A two-phase comprehensive NSCLC prognostic study identifies lncRNAs with significant main effect and interaction.
Jing Zhu1, Jinxing Guan2, Xinyu Ji2
1Department of Oncology, The Affiliated Jiangning Hospital of Nanjing Medical University, 169 Hushan Road, No. 2 Building, 212 East Ward, Nanjing, 211100, Jiangsu, China.
Molecular Genetics and Genomics : MGG
|February 26, 2022
Summary
This study identifies key long noncoding RNAs (lncRNAs) and their interactions that impact non-small-cell lung cancer (NSCLC) survival. Findings reveal specific lncRNAs and lncRNA pairs as robust prognostic markers for NSCLC patients.
Area of Science:
- Oncology
- Genomics
- Bioinformatics
Background:
- Long noncoding RNAs (lncRNAs) play crucial roles in the physiological regulation of various malignant tumors, including non-small-cell lung cancer (NSCLC).
- Comprehensive evaluation of both lncRNA-lncRNA interactions and individual lncRNA effects on NSCLC overall survival remains limited.
Purpose of the Study:
- To conduct a large-scale, two-phase study to identify lncRNAs and their interactions significantly associated with NSCLC prognosis.
- To provide population-level evidence for lncRNA's role in NSCLC survival for future functional investigations.
Main Methods:
- Utilized a two-phase design with 604 NSCLC patients (discovery) from The Cancer Genome Atlas and 839 patients (validation) from Gene Expression Omnibus.
- Employed a two-step strategy: weighted random forest (Ranger) for screening and Cox proportional hazards model for testing lncRNA effects on survival.
- Candidate lncRNAs and interactions were validated in an independent cohort to confirm significance.
Main Results:
- Identified 19 candidate lncRNAs in the discovery phase; five lncRNAs showed significant main effects and one lncRNA-lncRNA pair showed a significant interaction effect on NSCLC survival (FDR-q ≤ 0.05).
- Validated findings confirmed one lncRNA (ENSG00000227403.1) as robustly associated with NSCLC prognosis (HRdiscovery=0.90, P=1.20×10⁻³; HRvalidation=0.94, P=4.11×10⁻³).
- A significant interaction effect was observed for a pair of lncRNAs (ENSG00000267121.4 and ENSG00000272369.1) on NSCLC survival (HRdiscovery=1.12, P=3.07×10⁻⁴; HRvalidation=1.11, P=0.0397).
Conclusions:
- This study provides robust, population-level evidence for the prognostic significance of specific lncRNAs and their interactions in NSCLC.
- The identified lncRNA (ENSG00000227403.1) and lncRNA pair (ENSG00000267121.4/ENSG00000272369.1) represent potential biomarkers for NSCLC patient outcomes.
- These findings warrant further functional studies to elucidate the mechanisms underlying lncRNA's role in NSCLC progression and survival.
Related Concept Videos
02:39lncRNA - Long Non-coding RNAs
9.0K
In humans, more than 80% of the genome gets transcribed. However, only around 2% of the genome codes for proteins. The remaining part produces non-coding RNAs which includes ribosomal RNAs, transfer RNAs, telomerase RNAs, and regulatory RNAs, among other types. A large number of regulatory non-coding RNAs have been classified into two groups depending upon their length – small non-coding RNAs, such as microRNA, which are less than 200 nucleotides in length, and long non-coding RNA...
9.0K
01:21Cancer Survival Analysis
473
Cancer survival analysis focuses on quantifying and interpreting the time from a key starting point, such as diagnosis or the initiation of treatment, to a specific endpoint, such as remission or death. This analysis provides critical insights into treatment effectiveness and factors that influence patient outcomes, helping to shape clinical decisions and guide prognostic evaluations. A cornerstone of oncology research, survival analysis tackles the challenges of skewed, non-normally...
473