AXIN1 Expression and Localization in Meningiomas and Association to Changes of APC and E-cadherin

Pećina‐Šlaus, Nives; Kafka, Anja; Vladušić, Tomislav; Pećina, Hrvoje Ivan; Hrašćan, Reno

doi:10.21873/anticanres.11007

Cited by 10 publications

(6 citation statements)

References 48 publications

(64 reference statements)

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“…8,[51][52][53][54][55][56] These studies concentrated on mutational analyses, proteomics, and so on, but did not search for MSI of Wnt signaling genes. In our previous work, we came across MSI for AXIN1 and CDH1 that in our opinion could not be neglected 57 and decided to explore this line of evidence on a larger group of meningiomas. Consequently, in this study, we found a higher percent of MSI for AXIN1 gene (17.8%), while CDH1 displayed similar frequency (8.3%).…”

Section: Discussionmentioning

confidence: 99%

Genetic changes of MLH1 and MSH2 genes could explain constant findings on microsatellite instability in intracranial meningioma

et al. 2017

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Postreplicative mismatch repair safeguards the stability of our genome. The defects in its functioning will give rise to microsatellite instability. In this study, 50 meningiomas were investigated for microsatellite instability. Two major mismatch repair genes, MLH1 and MSH2, were analyzed using microsatellite markers D1S1611 and BAT26 amplified by polymerase chain reaction and visualized by gel electrophoresis on high-resolution gels. Furthermore, genes DVL3 (D3S1262), AXIN1 (D16S3399), and CDH1 (D16S752) were also investigated for microsatellite instability. Our study revealed constant presence of microsatellite instability in meningioma patients when compared to their autologous blood DNA. Altogether 38% of meningiomas showed microsatellite instability at one microsatellite locus, 16% on two, and 13.3% on three loci. The percent of detected microsatellite instability for MSH2 gene was 14%, and for MLH1, it was 26%, for DVL3 22.9%, for AXIN1 17.8%, and for CDH1 8.3%. Since markers also allowed for the detection of loss of heterozygosity, gross deletions of MLH1 gene were found in 24% of meningiomas. Genetic changes between MLH1 and MSH2 were significantly positively correlated (p = 0.032). We also noted a positive correlation between genetic changes of MSH2 and DVL3 genes (p = 0.034). No significant associations were observed when MLH1 or MSH2 was tested against specific histopathological meningioma subtype or World Health Organization grade. However, genetic changes in DVL3 were strongly associated with anaplastic histology of meningioma (χ = 9.14; p = 0.01). Our study contributes to better understanding of the genetic profile of human intracranial meningiomas and suggests that meningiomas harbor defective cellular DNA mismatch repair mechanisms.

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Section: Discussionmentioning

confidence: 99%

Genetic changes of MLH1 and MSH2 genes could explain constant findings on microsatellite instability in intracranial meningioma

et al. 2017

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“…Nevertheless, seven out of 32 samples (21.9%) demonstrated negative or very weak AXIN1 expression levels with exclusive cytoplasmic localization when compared to the levels of AXIN1 in healthy brain tissues. Strong statistical correlations were observed between cytoplasmic localization of AXIN1 and its weak expression; and also between the simultaneous cytoplasmic and nuclear localizations; and moderate and strong expression levels ( p < 0.000) [ 109 ].…”

Section: Key Wnt Signalling Molecules Involved In Meningiomamentioning

confidence: 99%

Molecular Genetics of Intracranial Meningiomas with Emphasis on Canonical Wnt Signalling

Pećina‐Šlaus

Kafka

Lechpammer

2016

Cancers

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Research over the last decade recognized the importance of novel molecular pathways in pathogenesis of intracranial meningiomas. In this review, we focus on human brain tumours meningiomas and the involvement of Wnt signalling pathway genes and proteins in this common brain tumour, describing their known functional effects. Meningiomas originate from the meningeal layers of the brain and the spinal cord. Most meningiomas have benign clinical behaviour and are classified as grade I by World Health Organization (WHO). However, up to 20% histologically classified as atypical (grade II) or anaplastic (grade III) are associated with higher recurrent rate and have overall less favourable clinical outcome. Recently, there is emerging evidence that multiple signalling pathways including Wnt pathway contribute to the formation and growth of meningiomas. In the review we present the synopsis on meningioma histopathology and genetics and discuss our research regarding Wnt in meningioma. Epithelial-to-mesenchymal transition, a process in which Wnt signalling plays an important role, is shortly discussed.

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“…We did not find any alterations in AXIN1 mRNA expression between AP and HP compared with normal control samples, which is in contrast to previous studies regarding reduction of AXIN1 in malignant behavior of lung cancers, meningeal brain tumors, oral squamous cell carcinoma carcinogenesis, metastasis, and esophageal squamous cell carcinoma. [39][40][41][42][43] It may be concluded that this gene is ineffective during early steps of the changes in the colon tissue and CRC initiation, while other studies mentioned above focused on the expression of this target gene after tumor formation and metastasis.…”

Section: Discussionmentioning

confidence: 99%

APC and AXIN2 Are Promising Biomarker Candidates for the Early Detection of Adenomas and Hyperplastic Polyps

et al. 2020

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Aberrant activation of the WNT/CTNNB1 pathway is notorious in colorectal cancer (CRC). Here, we demonstrate that the expression of specific and crucial WNT signaling pathway genes is linked to disease progression in colonic adenomatous (AP) and hyperplastic (HP) polyps in an Iranian patient population. Thus, we highlight potential gene expression profiles as candidate novel biomarkers for the early detection of CRC. From a 12-month study (2016-2017), 44 biopsy samples were collected during colonoscopy from the patients with colorectal polyps and 10 healthy subjects for normalization. Clinical and demographic data were collected in all cases, and mRNA expression of APC, CTNNB1, CDH1, AXIN1, and AXIN2 genes was investigated using real-time polymerase chain reaction (PCR). CTNNB1 and CDH1 expression levels were unaltered in AP and HP subjects, whereas mRNA expression of APC was decreased in AP contrasted with HP subjects, with a significant association between APC downregulation and polyp size. Although AXIN1 showed no changes between AP and HP groups, a significant association between AXIN1 and dysplasia grade was found. Also, significant upregulation of AXIN2 in both AP and HP subjects was detected. In summary, we have shown increased expression of AXIN2 and decreased expression of APC correlating with grade of dysplasia and polyp size. Hence, AXIN2 and APC should be explored as biomarker candidates for early detection of AP and HP polyps in CRC.

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AXIN1 Expression and Localization in Meningiomas and Association to Changes of APC and E-cadherin

Abstract: Our findings on genetic changes and expression levels of AXIN1 bring novel data on its involvement in meningeal brain tumors and reveal AXIN1's relation to specific Wnt molecules.

Cited by 10 publications

References 48 publications

Genetic changes of MLH1 and MSH2 genes could explain constant findings on microsatellite instability in intracranial meningioma

Genetic changes of MLH1 and MSH2 genes could explain constant findings on microsatellite instability in intracranial meningioma

Molecular Genetics of Intracranial Meningiomas with Emphasis on Canonical Wnt Signalling

APC and AXIN2 Are Promising Biomarker Candidates for the Early Detection of Adenomas and Hyperplastic Polyps

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