. doi: 10.3389/fgene.2022.875421. eCollection 2022. PMID: 35360854
  • Gong T, Borgard H, Zhang Z, Chen S, Gao Z, Deng Y. Analysis and Performance Assessment of the Whole Genome Bisulfite Sequencing Data Workflow: Currently Available Tools and a Practical Guide to Advance DNA Methylation Studies. Small methods. 2022 Mar;6(3):e2101251. Epub 2022 Jan 22. PMID: 35064762
  • Guo R, Chen Y, Borgard H, Jijiwa M, Nasu M, He M, Deng Y. The Function and Mechanism of Lipid Molecules and Their Roles in The Diagnosis and Prognosis of Breast Cancer. Molecules (Basel, Switzerland). 2020 Oct 21;25. (20). PMID: 33096860
  • Genomic Data Science Community Network, Alcazar R, Alvarez M, Arnold R, Ayalew M, Best LG, Campbell MC, Chowdhury K, Cox KEL, Daulton C, Deng Y, Easter C, Fuller K, Hakim ST, Hoffman AM, Kucher N, Lee A, Lee J, Leek JT, Meller R, Méndez LB, Méndez-González MP, Mosher S, Nishiguchi M, Pratap S, Rolle T, Roy S, Saidi R, Schatz MC, Sen SK, Sniezek J, Martinez ES, Tan FJ, Vessio J, Watson K, Westbroek W, Wilcox J, Wright C, Xie X. Diversifying the genomic data science research community. Genome research. 2022 Jul 20;32(7):1231-41. Epub 2022 Jul 20. PMID: 35858750
  • Awad CS, Deng Y, Kwagyan J, Roche-Lima A, Tchounwou PB, Wang Q, Idris MY. Summary of Year-One Effort of the RCMI Consortium to Enhance Research Capacity and Diversity with Data Science. International journal of environmental research and public health. 2022 Dec 24;20. (1). PMID: 36612607
  • Huo M, Rai SK, Nakatsu K, Deng Y, Jijiwa M. Subverting the Canon: Novel Cancer-Promoting Functions and Mechanisms for snoRNAs. International journal of molecular sciences. 2024 Mar 2;25. (5). PMID: 38474168
  • Nasu M, Khadka VS, Jijiwa M, Kobayashi K, Deng Y. Exploring Optimal Biomarker Sources: A Comparative Analysis of Exosomes and Whole Plasma in Fasting and Non-Fasting Conditions for Liquid Biopsy Applications. International journal of molecular sciences. 2023 Dec 27;25. (1). PMID: 38203541
  • Nakatsu K, Jijiwa M, Khadka V, Nasu M, Deng Y. sRNAfrag: a pipeline and suite of tools to analyze fragmentation in small RNA sequencing data. Briefings in bioinformatics. 2023 Nov 22;25. (1). PMID: 38243693
  • Chen Y, Gao Z, Mohd-Ibrahim I, Yang H, Wu L, Fu Y, Deng Y. Pan-cancer analyses of bromodomain containing 9 as a novel therapeutic target reveals its diagnostic, prognostic potential and biological mechanism in human tumours. Clinical and translational medicine. 2024 Feb;14(2):e1543. PMID: 38303608