Intravenous leiomyomatosis is inclined to a solid entity different from uterine leiomyoma based on RNA‐seq analysis with RT‐qPCR validation

Abstract

IntroductionIntravenous leiomyomatosis (IVL) is currently regarded as a special variant of the common uterine leiomyoma (LM). Though IVL shows a similar histological morphology to LM, IVL is characterized by unique intravenous growth patterns and low‐grade malignant potential, which are quite different from LM. There are currently few studies underlying the molecular alterations of IVL, though this information is important for understanding the pathogenesis of the disease, and for identifying potential biomarkers.MethodWe carried out a high‐throughput whole transcriptome sequencing of tumor and normal tissue samples from five IVL patients and five LM patients and compared the differentially expressed genes (DEGs) between IVL and leiomyoma. We performed multiple different enrichment and target analyses, and the expression of selected DEGs was validated using RT‐qPCR in formalin‐fixed samples.ResultsOur study identified substantial different genes and pathways between IVL and LM, and functional enrichment analyses found several important pathways, such as angiogenesis and antiapoptosis pathways, as well as important related genes, including SH2D2A, VASH2, ADAM8, GATA2, TNF, and the lncRNA GATA6‐AS1, as being significantly different between IVL and LM (P = .0024, P = .0195, P = .0212, P = .0435, P = .0401, and P = .0246, respectively). CXCL8, LIF, CDKN2A, BCL2A1, COL2A1, IGF1, and HMGA2 were also differently expressed between IVL and LM groups, but showed no statistical difference (P = .2409, P = .1773, P = .0596, P = .2737, P = .1553, P = .1045, and P = .1847, respectively) due to the large differences among individuals. Furthermore, RT‐qPCR results for five selected DEGs in IVL tissues and adjacent nontumor tissues were mainly consistent with our sequencing results.ConclusionOur results indicated that IVL may be a solid entity that is unique and different from LM, proving consistent with previous studies. Furthermore, we identified DEGs, particularly within angiogenesis and antiapoptosis pathway‐related genes that may play crucial roles in the development and pathogenesis of IVL and may be potential specific biomarkers.

Proteomic profiling identifies co-regulated expression of splicing factors as a characteristic feature of intravenous leiomyomatosis

“…IVLM is a rare benign smooth muscle tumour with quasi-malignant clinical behaviour. Previous profiling studies characterising its molecular features have focused on DNA copy number and transcriptomic alterations [9,11,13,14]. Here we performed the first proteome level analysis of IVLM and compare it to other smooth muscle tumours including uLM, stLM and BML.…”

“…Previous studies have undertaken comparative analysis of the molecular features of IVLM versus uLM to gain a better understanding of its underlying biology as well as the relationship between the two entities [9][10][11][12][13][14][15]. Some of the system-wide comprehensive profiling studies that have been reported include array comparative genomic profiling (aCGH) and transcriptomic analysis [9,11,13,14]. Collectively, these focused and system-wide studies indicate that IVLM share some cytogenetic and protein expression features with uLM (e.g.…”

Identification of Novel Serum Metabolic Biomarkers as Indicators in the Progression of Intravenous Leiomyomatosis: A High Performance Liquid Chromatography-Tandem Mass Spectrometry-Based Study

“…At present, an increasing number of studies have begun to focus on finding potential regulatory factors and biomarkers that affect the occurrence and progression of the disease, which are of great significance for the diagnosis, treatment and prognosis of IVL. Based on RNA sequencing analysis and reverse transcription-quantitative PCR, Wang W. et al (2020) verified that IVL tended to be a solid tumor differing from uterine leiomyoma and found that CDKN2A , BCL2A1 , and angiogenesis-related gene CXCL8 might be new specific biomarkers of IVL. However, these findings remained to be further confirmed by larger samples ( Wang W. et al, 2020 ).…”

“…Based on RNA sequencing analysis and reverse transcription-quantitative PCR, Wang W. et al (2020) verified that IVL tended to be a solid tumor differing from uterine leiomyoma and found that CDKN2A , BCL2A1 , and angiogenesis-related gene CXCL8 might be new specific biomarkers of IVL. However, these findings remained to be further confirmed by larger samples ( Wang W. et al, 2020 ). In another study, molecular analysis of 17 cases of IVL revealed that MED12 mutations, MSI and LOH were inconsistent among patients with either uterine or extrauterine IVL.…”

Proteomic Profiling Identifies Co-Regulated Expression of Splicing Factors as a Characteristic Feature of Intravenous Leiomyomatosis

“…Previous studies have undertaken comparative analyses of the molecular features of IVLM versus uLM to gain a better understanding of its underlying biology as well as the relationship between the two entities [ 9 , 10 , 11 , 12 , 13 , 14 , 15 ]. Some of the system-wide comprehensive profiling studies that have been reported include array comparative genomic profiling (aCGH) and transcriptomic analysis [ 9 , 11 , 13 , 14 ].…”