PAX8 is a potential marker for the diagnosis of primary epithelial ovarian cancer

Chai, Hongjuan; Ren, Qing; Fan, Qin; Liu, Ye; Du, Guangye; Du, Hua‐Wen; Xu, Wei; Li, Yue; Zhang, Lan; Cheng, Zhongping

doi:10.3892/ol.2017.6949

Cited by 26 publications

(26 citation statements)

References 23 publications

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“…PAX8 is also a promising prognostic marker for ovarian cancer with a threshold of 3+ staining in ≥51% cells. 64 Although the percentage decrease in H-score during the DTF time course was not significant, we observed a reduction in the percentage of 3+ PAX8-stained cells in ovary specimens. Furthermore, although different immunoscoring schemes preclude direct comparisons, the reduction in proportion of 3+ WT1 immunopositive cells we observed after a DTF ≥2 hr may straddle the eligibility criteria (an immunoreactive score [IRS] score of 4-12) for a phase I clinical trial on a WT1 vaccine to prevent ovarian cancer reoccurrence (NCT02737787).…”

Section: Discussioncontrasting

confidence: 61%

Impact of Preanalytical Factors on the Measurement of Tumor Tissue Biomarkers Using Immunohistochemistry

Bagchi

Madaj

Engel³

et al. 2021

J Histochem Cytochem.

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Analysis of formalin-fixed paraffin-embedded (FFPE) tissue by immunohistochemistry (IHC) is commonplace in clinical and research laboratories. However, reports suggest that IHC results can be compromised by biospecimen preanalytical factors. The National Cancer Institute’s Biospecimen Preanalytical Variables Program conducted a systematic study to examine the potential effects of delay to fixation (DTF) and time in fixative (TIF) on IHC using 24 cancer biomarkers. Differences in IHC staining, relative to controls with a DTF of 1 hr, were observed in FFPE kidney tumor specimens after a DTF of ≥2 hr. Reductions in H-score and/or staining intensity were observed for c-MET, p53, PAX2, PAX8, pAKT, and survivin, whereas increases were observed for RCC1, EGFR, and CD10. Prolonged TIF of 72 hr resulted in significantly reduced H-scores of CD44 and c-Met in kidney tumor specimens, compared with controls with 12-hr TIF. An elevated probability of altered staining intensity due to DTF was observed for nine antigens, whereas for prolonged TIF an elevated probability was observed for one antigen. Results reported here and elsewhere across tumor types and antigens support limiting DTF to ≤1 hr when possible and fixing tissues in formalin for 12–24 hr to avoid confounding effects of these preanalytical factors on IHC.

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Section: Discussioncontrasting

confidence: 61%

Impact of Preanalytical Factors on the Measurement of Tumor Tissue Biomarkers Using Immunohistochemistry

Bagchi

Madaj

Engel³

et al. 2021

J Histochem Cytochem.

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“…PAX8 (a member of paired box PAX gene family) is a positive marker of FTSECs 89 and is elevated in a variety of tumors 90 – 95 . Our prior findings demonstrated that PAX8 was upregulated following chronic iron exposure 10 ; we now validate this observation and further show that it is epigenetically regulated, also supported by prior literature 59 .…”

Section: Resultsmentioning

confidence: 99%

Global miRNA/proteomic analyses identify miRNAs at 14q32 and 3p21, which contribute to features of chronic iron-exposed fallopian tube epithelial cells

