Identification of differentially expressed microRNAs as potential biomarkers for carcinoma ex pleomorphic adenoma
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE205670 | GEO | 2022/06/13
REPOSITORIES: GEO
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Project description:BACKGROUND: potential epigenetic biomarkers for malignant transformation to carcinoma ex pleomorphic adenoma (Ca ex PSA) have been sought previously with and without specific comparison with the benign variant, pleomorphic salivary adenoma (PSA). Previous analysis has been limited by a non-quantitative approach. We sought to demonstrate quantitative promoter methylation across a panel of tumour suppressor genes (TSGs) in both Ca ex PSA and PSA. METHODS: quantitative methylation-specific real-time polymerase chain reaction (qMSP) analysis of p16(INK4A), CYGB, RASSF1, RAR?, human telomerase reverse transcriptase (hTERT), Wilms' tumour 1 (WT1) and TMEFF2 gene promoters was undertaken on bisulphite-converted DNA, previously extracted from archival fixed tissue specimens of 31 Ca ex PSA and an unrelated cohort of 28 PSA. All target regions examined had formerly been shown to be hypermethylated in salivary and/or mucosal head and neck malignancies. RESULTS: the qMSP demonstrated abnormal methylation of at least one target in 20 out of 31 (64.5%) Ca ex PSA and 2 out of 28 (7.1%) PSA samples (P<0.001). RASSF1 was the single gene promoter for which methylation is shown to be a statistically significant predictor of malignant disease (P<0.001) with a sensitivity of 51.6% and a specificity of 92.9%. RAR?, TMEFF2 and CYGB displayed no apparent methylation, while a combinatory epigenotype based on p16, hTERT, RASSF1 and WT1 was associated with a significantly higher chance of detecting malignancy in any positive sample (odds ratio: 24, 95% CI: 4.7-125, P<0.001). CONCLUSIONS: we demonstrate the successful application of qMSP to a large series of historical Ca ex PSA samples and report on a panel of TSGs with significant differences in their methylation profiles between benign and malignant variants of pleomorphic salivary adenoma. qMSP analysis could be developed as a useful clinical tool to differentiate between Ca ex PSA and its benign precursor.
| S-EPMC3008600 | biostudies-literature
Project description:We identified transcriptional landscape in pleomorphic adenoma (PA).
2024-07-14 | GSE180105 | GEO
Project description:Identification of differentially expressed microRNAs as potential biomarkers for carcinoma ex pleomorphic adenoma
| PRJNA847079 | ENA
Project description:Salivary duct carcinoma (SDC) is morphologically similar to breast cancer, with HER2-overexpression reported. With regard to the pattern of disease onset, SDC can arise from de novo or carcinoma ex-pleomorphic adenoma (Ca-ex-PA). Recently, multiple molecular profiles of SDC as well as breast cancer have been reported, with significant differences in HER2 expression between Ca-ex-PA and de novo. We assessed the differences in gene expression between onset classifications. We conducted immunohistochemical analysis and HER2-DISH for 23 patients and classified SDCs into three subtypes as follows: "HER2-positive" (HER2+/any AR), "Luminal-AR" (HER2-/AR+), and "Basal-like" (HER2-/AR-). We assessed the expression levels of 84 functional genes for 19 patients by using a qRT-PCR array. Ten cases were classified as HER2-positive, seven cases as Luminal-AR, and six cases as Basal-like. The gene expression pattern was generally consistent with the corresponding immunostaining classification. The expression levels of VEGFA, ERBB2(HER2), IGF1R, RB1, and XBP1 were higher, while those of SLIT2 and PTEN were lower in Ca-ex-PA than in de novo. The functions of those genes were concentrated in angiogenesis and AKT/PI3K signaling pathway (Fisher's test: p-value = 0.025 and 0.004, respectively). Multiple machine learning methods, OPLS-DA, LASSO, and RandomForest, also show that VEGFA can be a candidate for the characteristic differences between Ca-ex-PA and de novo. In conclusion, the AKT/PI3K signaling pathway leading to angiogenesis was hyper-activated in all SDCs, particularly in those classified into the Ca-ex-PAs. VEGFA was over-expressed significantly in the Ca-ex-PA, which can be a crucial factor in the malignant conversion to SDC.
