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Long Noncoding RNAs (LncRNA-4.2, LncRNA-4.3) and Their Correlation With Hypoxia-Related Biomarkers in Breast Cancer
Hatem M Hadeed1, Maarib N Rasheed2, Ahmed AbdulJabbar Suleiman3
1Department of Clinical Laboratories Sciences, College of Pharmacy, University of Anbar, Anbar, Iraq.
The Journal of Gene Medicine
|November 5, 2025
Summary
This study reveals that long noncoding RNAs (lncRNAs) 4.2 and 4.3 show promise as biomarkers for distinguishing breast cancer stages. Hypoxia-inducible factor 1-alpha (HIF-1α) also demonstrates diagnostic potential, particularly in high-grade tumors.
Area of Science:
- Oncology
- Molecular Biology
- Biomarkers
Background:
- Breast cancer is a leading cause of cancer death in women globally.
- Long noncoding RNAs (lncRNAs) are RNA molecules with regulatory functions.
- Tumor hypoxia is common and influences cancer progression.
Purpose of the Study:
- To investigate lncRNA 4.2 and lncRNA 4.3 as potential molecular tumor markers.
- To analyze the relationship between lncRNA expression, hypoxia-inducible factor 1-alpha (HIF-1α), and clinicopathological features in breast cancer.
- To evaluate diagnostic potential of lncRNAs and HIF-1α in different breast cancer grades and treatment statuses.
Main Methods:
- Gene expression analysis of lncRNA 4.2, lncRNA 4.3, and HIF-1α.
- Study included 100 breast cancer patients categorized into low grade before treatment (LBT), low grade after treatment (LAT), high grade before treatment (HBT), and high grade after treatment (HAT) groups (n=25 each).
- A control group of 25 healthy individuals was included for comparison.
Main Results:
- lncRNA 4.2 and lncRNA 4.3 demonstrated significant discriminatory ability (AUC > 0.70) in distinguishing low-grade breast cancer before treatment (LBT) and high-grade breast cancer after treatment (HAT) from controls.
- HIF-1α showed moderate diagnostic potential (AUC > 0.60) in high-grade before treatment (HBT) and high-grade after treatment (HAT) groups.
- HIF-1α exhibited strong discriminatory ability (AUC = 0.774) specifically in the HBT group, suggesting its role in cellular stress response within this context.
Conclusions:
- lncRNA 4.2 and lncRNA 4.3 are promising biomarkers for specific breast cancer states, potentially indicating treatment response or pre-treatment conditions.
- HIF-1α serves as a valuable diagnostic marker for high-grade breast cancer, particularly before treatment, reflecting its association with tumor microenvironment stress.
- These findings highlight the potential of lncRNAs and HIF-1α in breast cancer diagnostics and understanding tumor biology.
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