Study of Gene Expression Profiles of Breast Cancers in Indian Women

Malvia, Shreshtha; Bagadi, Sarangadhara Appala Raju; Pradhan, Dibyabhaba; Chintamani, Chintamani; Bhatnagar, Amar; Arora, Deepshikha; Sarin, Ramesh; Saxena, Sunita

doi:10.1038/s41598-019-46261-1

Cited by 39 publications

(30 citation statements)

References 103 publications

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“…We confirmed that 5 genes, including COL11A1 , GFAP , FGF5 , CD300LG , and IGFL2 , were co-expressed with WT1 . In agreement with our results, the high expressions of WT1 , COL11A1 , and FGF5 in BC tumors have also been reported in previous literatures ( Huang, Wang & Yang, 2018 ; Li, Kong & Zou, 2017a ; Malvia et al, 2019 ). WT1 overexpression could promote ERK1/2 phosphorylation and thus decreasing E-cadherin expression and enhance EMT (epithelial-to-mesenchymal transition) ( Han et al, 2020 ).…”

Section: Discussionsupporting

confidence: 94%

Comprehensive analysis based on DNA methylation and RNA-seq reveals hypermethylation of the up-regulated WT1 gene with potential mechanisms in PAM50 subtypes of breast cancer

Ren

Tang

Lan

2021

PeerJ

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Background Breast cancer (BC), one of the most widespread cancers worldwide, caused the deaths of more than 600,000 women in 2018, accounting for about 15% of all cancer-associated deaths in women that year. In this study, we aimed to discover potential prognostic biomarkers and explore their molecular mechanisms in different BC subtypes using DNA methylation and RNA-seq. Methods We downloaded the DNA methylation datasets and the RNA expression profiles of primary tissues of the four BC molecular subtypes (luminal A, luminal B, basal-like, and HER2-enriched), as well as the survival information from The Cancer Genome Atlas (TCGA). The highly expressed and hypermethylated genes across all the four subtypes were screened. We examined the methylation sites and the downstream co-expressed genes of the selected genes and validated their prognostic value using a different dataset (GSE20685). For selected transcription factors, the downstream genes were predicted based on the Gene Transcription Regulation Database (GTRD). The tumor microenvironment was also evaluated based on the TCGA dataset. Results We found that Wilms tumor gene 1 (WT1), a transcription factor, was highly expressed and hypermethylated in all the four BC subtypes. All the WT1 methylation sites exhibited hypermethylation. The methylation levels of the TSS200 and 1stExon regions were negatively correlated with WT1 expression in two BC subtypes, while that of the gene body region was positively associated with WT1 expression in three BC subtypes. Patients with low WT1 expression had better overall survival (OS). Five genes including COL11A1, GFAP, FGF5, CD300LG, and IGFL2 were predicted as the downstream genes of WT1. Those five genes were dysregulated in the four BC subtypes. Patients with a favorable 6-gene signature (low expression of WT1 and its five predicted downstream genes) exhibited better OS than that with an unfavorable 6-gene signature. We also found a correlation between WT1 and tamoxifen using STITCH. Higher infiltration rates of CD8 T cells, plasma cells, and monocytes were found in the lower quartile WT1 group and the favorable 6-gene signature group. In conclusion, we demonstrated that WT1 is hypermethylated and up-regulated in the four BC molecular subtypes and a 6-gene signature may predict BC prognosis.

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Section: Discussionsupporting

confidence: 94%

Comprehensive analysis based on DNA methylation and RNA-seq reveals hypermethylation of the up-regulated WT1 gene with potential mechanisms in PAM50 subtypes of breast cancer

Ren

Tang

Lan

2021

PeerJ

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“…As these findings align with the sequencing data obtained in our study, its expression level in GC is yet to be clarified. Through a study of ADAMTS1 in breast cancer, its expression level was found to be low [ 18 – 21 ]. However, another study found that it can promote breast cancer metastasis [ 22 ].…”

Section: Discussionmentioning

confidence: 99%

Prognostic Values for the mRNA Expression of the ADAMTS Family of Genes in Gastric Cancer

