Identification of cancer prognosis-associated functional modules using differential co-expression networks

Abstract

The rapid accumulation of cancer-related data owing to high-throughput technologies has provided unprecedented choices to understand the progression of cancer and discover functional networks in multiple cancers. Establishment of co-expression networks will help us to discover the systemic properties of carcinogenesis features and regulatory mechanisms of multiple cancers. Here, we proposed a computational workflow to identify differentially co-expressed gene modules across 8 cancer types by using combined gene differential expression analysis methods and a higher-order generalized singular value decomposition. Four co-expression modules were identified; and oncogenes and tumor suppressors were significantly enriched in these modules. Functional enrichment analysis demonstrated the significantly enriched pathways in these modules, including ECM-receptor interaction, focal adhesion and PI3K-Akt signaling pathway. The top-ranked miRNAs (mir-199, mir-29, mir-200) and transcription factors (FOXO4, E2A, NFAT, and MAZ) were identified, which play an important role in deregulating cellular energetics; and regulating angiogenesis and cancer immune system. The clinical significance of the co-expressed gene clusters was assessed by evaluating their predictability of cancer patients’ survival. The predictive power of different clusters and subclusters was demonstrated. Our results will be valuable in cancer-related gene function annotation and for the evaluation of cancer patients’ prognosis.

m6A RNA methylation regulators can contribute to malignant progression and impact the prognosis of bladder cancer

“…The high recurrence rate and drug resistance make the treatment of BC difficult in clinical research. Studies have shown that multiple genes always interact with each other to regulate the development of tumors [35]. m6A RNA methylation regulators play an important role in the development of cancer [36].…”

Expressions of m6A RNA methylation regulators and their clinical predictive value in cervical squamous cell carcinoma and endometrial adenocarcinoma

“…With the development of retrofitted radiation therapy and targeted therapy, the 5‐year survival rate of patients has improved, but local recurrence and drug resistance brought difficulties in CESC treatment. Studies have shown that cancer progression can be regulated by the interaction of multiple genes, 18 and m6A RNA methylation regulators play significant roles in tumourigenesis and development 19 . Thus, it is necessary to explore the effects of m6A RNA methylation regulators on CESC progression.…”

Upregulation of HOXA11 during the progression of lung adenocarcinoma detected via multiple approaches

“…Hence, the present study attempted to predict the potential mechanisms of the role of HOXA11 in LUAD in silico . With the development of high-throughput sequencing and novel computational approaches, accumulating evidence has proven that multiple genes always function together and then regulate tumor initiation and progression ( 32 ). To investigate the function of HOXA11, the cBioPortal and MEM databases were used in the present study to identify the genes co-expressed with HOXA11.…”