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Identification of cancer stem cell characteristics in liver hepatocellular carcinoma by WGCNA analysis of transcriptome stemness index
- Source :
- Cancer Medicine, Cancer Medicine, Vol 9, Iss 12, Pp 4290-4298 (2020)
- Publication Year :
- 2020
- Publisher :
- Wiley, 2020.
-
Abstract
- Cancer stem cells (CSCs) are characterized by self‐renewal and ‐differential potential as compared to common cancer cells and play an important role in the development and therapeutic resistance of liver hepatocellular carcinoma (LIHC). However, the specific pathogenesis of LIHC stem cells is still unclear, and the genes involved in the stemness of LIHC stem cells are currently unknown. In this study, we investigated novel biomarkers associated with LIHC and explored the expression characteristics of stem cell‐related genes in LIHC. We found that mRNA expression‐based stemness index (mRNAsi) was significantly overexpressed in liver cancer tissues. Further, mRNAsi expression in LIHC increased with the tumor pathological grade, with grade 4 tumors harboring the greatest stem cell features. Upon establishing mRNAsi scores based on mRNA expression of every gene, we found an association with poor overall survival in LIHC. Moreover, modules of interest were determined based on weighted gene co‐expression network analysis (WGCNA) inclusion criteria, and three significant modules (red, green, and brown) and 21 key genes (DCN, ECM1, HAND2, PTGIS, SFRP1, SRPX, COLEC10, GRP182, ADAMTS7, CD200, CDH11, COL8A1, FAP, LZTS1, MAP1B, NAV1, NOTCH3, OLFML2A, PRR16, TMEM119, and VCAN) were identified. Functional analysis of these 21 genes demonstrated their enrichment in pathways involved in angiogenesis, negative regulation of DNA‐binding transcription factor activity, apoptosis, and autophagy. Causal relationship with proteins indicated that the Wnt, Notch, and Hypoxia pathways are closely related to LIHC tumorigenesis. To our knowledge, this is the first report of a novel CSC biomarker, mRNAsi, to predict the prognosis of LIHC. Further, we identified 21 key genes through mRNA expression network analysis, which could be potential therapeutic targets to inhibit the stemness of cancer cells in LIHC.<br />We first reported a novel biomarker mRNAsi of stem cell index to predict the prognosis of LIHC through network analysis of the expression levels of LIHC. 21 key genes were found played important roles in LIHC stem cells. These genes could be the potential therapeutic targets for inhibiting the stemness of LIHC.
- Subjects :
- 0301 basic medicine
Cancer Research
liver hepatocellular carcinoma (LIHC)
Carcinoma, Hepatocellular
cancer stem cells (CSCs)
Angiogenesis
WGCNA analysis
Biology
medicine.disease_cause
lcsh:RC254-282
Transcriptome
03 medical and health sciences
0302 clinical medicine
Cancer stem cell
Biomarkers, Tumor
medicine
Humans
Gene Regulatory Networks
Radiology, Nuclear Medicine and imaging
Original Research
Cancer Biology
Gene Expression Profiling
Liver Neoplasms
Wnt signaling pathway
co‐expression network
mRNAsi index
lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens
medicine.disease
Gene Expression Regulation, Neoplastic
030104 developmental biology
Oncology
030220 oncology & carcinogenesis
Cancer cell
Neoplastic Stem Cells
Cancer research
biomarker
Stem cell
Liver cancer
Carcinogenesis
Subjects
Details
- ISSN :
- 20457634
- Volume :
- 9
- Database :
- OpenAIRE
- Journal :
- Cancer Medicine
- Accession number :
- edsair.doi.dedup.....04761126948ef3a5db573ec00f829345