Down-regulation of MEG3, PANDA and CASC2 as p53-related lncRNAs in breast cancer
Soudeh Ghafouri-Fard1, Behnoush Sohrabi2, Bashdar Mahmud Hussen3
1Department of Medical Genetics, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Abstract:
TP53 encodes a major tumor suppressor protein which blocks carcinogenesis process in a variety of tissues including breast tissue. Expression and function of this gene is regulated by a number of long non-coding RNAs (lncRNAs) among them are PANDA, MEG3 and CASC2. We measured expression of TP53 and these transcripts in a cohort of Iranian breast cancer patients. Expression levels of TP53, MEG3, CASC2 and PANDA were significantly lower in tumoral samples compared with non-tumoral samples (Posterior mean differences = -4.26, -1.66, -5.98 and -3.13, respectively; P values < 0.0001). Expression of CASC2 was higher in Her2 1+ cases compared with Her2 negative cases (Beta = 1.85, P value = 0.037). Expression levels of MEG3 and TP53 were lower in grade 2 samples compared with grade 1 (Beta = -1.86, P value = 0.006 and Beta = -2.24, P value = 0.003, respectively). There was no other significant association between expression of genes and clinical variables. CASC2 had the best performance among these genes with area under curve value of 0.78 and sensitivity and specificity values of 56.33% and 88.73%, respectively (P value < 0.0001). The current investigation supports the role of TP53-related lncRNAs in the pathogenesis of breast cancer.
Insights
Reduced expression of TP53 and related long non-coding RNAs (lncRNAs) like MEG3, CASC2, and PANDA is linked to breast cancer development. CASC2 shows potential as a diagnostic biomarker for breast cancer.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- TP53 is a critical tumor suppressor gene in breast tissue.
- Long non-coding RNAs (lncRNAs), including PANDA, MEG3, and CASC2, regulate TP53's expression and function.
- Dysregulation of these molecules is implicated in various cancers.
Purpose of the Study:
- To investigate the expression levels of TP53 and specific lncRNAs (PANDA, MEG3, CASC2) in Iranian breast cancer patients.
- To explore the association between the expression of these genes and clinical variables of breast cancer.
- To evaluate the diagnostic potential of these lncRNAs as biomarkers.
Main Methods:
- Gene expression analysis of TP53, MEG3, CASC2, and PANDA in tumoral and non-tumoral breast tissue samples.
- Statistical analysis to compare expression levels between groups and correlate with clinical parameters (Her2 status, tumor grade).
- Receiver Operating Characteristic (ROC) curve analysis to assess diagnostic performance.
Main Results:
- Significantly lower expression of TP53, MEG3, CASC2, and PANDA was observed in tumor tissues compared to non-tumoral tissues.
- CASC2 expression was higher in Her2 1+ cases versus Her2-negative cases.
- MEG3 and TP53 expression were lower in grade 2 tumors compared to grade 1.
- CASC2 demonstrated the highest diagnostic performance (AUC=0.78, sensitivity=56.33%, specificity=88.73%).
Conclusions:
- The study supports the involvement of TP53-related lncRNAs in breast cancer pathogenesis.
- Downregulation of these lncRNAs may contribute to cancer development.
- CASC2 shows promise as a potential diagnostic biomarker for breast cancer.
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