Identification of two molecular subtypes of dysregulated immune lncRNAs in ovarian cancer

Abstract

Long non-coding RNA (lncRNA) has increasingly been identified as a key regulator in pathologies such as cancer. Multiple platforms were used for comprehensive analysis of ovarian cancer to identify molecular subgroups. However, lncRNA and its role in mapping the ovarian cancer subpopulation are still largely unknown. RNA-sequencing and clinical characteristics of ovarian cancer were acquired from The Cancer Genome Atlas database (TCGA). A total of 52 lncRNAs were identified as aberrant immune lncRNAs specific to ovarian cancer. We redefined two different molecular subtypes, C1(188) and C2(184 samples), in “iClusterPlus” R package, among which C2 grouped ovarian cancer samples have higher survival probability and longer median survival time ( P <0.05) with activated IFN-gamma response, Wound Healing and Cytotoxic lymphocytes signal; 456 differentially expressed genes were acquired in C1 and C2 subtypes using limma (3.40.6) package, among which 419 were up-regulated and 37 were down-regulated, in TCGA dataset. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) functional enrichment analysis revealed that these genes were actively involved in ECM-receptor interaction, PI3K-Akt signaling pathway interaction KEGG pathway. Compared with the existing immune subtype, the Cluster2 sample showed a substantial increase in the proportion of the existing C2 immune subtype, accounting for 81.37%, which was associated with good prognosis. Our C1 subtype contains only 56.49% of the existing immune C1 and C4, which also explains the poor prognosis of C1. Furthermore, 52 immune-related lncRNAs were used to divide the TCGA-endometrial cancer and cervical cancer samples into two categories, and C2 had a good prognosis. The differentially expressed genes were highly correlated with immune-cell-related pathways. Based on lncRNA, two molecular subtypes of ovarian cancer were identified and had significant prognostic differences and immunological characteristics.

Computational approaches for discovering significant microRNAs, microRNA-mRNA regulatory pathways, and therapeutic protein targets in endometrial cancer

“…Remarkably, stromal cell activity is also deregulated by ECM abnormalities which promotes inflammation as well as angiogenesis resulting in the formation of cancer microenvironments. The ECM-receptor interaction signal pathway has also been identified as a contributor to cancer progression with low survival rate in many gynecological malignancies including endometrial cancer, breast cancer and ovarian cancer ( Bao et al, 2019 ; Liu et al, 2021 ; Yadav et al, 2020 ). In this study, the expression of COL3A1 , COL5A1 and COL5A2 were downregulated in EC, are of the collagen family, and they interact with elements of the extracellular matrix (ECM) including matrix metalloproteinases, tyrosine kinase receptors, integrins, and signaling pathways to affect the behavior and activity of cancer cells.…”

The joint role of methylation and immune-related lncRNAs in ovarian cancer: Defining molecular subtypes and developing prognostic signature

“…By analyzing the unique categories and subclasses of TIME in patients' tumors, the ability to predict and guide immunotherapeutic responses could be improved, and new therapeutic targets will be revealed [39] . The OC classification based on immune-related lncRNAs [40] and the glioma prognostic model based on m6A/m5C/m1A/m7G related lncRNAs have been reported [41] . M6A/m5C/m1A/m7G-related lncRNA has not yet been applied to explore the classification of OC.…”

Immune-Related Long Non-coding RNA Constructs a Prognostic Signature of Ovarian Cancer

“…Liang et al [32] used weighted gene co-expression network analysis (WGCNA) and found that the expression levels of 4 lncRNAs could be used as independent immune prognostic factors for OC. Liu et al [33] identified 52 lncRNAs as ovarian cancer-specific immune lncRNA and redefined two different molecular subtypes. Different from the existing researches, we established a Fig.…”