Liang

Zhu

Chen

et al. 2020

Journal of Oncology

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The “A Disintegrin and Metalloproteinase with Thrombospondin Motif” (ADAMTS) family of genes is involved in the occurrence and development of different cancers. However, the prognostic value of these genes in gastric cancer (GC) has not been revealed. The present study was thus conducted to determine the prognostic value for the ADAMTS family of genes in GC. First, we evaluated the mRNA expression levels of the ADAMTS family in GC patients using a GEPIA dataset. Thereafter, we determined the prognostic value of these genes by analyzing their mRNA level using the Kaplan–Meier Plotter database. The mRNA expression level of ADAMTS12 was randomly validated by qRT-PCR and meta-analysis while its coexpression genes were derived using Coexpedia. Finally, we performed Gene Ontology (GO) annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses using the OmicShare Tools. Compared to normal tissues, expression of ADAMTS2 and 12 was significantly higher while that of ADAMTS1, 13, and 15 was significantly lower in GC tissues. According to the RNA-seq and gene chip data, the ADAMTS family (6, 7, 12, 15, and 18) of genes was closely related to the prognosis of GC, and their high expression levels were associated with poor prognosis and survival time. In addition, ADAMTS12 was highly expressed in 20 pairs of GC tissues based on RT-PCR (P=0.016) and meta-analysis (SMD: 0.73, 95% CI: 0.32–1.14, P<0.001). GO and KEGG pathway analyses indicated that the ADAMTS12 coexpressed genes were enriched in the pathways of extracellular matrix organization, extracellular matrix structural constituent, extracellular matrix, and protein digestion and absorption. Herein, we discovered the prognostic values and biological roles of the ADAMTS genes in GC.

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“…In depth, we explored HDAC2's potential target that might be involved in ARAP1-AS1-regulated BC development. And PLIN1, a recently identified anti-tumor gene in BC [23,24] was chosen to be research object since UCSC suggested that HDAC2 might be one of potential regulators of it. First of all, we uncovered that inhibition of HDAC2 gave rise to the mRNA and protein expressions of PLIN1 in both MCF7 and MDA-MB-231 cells ( Figure 3A,B).…”

Section: Plin1 Is Negatively Regulated By Hdac2 At Transcriptional Levelmentioning

confidence: 99%

Long non-coding RNA ARAP1-AS1 accelerates cell proliferation and migration in breast cancer through miR-2110/HDAC2/PLIN1 axis

Wang

Zhao

et al. 2020

Bioscience Reports

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Breast cancer (BC) poses a great threaten to women health. Numerous evidences suggest the important role of long non-coding RNAs (lncRNAs) in BC development. In the present study, we intended to investigate the role of ARAP1-AS1 in BC progression. First of all, the GEPIA data suggested that ARAP1-AS1 was highly expressed in breast invasive carcinoma (BRAC) tissues compared with the normal breast tissues. Meanwhile, the expression of ARAP1-AS1 was greatly up-regulated in BC cell lines. ARAP1-AS1 knockdown led to repressed proliferation, strengthened apoptosis and blocked migration of BC cells. Moreover, ARAP1-AS1 could boost HDAC2 expression in BC through sponging miR-2110 via a ceRNA mechanism. Of note, the UCSC predicted that HDAC2 was a potential transcriptional regulator of PLIN1, an identified tumor suppressor in BC progression. Moreover, we explained that the repression of HDAC2 on PLIN1 was owing to its deacetylation on PLIN1 promoter. More importantly, depletion of PLIN1 attenuated the mitigation function of ARAP1-AS1 silence on the malignant phenotypes of BC cells. To sum up, ARAP1-AS1 serves a tumor-promoter in BC development through modulating miR-2110/HDAC2/PLIN1 axis, which may help to develop novel effective targets for BC treatment.

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Study of Gene Expression Profiles of Breast Cancers in Indian Women

Cited by 39 publications

References 103 publications

Comprehensive analysis based on DNA methylation and RNA-seq reveals hypermethylation of the up-regulated WT1 gene with potential mechanisms in PAM50 subtypes of breast cancer

Comprehensive analysis based on DNA methylation and RNA-seq reveals hypermethylation of the up-regulated WT1 gene with potential mechanisms in PAM50 subtypes of breast cancer

Prognostic Values for the mRNA Expression of the ADAMTS Family of Genes in Gastric Cancer

Long non-coding RNA ARAP1-AS1 accelerates cell proliferation and migration in breast cancer through miR-2110/HDAC2/PLIN1 axis

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