LncRNA RP11-10E18.7 cooperates with lncRNA RP11-481C4.2 to affect the overall survival of breast cancer patients: a TCGA-based retrospective study

Transl Cancer Res. 2023 Nov 30;12(11):3156-3165. doi: 10.21037/tcr-23-1941. Epub 2023 Nov 17.

Abstract

Background: As either oncogenes or tumor suppressor genes, long non-coding RNAs (lncRNAs) have a major role in both tumorigenesis and progression of human cancers, including breast cancer (BC). However, the statistical correlation between the lncRNA-lncRNA interaction and prognosis of BC remains unclear.

Methods: We analyzed the fragments per kilobase per million (FPKM) lncRNA expression data in tumor tissue samples from 890 female patients with BC in The Cancer Genome Atlas (TCGA) between May 2021 and October 2022. The Cox proportional hazards model adjusted for age, race, clinical stage, neoadjuvant therapy, estrogen receptor (ER), and progesterone receptor (PR) was adopted to evaluate the lncRNA-lncRNA interaction regarding overall survival (OS) of BC. The multiple comparison was corrected by Bonferroni method.

Results: RP11-10E18.7×RP11-481C4.2 was significantly associated with OS of BC patients [hazard ratio (HR)interaction =1.04, 95% confidence interval (CI): 1.03-1.06, P=3.35×10-9]. Then, gene-gene interaction analysis was performed for genes co-expressed with lncRNAs. FOXA1×U2SURP (HRinteraction =1.49, 95% CI: 1.28-1.73, P=2.16×10-7) was found to have a similar interactive pattern to RP11-10E18.7×RP11-481C4.2. after classifying the patients by intersection (3.47), we observed that the effect of FOXA1 opposite in patients with different U2SURP expression level (HRhigh vs. low =0.58, 95% CI: 0.34-0.99, P=0.046 in low expression of U2SURP; HRhigh vs. low =1.56, 95% CI: 1.18-2.87, P=0.029 in high expression of U2SURP).

Conclusions: Our comprehensive study identified RP11-10E18.7×RP11-481C4.2 as a potential biomarker of BC prognosis. The results play an essential role in the impact of lncRNA-lncRNA interaction on BC survival. Our findings elucidated potential molecular mechanisms of BC progression under complex association patterns and provided potential dynamic and reversible therapeutic targets for BC patients.

Keywords: Breast cancer (BC); human; long non-coding RNA (lncRNA); overall survival (OS); prognosis.