Abstract 438P
Background
Given that CRF is characterized by a lack of energy, it is postulated that mitochondrial dysfunction may contribute to its etiology. Using mitochondrial DNA (mtDNA) copy number and displacement-loop (D-loop) mutation status, this study aims to evaluate mtDNA content between fatigue subclasses, over the course of chemotherapy.
Methods
In a prospective cohort study, early-stage breast patients’ fatigue levels were assessed using the validated Multi-Dimensional Fatigue Symptom Inventory–Short Form (MFSI-SF) and their blood was drawn before, during and after treatment. Relative mtDNA copy number was determined via real-time quantitative polymerase chain reaction while mitochondrial genome was sequenced directly for D-loop mutations at nucleotide positions 303, 489 and 514. Subclasses of extent of fatigue was derived using latent class analysis, based on magnitude of change in sub-domain scores after treatment, with respect to baseline. Clinically relevant factors that differentiate the identified subclasses were then compared between the fatigued groups.
Results
A total of 133 patients (mean age ± SD: 51.2 ± 8.8 years, median mtDNA: 71.0) were classified into two fatigue subclasses: mild fatigue (75.2%) and fatigued group (24.8%) respectively. Based on mtDNA trajectory, patients who are predisposed to CRF started off with lower baseline values and experienced slower recovery. Median mtDNA content was reduced over 12 weeks after initiation of chemotherapy (p < 0.001) and was reported to be consistently lower in fatigued group (T2: 48.0 vs 56.0; T3: 61.4 vs 66.0) although the difference was not found to be statistically significant. The proportion of patients with D-loop mutation status was comparable between fatigued group and mild fatigue (303: 81.8% vs 73.0%, 489: 45.5% vs 47.0% and 514: 45.5% vs 53.0%). However, no association was reported between mtDNA levels over time or D-loop mutation with CRF status.
Conclusions
mtDNA content and D-loop mutation status do not sufficiently differentiate fatigue subclasses, suggesting that future research may be needed to study the differential expression of mitochondrial dysfunction-related genes and the pathways they may perturb.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
National University of Singapore.
Funding
National Medical Research Council.
Disclosure
All authors have declared no conflicts of interest.
Resources from the same session
458P - Mutation tracking in circulating tumour DNA predicts relapse in completely resected EGFR-mutated NSCLC
Presenter: Martin Filipits
Session: Poster display session
Resources:
Abstract
460P - Mendelian randomization study showed no causality between metformin use and lung cancer risk
Presenter: Jiayi Shen
Session: Poster display session
Resources:
Abstract
461P - Blood trace minerals and lung cancer: A Mendelian randomization study
Presenter: Wei Xian
Session: Poster display session
Resources:
Abstract
463P - Prediction of invasiveness in lung adenocarcinoma using machine learning algorithm based on 3D-CT imaging
Presenter: Yusuke Saeki
Session: Poster display session
Resources:
Abstract
459P - Fish intake, dietary polyunsaturated fatty acids, and lung cancer: systematic review and dose-response meta-analysis of 1.7 million men and women
Presenter: Chao Cao
Session: Poster display session
Resources:
Abstract
462P - Usefulness for prevention of postoperative cerebrovascular complications in patients with lung cancer using carotid ultrasonography
Presenter: Sadanori Takeo
Session: Poster display session
Resources:
Abstract
468P - Histological type analysis of 10-year follow-up of WJTOG0105: A phase III study comparing second- and third-generation regimens with concurrent thoracic radiotherapy in unresectable stage III non-small cell lung cancer
Presenter: Masahiro Tsuboi
Session: Poster display session
Resources:
Abstract
469P - Comparison of combined chemoradiotherapy regimens; Paclitaxel plus carboplatin and cisplatin plus etoposide for locally advanced non-small cell lung cancer: A randomised phase III trial
Presenter: Alper Ata
Session: Poster display session
Resources:
Abstract
472P - Integration of expression rate and absolute cell counts of PD-1+ stromal tumour-infiltrating lymphocytes: Prognostic significance in esophageal squamous cell carcinoma
Presenter: Qingkun Song
Session: Poster display session
Resources:
Abstract
467P - The free-circulating mtDNA copies number in plasma of patients with NSCLC
Presenter: Olga Bulgakova
Session: Poster display session
Resources:
Abstract