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Survival analysis for long noncoding RNAs identifies TP53TG1 as an antioncogenic target for the breast cancer
Mei Shao1, Huali Ma2, Xing Wan3
1Department of Neurosurgery, Linyi People's Hospital, Linyi, Shandong, China.
Abstract:
Breast carcinoma is one of the most commonly diagnosed tumors and also one of the deadliest cancers in the female. Long noncoding RNAs (lncRNAs) are emerging as novel targets and biomarkers for breast cancer diagnosis and treatment. In this study, we aimed to study the lncRNAs associated with the outcomes in patients using the breast invasive carcinoma datasets from The Cancer Genome Atlas. The Cox proportional hazards regression model was fitted to each lncRNA. Hierarchy clustering was carried out using these survival-related lncRNAs and the log-rank test was carried out for the clustered groups. DNA methylation status was utilized to identify the lncRNAs regulated by epigenetics. Finally, the coexpressed messenger RNA with the potential lncRNAs were utilized to study the possible functions and mechanisms of lncRNAs. In total, 182 lncRNAs had an impact on the survival time of the patients with a cutoff <0.01. The patients were clustered into three groups using these survival-related genes, which performed significantly different prognosis. Two lncRNAs, which were significantly correlated with the outcomes of breast cancer and were regulated by methylation status, were obtained. These two lncRNAs were TP53TG1 and RP5-1061H20.4. We proposed that TP53TG1 was activated by the wild-type TP53 and performed an impact on the PI3Ks family by binding YBX2 in breast cancer.
Insights
This study identified 182 long noncoding RNAs (lncRNAs) impacting breast cancer patient survival. Two key lncRNAs, TP53TG1 and RP5-1061H20.4, regulated by epigenetics, were found to significantly correlate with patient outcomes.
Area of Science:
- Oncology
- Genomics
- Molecular Biology
Background:
- Breast carcinoma is a leading cause of cancer death in women.
- Long noncoding RNAs (lncRNAs) show promise as diagnostic and therapeutic targets for breast cancer.
Purpose of the Study:
- To identify lncRNAs associated with patient outcomes in breast invasive carcinoma.
- To explore epigenetic regulation and functional mechanisms of survival-related lncRNAs.
Main Methods:
- Utilized The Cancer Genome Atlas (TCGA) breast invasive carcinoma dataset.
- Applied Cox regression, hierarchical clustering, and log-rank tests for survival analysis.
- Investigated DNA methylation and coexpressed messenger RNAs for epigenetic regulation and function.
Main Results:
- Identified 182 survival-related lncRNAs (p < 0.01) impacting patient survival time.
- Clustered patients into three groups with significantly different prognoses based on lncRNAs.
- Pinpointed TP53TG1 and RP5-1061H20.4 as key methylation-regulated lncRNAs linked to breast cancer outcomes.
Conclusions:
- TP53TG1 and RP5-1061H20.4 are significant prognostic biomarkers in breast cancer.
- TP53TG1 may impact the PI3K pathway via YBX2 binding, potentially activated by wild-type TP53.
- Epigenetic regulation, specifically DNA methylation, plays a role in lncRNA function in breast cancer progression.
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