Identification of prognostic melatonin-related lncRNA signature in tumor immune microenvironment and drug resistance for breast cancer.
Study Goal
The researchers aimed to evaluate the role of melatonin-related lncRNAs in the clinical management of BRCA patients and their immune responses.
Results Summary
A 17-melatonin-related lncRNA signature was identified, with high-signature BRCA patients showing worse prognosis and associations with immune microenvironment alterations, including higher M2 macrophage infiltration and CTLA4 expression. The signature was an independent prognostic factor and potential therapeutic target.
Population
BRCA (breast cancer) patients from the TCGA database (n=1103).
Effective Dosage
Not specified
Duration
Not specified
Interactions
None mentioned
| Intervention | Direction | Endpoint | Population | Dosage | Impact | Claim # |
|---|---|---|---|---|---|---|
melatonin-related lncRNA signature | decrease | prognosis | High-signature BRCA patients | - | had worse prognosis | #1 |
melatonin-related lncRNA signature score | neutral | prognosis | BRCA patients | - | was an independent prognostic factor | #2 |
melatonin-related lncRNA signature | neutral | mRNA processing and maturation, misfolded protein response | high-signature BRCA | - | involved in regulation of processing and maturation of mRNA and misfolded protein response | #3 |
melatonin-related lncRNA signature | increase | proportion of tumor-infiltrating M2 macrophage | high-signature BRCA | - | showed that the proportion of tumor-infiltrating M2 macrophage was significantly higher | #4 |
melatonin-related lncRNA signature | increase | expression of CTLA4 | high-signature BRCA | - | showed that the expression of CTLA4 was significantly higher | #5 |
nomogram based on the signature score and clinical characteristics | increase | prediction probability of 1-year, 3-year and 5-year survival | BRCA patients | - | was calibrated to increase prediction probability | #6 |
melatonin-related lncRNA signature | neutral | prognosis | BRCA patients | - | was considered as an independent prognostic indicator | #7 |
melatonin-related lncRNAs | neutral | tumor immune microenvironment | BRCA patients | - | were potentially associated with tumor immune microenvironment | #8 |
melatonin-related lncRNAs | neutral | therapeutic targets | BRCA patients | - | might be therapeutic targets | #9 |
BACKGROUND: Melatonin is a neurohormone involved in diverse physiological processes, including regulation of circadian rhythm, oncogenesis and immune function. More attention are focused on the molecular events surrounding the occurrence of abnormally expressed lncRNAs leading to breast cancer. The purpose of this study was to evaluate the role of melatonin-related lncRNAs in the clinical management of BRCA patients and their immune responses. METHODS: The transcriptome data and clinical data of BRCA patients were acquired from TCGA database. A total of 1103 patients were randomly assigned to either training set or validation set. A melatonin-related lncRNA signature was constructed in the training set and verified in the validation set. Functional analysis, immune microenvironment and drug resistance analysis associated to melatonin-related lncRNAs were performed by utilizing GO&KEGG, ESTIMATE and TIDE analysis. A nomogram based on the signature score and clinical characteristics was established, which was calibrated to increase prediction probability of 1-year, 3-year and 5-year survival for BRCA patients. RESULTS: BRCA patients were divided into two signature groups based on a 17-melatonin-related lncRNA signature. High-signature patients had worse prognosis than low-signature patients (p < 0.001). Univariate and multivariate Cox regression analysis proved that the signature score was an independent prognostic factor for BRCA patients. Functional analysis indicated that high-signature BRCA involved in regulation of processing and maturation of mRNA and misfolded protein response. Remarkably, immune microenvironment analysis showed that the proportion of tumor-infiltrating M2 macrophage and the expression of CTLA4 were significantly higher in high-signature BRCA. The calibration curves for the probability of invasive BRCA showed optimal agreement between the probability as predicted by the nomogram and the actual probability. CONCLUSIONS: A novel melatonin-related lncRNA signature was considered as an independent prognostic indicator for BRCA patients. Melatonin-related lncRNAs were potentially associated with tumor immune microenvironment and might be therapeutic targets for BRCA patients.