| S-EPMC7937931 | biostudies-literature
Project description:Incomplete excision of pleomorphic adenoma (PA) may result in recurrent pleomorphic adenoma (RPA). Furthermore, long-term neglected PA may become carcinoma ex pleomorphic adenoma (CXPA). In the present study, the relationships between mast cell-derived chymase and these tumors were examined. The tumor tissues of PA consisted of either or both glandular and fibrotic structures. Histological features of RPA were almost similar to those of PA, except that they showed multinodular structures. CXPA is composed of a mixture of PA and carcinoma. The main stromal cells in PA were myofibroblasts, whereas fibroblasts constituted the main cellular portion in the stromal tissue of RPA. Cancer-associated fibroblasts (CAFs) were present abundantly in CXPA. With increased VEGF expression, neovascularization tended to increase in RPA or CXPA. Compared with PA, chymase-positive mast cells, as well as chymase gene expression, were increased in the tumor tissues from patients with RPA or CXPA. SCF, TGFβ1, and PCNA-positive staining was widely observed in these tumor tissues. The above results suggest that mast cell-derived chymase through its direct or cooperative effects with other mediators may participate in the pathophysiology of RPA and CXPA.
| S-EPMC8657626 | biostudies-literature
Project description:Invasive malignant pleomorphic adenoma (IMPA) results from the malignant transformation of pleomorphic adenoma (PA). The former is a high-grade malignant tumor, whereas the latter is a benign opposite. Study on the molecular mechanism in the progression of PA to IMPA will be of benefit to elucidate the reasons for different biological behaviors among these salivary gland tumors with the same origin. But there is no valuable and non-invasive biomarker to screen IMPA currently. Studies showed many salivary molecules can detect several systemic diseases. We aimed to investigate whether salivary mRNAs (mRNA) can act as a biomarker to detect IMPA.
2022-01-12 | GSE179895 | GEO
Project description:The most common benign salivary tumour is a pleomorphic adenoma. Transformation to malignancy, carcinoma ex pleomorphic adenoma (cxpa), occurs in 6% of cases. Management focuses on surgical resection and radiotherapy; however, rare cases require systemic management. We present the case of a 60-year-old woman with a cxpa of the left parotid gland who required systemic therapy for locally recurrent disease. Treatment options were guided by the literature concerning malignant salivary gland tumour and by whole-genome and transcriptome sequencing of the tumour. The patient received multiple systemic agents during the course of her disease, with cyclophosphamide-doxorubicin-cisplatin providing the best control (partial response). Genomeand transcriptome-directed therapy, including sorafenib and vismodegib, were utilized with limited clinical benefit. Malignant transformation in cxpa is a complex process, and therapy directed at a single tumour pathway might not be sufficient to control disease.
| S-EPMC5486399 | biostudies-literature
Project description:The presence of melanin pigment and melanocytic markers expression have been rarely reported in salivary gland tumors. Herein, two cases of carcinoma arising in pleomorphic adenoma of the parotid gland and showing diffuse expression of myoepithelial and melanocytic markers are described. The clinical-pathological clues useful in the differential diagnosis with melanoma are discussed. In addition, a review of the pertinent literature is also proposed, discussing the pathologic mechanisms potentially involved in this phenomenon.
| S-EPMC8633150 | biostudies-literature
Project description:We report a case of carcinoma ex pleomorphic adenoma of a sublingual gland in a 70-year-old man. Under a clinical diagnosis of benign salivary gland tumor, excision of the mass with the sublingual salivary gland in an en bloc fashion via an intraoral approach was performed. Histopathologically, there was a rupture of the fibrous capsule and diffuse cell-rich sheets composed of myoepithelial cells with round nuclei were also seen. Immunohistochemically, the cells that composed of cell rich sheets were positive to smooth muscle actin. Final diagnosis of myoepithelial carcinoma ex pleomorphic adenoma was made.
| S-EPMC3421480 | biostudies-other
Project description:OBJECTIVES:For lesions in the salivary glands, ultrasonography (US) is an ideal tool for initial assessment. The aim of this study was to characterize and differentiate between the Gray scale and Doppler US findings of intracapsular carcinoma ex pleomorphic adenoma (Ic-CxPA) and invasive carcinoma ex pleomorphic adenoma (Inv-CxPA). METHODS:A total of 87 patients (89 lesions) with histopathologically proven CxPA underwent US examination. The following characteristics were assessed on US images: size, shape, border, echogenicity, echo texture, posterior echo, vascularity, and regional lymph node enlargement. One-way analysis of variance (ANOVA), nonparametric test, Fisher's exact test, chi-square test and receiver operating characteristic (ROC) curve were used for the analyses of the US findings of Ic-CxPAs and Inv-CxPAs. RESULTS:We found that on US images, nearly all Ic-CxPAs (10/11) and a few of Inv-CxPAs (17/78) showed benign features, such as a regular shape, a well-defined border, and enhancement of posterior echo, while most Inv-CxPAs (61/78) showed one or more following features: an irregular shape, an ill-defined border, and lack of enhancement of posterior echo. CONCLUSIONS:Ic-CxPAs tended to exhibit benign features, whereas most Inv-CxPAs tended to exhibit one or more invasive features. US can provide strong evidence in differentiating Inv-CxPAs from Ic-CxPAs.
| S-EPMC5991755 | biostudies-other