High-resolution metabolomics of diffuse large B-cell and follicular lymphomas: A pilot case-control study Open Access

Shih, Brandon E (Spring 2021)

Permanent URL: https://etd.library.emory.edu/concern/etds/fn107023c?locale=en


Background: Non-Hodgkin lymphoma (NHL) is a common cancer within the US, accounting for about 4% of all new cancer cases and 3% of all cancer deaths. The etiology of NHL is poorly understood with no useful biomarker to aid early diagnosis. To address this gap, we conducted a comprehensive metabolome-wide association study (MWAS) to identify metabolomic perturbations and pathways associated with NHL risk.

Methods: We used previously collected serum samples from a large population-based case-control study of incident NHL across six counties within the San Francisco Bay Area conducted between 2001 and 2005. For our pilot study, serum samples were available for 142 NHL cases frequency and matched to 142 controls by age and sex. Metabolome perturbations associated with the risk for two main NHL subtypes, diffuse large B-cell lymphoma (DLBCL, n = 75) and follicular lymphoma (FL, n = 67), were assessed with an untargeted HRM workflow using liquid chromatography-high resolution mass spectrometry with HILIC positive and C18 negative chromatography columns, followed by conditional logistic regression, pathway enrichment analysis, and chemical annotation.

Results: After HRM data processing and cleaning, 7,061 and 5,633 metabolic features were identified in serum samples with positive and negative ionization modes, respectively. Twenty-one metabolic pathways and ten metabolic pathways were found to be associated with DLBCL and FL risk, respectively. The only metabolic pathway associated with risk in both subtypes was tryptophan metabolism pathway. We confirmed thirteen metabolites within tryptophan pathways associated with either DLBCL or FL risk. Additionally, we confirmed nine metabolites within tyrosine metabolism associated with FL risk.

Discussion: The thirteen metabolites identified within tryptophan pathways suggest they might contribute to the suppression of anti-tumor immune responses, creating a favorable environment for tumor cells. The nine metabolites within tyrosine metabolism may also suggest a similar contribution to innate immune response and other important biological functions. Identification of metabolome perturbations and pathways associated with NHL risk from this study may contribute to the development of novel biomarkers for risk of NHL.

Table of Contents

Chapter I: Background/Literature Review 1

Chapter II: Manuscript 6

A.   Abstract 6

B.   Introduction 7

C.   Methods 8

D.   Results 11

E.    Discussion 13

Strengths and Weaknesses 15

F.    References 16

G.   Tables 22

Table 1 22

Table 2 23

Table 3 24

Table 4 24

Table 5 24

H.   Figures 25

Figure 1 25

Figure 2 26

Figure 3 27

Figure 4 29

Figure 5 30

Chapter III: Future Directions 31

About this Master's Thesis

Rights statement
  • Permission granted by the author to include this thesis or dissertation in this repository. All rights reserved by the author. Please contact the author for information regarding the reproduction and use of this thesis or dissertation.
  • English
Research Field
Committee Chair / Thesis Advisor
Committee Members
Last modified

Primary PDF

Supplemental Files