Development and Validation of a Novel Hypoxia-Related Long Noncoding RNA Model With Regard to Prognosis and Immune Features in Breast Cancer

Abstract

Background: Female breast cancer is currently the most frequently diagnosed cancer in the world. This study aimed to develop and validate a novel hypoxia-related long noncoding RNA (HRL) prognostic model for predicting the overall survival (OS) of patients with breast cancer.Methods: The gene expression profiles were downloaded from The Cancer Genome Atlas (TCGA) database. A total of 200 hypoxia-related mRNAs were obtained from the Molecular Signatures Database. The co-expression analysis between differentially expressed hypoxia-related mRNAs and lncRNAs based on Spearman’s rank correlation was performed to screen out 166 HRLs. Based on univariate Cox regression and least absolute shrinkage and selection operator Cox regression analysis in the training set, we filtered out 12 optimal prognostic hypoxia-related lncRNAs (PHRLs) to develop a prognostic model. Kaplan–Meier survival analysis, receiver operating characteristic curves, area under the curve, and univariate and multivariate Cox regression analyses were used to test the predictive ability of the risk model in the training, testing, and total sets.Results: A 12-HRL prognostic model was developed to predict the survival outcome of patients with breast cancer. Patients in the high-risk group had significantly shorter median OS, DFS (disease-free survival), and predicted lower chemosensitivity (paclitaxel, docetaxel) compared with those in the low-risk group. Also, the risk score based on the expression of the 12 HRLs acted as an independent prognostic factor. The immune cell infiltration analysis revealed that the immune scores of patients in the high-risk group were lower than those of the patients in the low-risk group. RT-qPCR assays were conducted to verify the expression of the 12 PHRLs in breast cancer tissues and cell lines.Conclusion: Our study uncovered dozens of potential prognostic biomarkers and therapeutic targets related to the hypoxia signaling pathway in breast cancer.

A lactate-related LncRNA model for predicting prognosis, immune landscape and therapeutic response in breast cancer

“…In our study, the AUCs of the signatures at 3-, 5-, and 10-year were 0.7536, 0.7229, and 7,703, respectively, significantly higher than most hallmark predictive models. Table 1 showed that the 3-, 5-, and 10-year AUCs of another 7 lncRNA prognostic signatures, namely, the ferroptosis- and Immune-related lncRNA signature (3-, 5-, and 10-year AUCs: 0.71, 0.63, and 0.68) ( Wei et al, 2022 ) and necroptosis-related lncRNA signature (3-, 5-, and 10-year AUCs: 0.643, 0.641, and 0.694) ( Chen et al, 2022 ) had lower AUCs than ours; while the 12 hypoxia-related lncRNA signature (3-, 5-, and 10-year AUCs: 0.727, 741, and 0.786) ( Gu et al, 2021 ) were comparable to the predictive capabilities of our predictive model, and our signature stand out with a clear advantage in predicting the short-term survival of BC patients. We also listed the other signatures that focus more on short-term (3- and 5-year survival) survival.…”

An Immune-Related Long Noncoding RNA Pair as a New Biomarker to Predict the Prognosis of Patients in Breast Cancer

“…After analyzing the contents of infiltrating immune cells, the Wilcoxon signed-rank test was used to evaluate the differences between the high-risk and low-risk groups, designed by MIR4435-2HG|U62317.1, with regard to tumor-infiltrating immune cells, utilizing a boxplot to depict ( Li C. et al, 2021 ). And Spearman correlation analysis was used to evaluate the relationship between the riskScore and the tumor-infiltrating immune cells, utilizing a lollipop chart to demonstrate the resulting correlation coefficient ( Gu et al, 2021 ). This procedure was carried out with the ggplot2 package in R and p < 0.05 as an identifying threshold.…”

Identification of a hypoxia-suppressed lncRNA RAMP2-AS1 in breast cancer

“…It has been widely acknowledged that hypoxia is an important cancer characteristic in multiple solid tumors, including breast cancer [ 3 ]. Several lines of evidence have confirmed close correlation of hypoxia with invasion [ 4 ], metastasis [ 5 ], inflammation [ 6 ] and poor prognosis [ 7 ] in breast cancer.…”