Abstract
BackgroundThe p38MAPK family of Mitogen Activated Protein Kinases are a group of signalling molecules involved in cell growth, survival, proliferation and differentiation. The widely studied p38α isoform is ubiquitously expressed and is implicated in a number of cancer pathologies, as are p38γ and p38δ. However, the mechanistic role of the isoform, p38β, remains fairly elusive. Recent studies suggest a possible role of p38β in both breast and endometrial cancer with research suggesting involvement in bone metastasis and cancer cell survival. Female tissue specific cancers such as breast, endometrial, uterine and ovary account for over 3,000,000 cancer related incidents annually; advancements in therapeutics and treatment however require a deeper understanding of the molecular aetiology associated with these diseases. This study provides an overview of the MAPK signalling molecule p38β (MAPK11) in female cancers using an in-silico approach.MethodsA detailed gene expression and methylation analysis was performed using datasets from cBioportal, CanSar and MEXPRESS. Breast, Uterine Endometrial, Cervical, Ovarian and Uterine Carcinosarcoma TCGA cancer datasets were used and analysed.ResultsData using cBioportal and CanSAR suggest that expression of p38β is lower in cancers: BRCA, UCEC, UCS, CESC and OV compared to normal tissue. Methylation data from SMART and MEXPRESS indicate significant probe level variation of CpG island methylation status of the gene MAPK11. Analysis of the genes’ two CpG islands shows that the gene was hypermethylated in the CpG1 with increased methylation seen in BRCA, CESC and UCEC cancer data sets with a slight increase of expression recorded in cancer samples. CpG2 exhibited hypomethylation with no significant difference between samples and high levels of expression. Further analysis from MEXPRESS revealed no significance between probe methylation and altered levels of expression. In addition, no difference in the expression of BRCA oestrogen/progesterone/HER2 status was seen.ConclusionThis data provides an overview of the expression of p38β in female tissue specific cancers, showing a decrease in expression of the gene in BRCA, UCEC, CESC, UCS and OV, increasing the understanding of p38β MAPK expression and offering insight for future in-vitro investigation and therapeutic application.
Highlights
The establishment of cancer as one of the leading causes of morbidity and mortality globally is widely accepted, yet the complexity of molecular processes that contribute to the development and progression of the numerous subsets of cancer continues to plague researchers
The PanCancer analysis of MAPK11 provides an overview of expression throughout the early and advanced stages of the disease as well as the genetic alterations of MAPK11 that contribute towards changes in expression
Unlike the other female cancers, MAPK11 expression in Ovarian cancer (OV) is primarily shown at the advanced stage of the disease which is often the stage of diagnosis due to the ambiguity of
Summary
The establishment of cancer as one of the leading causes of morbidity and mortality globally is widely accepted, yet the complexity of molecular processes that contribute to the development and progression of the numerous subsets of cancer continues to plague researchers. Recurrence and mortality rates are still troublesome Gynaecological cancers such as uterine and endometrial are often detected at early to mid-stages with treatment for female reproductive tissue cancers often involving surgical procedures such as complete or partial mastectomy (breast) or hysterectomy [5]. Notwithstanding the continued advancements in detection and treatments of cancer many of the molecular mechanisms implicated in the development, progression and resistance related recurrence of female reproductive tissue specific cancers require further investigation [8]. Female tissue specific cancers such as breast, endometrial, uterine and ovary account for over 3,000,000 cancer related incidents annually; advancements in therapeutics and treatment require a deeper understanding of the molecular aetiology associated with these diseases. This study provides an overview of the MAPK signalling molecule p38β (MAPK11) in female cancers using an in-silico approach
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