Individualized Prediction of Survival by a 10-Long Non-coding RNA-Based Prognostic Model for Patients With Breast Cancer

Abstract

Deregulations of long non-coding RNAs (lncRNAs) have been implicated in the progression of breast cancer (BC). However, the prognostic values of those lncRNAs in BC remain elusive. This study aimed at constructing a lncRNA-based prognostic model to improve the clinical management of BC. Systematic investigation of lncRNA expression profiles and clinical data from The Cancer Genome Atlas (TCGA) database were utilized to establish a 10-lncRNA signature. The prognostic signature efficiently discriminated patients with significantly different prognosis regardless of intrinsic molecular subtypes and tumor-node-metastasis (TNM) stage. A combined model was constructed by multivariate Cox proportional hazards regression (CPHR) analysis, which combined the lncRNA-based signature with certain clinical risk factors (TNM stage, age, and human epidermal growth factor receptor 2 status). This model predicted a survival probability that closely corresponds to the actual survival probability. With respect to the entire set, the time-dependent receiver-operating characteristic curves revealed that the area under the curve of this model was the highest than any of the clinical risk factors. Moreover, functional enrichment analysis indicated that the molecular signature was mainly involved in DNA replication, which was firmly related to BC tumorigenesis. Consistent with the discovery, the knockdown of LHX1-DT, one of the 10 prognostic lncRNAs, attenuated the proliferation of BC cells in vitro and in vivo. Taken together, our study constructed a novel 10-lncRNA signature for prediction prognosis, and the signature-based model could provide new insight into accurate management of BC patients.

CCIVR2 facilitates comprehensive identification of both overlapping and non-overlapping antisense transcripts within specified regions

“…PCAT6 enhances proliferation and EMT in gastric cancer (GC) 29 , and KDM5B enhances EMT in lung cancer cell line, A549 30 , and in hepatocellular carcinoma 31 . LHX1 is involved in modulating EMT induction in uterine corpus endometrial carcinoma 32 , and LHX1-DT enhances cell proliferation in breast cancer 33 . These coordinated gene expression changes that were up-regulated by TGFβ stimulation were also confirmed by qRT-PCR (Fig.…”

Development and validation of a nomogram to predict survival for advanced male breast cancer

“…About 20%–30% of breast cancer patients with early age will finally develop metastatic lesions (Early Breast Cancer Trialists' Collaborative G, 2005; Xie et al, 2019). For female patients, plenty of studies had investigated various markers to monitor disease change as to react timely (Huang, Hua, et al, 2020; Wang et al, 2020; Yang et al, 2020). However, there were a few researches about predictive model for metastatic male patients.…”

LncRNA CASC9 activated by STAT3 promotes the invasion of breast cancer and the formation of lymphatic vessels by enhancing H3K27ac‐activated SOX4

“…Long noncoding RNAs (lncRNAs) are noncoding RNAs that are over 200 nucleotides in length and are attracting increasing attention due to their biological effects on a series of cellular processes by affecting gene expression via transcriptional, posttranscriptional, and epigenetic regulation 7 . Emerging reports have indicated that dysregulation of lncRNAs are involved in the occurrence, recurrence, and metastasis of BC 8 . For example, lncRNA H19 functioned as an oncogenic gene in BC by facilitating epithelial‐mesenchymal transition (EMT) invasion and migration by upregulating Snail lncRNA TTN‐AS1 was significantly overexpressed in the tissues and cells of triple‐negative BC in clinical tissues and cell lines, and its knockdown suppressed the proliferative, migratory, and invasive abilities of tumor cells 9 .…”

“…7 Emerging reports have indicated that dysregulation of lncRNAs are involved in the occurrence, recurrence, and metastasis of BC. 8 For example, lncRNA H19 functioned as an oncogenic gene in BC by facilitating epithelial-mesenchymal transition (EMT) invasion and migration by upregulating Snail lncRNA TTN-AS1 was significantly overexpressed in the tissues and cells of triplenegative BC in clinical tissues and cell lines, and its knockdown suppressed the proliferative, migratory, and invasive abilities of tumor cells. 9 Cancer susceptibility candidate 9 (CASC9) was identified as a tumor-promoting lncRNA in several human cancers, such as esophageal cancer, lung adenocarcinoma, and BC.…”