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Sex-Specific miRNA Differences in Liquid Biopsies from Subjects with Solid Tumors and Healthy Controls
Elena Tomeva1, Ulrike D B Krammer1,2, Olivier J Switzeny1
1HealthBioCare GmbH, A-1090 Vienna, Austria.
Epigenomes
|January 17, 2023
Summary
Epigenetic mechanisms, especially microRNAs (miRNAs), show sex-specific differences in cancer. These differences in miRNA expression and correlation with cancer stage highlight the need to consider sex in epigenetic biomarker research.
Area of Science:
- Epigenetics and molecular oncology
- Sex-based biological differences in disease
- Biomarker discovery in cancer
Background:
- Epigenetic dysregulation is key in cancer, but sex-specific variations exist.
- MicroRNAs (miRNAs) are crucial epigenetic regulators with potential sex-dependent roles in cancer.
- Understanding these sex-specific epigenetic differences is vital for accurate cancer diagnosis and treatment.
Purpose of the Study:
- To investigate sex-specific differences in cell-free DNA methylation and miRNA expression in healthy individuals and cancer patients.
- To identify specific miRNAs exhibiting distinct expression patterns between males and females across various solid tumors.
- To explore sex-specific correlations between miRNA expression and cancer stage.
Main Methods:
- Quantitative PCR (qPCR) was used to analyze 12 cell-free DNA methylation targets and 48 miRNAs in plasma samples.
- Samples were collected from healthy controls and patients with bladder, brain, colorectal (CRC), lung, stomach, pancreas, and liver cancers.
- Statistical analyses for sex-specific differences were performed on healthy subjects, CRC, stomach/pancreas cancer patients, and all cancer patients combined, considering sample size and sex distribution.
Main Results:
- Several miRNAs showed opposing expression patterns between sexes in healthy individuals (e.g., miR-17-5p, miR-26b-5p) and across different cancer types (CRC, stomach cancer).
- Common miRNAs (e.g., miR-126-3p, miR-21-5p, miR-92a-3p) displayed sex-specific expression differences when all cancer patients were analyzed together.
- Sex-specific correlations between miRNA expression and cancer stage were identified in both women (miR-27a-3p) and men (miR-17-5p, miR-20a-5p).
Conclusions:
- Epigenetic regulation, particularly by miRNAs, plays a complex and distinct role in cancer that is dependent on both health status and sex.
- The same miRNAs can have varied effects in different tissues and opposing effects between biological sexes.
- Sex should be a critical consideration in the development and application of miRNA-based cancer biomarker research.