Chhabra

Rockfield

Guergues

et al. 2021

Sci Rep

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Malignant transformation of fallopian tube secretory epithelial cells (FTSECs) is a key contributing event to the development of high-grade serous ovarian carcinoma (HGSOC). Our recent findings implicate oncogenic transformative events in chronic iron-exposed FTSECs, including increased expression of oncogenic mediators, increased telomerase transcripts, and increased growth/migratory potential. Herein, we extend these studies by implementing an integrated transcriptomic and mass spectrometry-based proteomics approach to identify global miRNA and protein alterations, for which we also investigate a subset of these targets to iron-induced functional alterations. Proteomic analysis identified > 4500 proteins, of which 243 targets were differentially expressed. Sixty-five differentially expressed miRNAs were identified, of which 35 were associated with the “top” proteomic molecules (> fourfold change) identified by Ingenuity Pathway Analysis. Twenty of these 35 miRNAs are at the 14q32 locus (encoding a cluster of 54 miRNAs) with potential to be regulated by DNA methylation and histone deacetylation. At 14q32, miR-432-5p and miR-127-3p were ~ 100-fold downregulated whereas miR-138-5p was 16-fold downregulated at 3p21 in chronic iron-exposed FTSECs. Combinatorial treatment with methyltransferase and deacetylation inhibitors reversed expression of these miRNAs, suggesting chronic iron exposure alters miRNA expression via epigenetic alterations. In addition, PAX8, an important target in HGSOC and a potential miRNA target (from IPA) was epigenetically deregulated in iron-exposed FTSECs. However, both PAX8 and ALDH1A2 (another IPA-predicted target) were experimentally identified to be independently regulated by these miRNAs although TERT RNA was partially regulated by miR-138-5p. Interestingly, overexpression of miR-432-5p diminished cell numbers induced by long-term iron exposure in FTSECs. Collectively, our global profiling approaches uncovered patterns of miRNA and proteomic alterations that may be regulated by genome-wide epigenetic alterations and contribute to functional alterations induced by chronic iron exposure in FTSECs. This study may provide a platform to identify future biomarkers for early ovarian cancer detection and new targets for therapy.

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“…PAX8 is a biomarker for diagnosis of several types of malignant tumors [19,20]. To understand the potential role of PAX8 in the progression of HCC, the expression of PAX8 in HCC and nontumor liver tissues in the Oncomine and TCGA was analyzed.…”

Section: Pax8 Silencing Inhibits the Growth Of Hcc In Vitro And In Vivomentioning

confidence: 99%

HBx regulates transcription factor PAX8 stabilization to promote the progression of hepatocellular carcinoma

Wang

Huang

et al. 2019

Oncogene

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Transcription factor PAX8 expression is upregulated in several types of cancers. However, little is known about the function of PAX8 in the progression of hepatoma and its regulatory mechanisms. Here, we show that PAX8 silencing inhibits the proliferation and clonogenicity of hepatoma cells and its growth in vivo. The HBV X protein (HBx) does not directly interacts, but stabilizes PAX8 by inhibiting proteasome-dependent ubiquitination and degradation. Furthermore, the E3 ubiquitin ligase complex component Skp2 through its LRR domain directly interacts with the Prd domain of PAX8 and targets PAX8 by recognizing its lysine 275 for ubiquitination and degradation in hepatoma cells. In addition, HBx directly interacts and is colocalized with Skp2 to inhibit its recognition and subsequent ubiquitination and degradation of PAX8 in hepatoma cells. Moreover, HBx upregulates the expression and phosphorylation of Aurora A, a serine-threonine kinase, which interacts with and phosphorylates PAX8 at S209 and T277, compromising the Skp2-recognized PAX8 ubiquitination and destabilization. Thus, HBx stabilizes PAX8 protein by inhibiting the Skp2 targeted PAX8 ubiquitination and enhancing the Aurora A-mediated its phosphorylation, contributing to the progression of hepatoma. Our findings suggest that PAX8 may a new target for design of therapies and uncover new insights into the pathogenesis of hepatoma.

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PAX8 is a potential marker for the diagnosis of primary epithelial ovarian cancer

Cited by 26 publications

References 23 publications

Impact of Preanalytical Factors on the Measurement of Tumor Tissue Biomarkers Using Immunohistochemistry

Impact of Preanalytical Factors on the Measurement of Tumor Tissue Biomarkers Using Immunohistochemistry

Global miRNA/proteomic analyses identify miRNAs at 14q32 and 3p21, which contribute to features of chronic iron-exposed fallopian tube epithelial cells

HBx regulates transcription factor PAX8 stabilization to promote the progression of hepatocellular carcinoma

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