PAX8 EXPRESSION AND ITS ASSOCIATIONS IN PRIMARY RENAL CELL CARCINOMA: A CROSS SECTIONAL STUDY

Objective: To determine the frequency of PAX8 expression in cases of primary renal cell carcinoma (RCC) and its association with patient demographics and tumor type. Study Design: Cross sectional study. Place and Duration of Study: Department of Histopathology, Armed Forces Institute of Pathology, Rawalpindi, from Jun 2016 to Jun 2017. Methodology: After ethics approval, 57 cases were selected by non probability consecutive sampling. Inclusion criteria was diagnosis of primary renal cell carcinoma of all histological types, in both genders, among adults aged >18 years. Exclusion criteria were poorly fixed specimens and metastatic renal cell carcinoma. The main outcome measure was PAX8 frequency in renal cell carcinoma. The secondary outcome measure was correlation of PAX8 expression with age, gender, tumor type and grade. Data was entered and analyzed on Statistical Package for the Social Sciences. Results: Out of 57 cases, majority were males 37, (64.9%). The mean age was 55.35 ± 12.60 years. Clear cell carcinoma was the most frequent histopathologic variant in 47 (81%) cases followed by papillary carcinoma in 6 (10.2%), chromophobe cell carcinoma 2 (3.5%), sarcomatoid renal carcinoma 1 (1.75%) and mucinous tubular and spindle cell carcinoma 1 (1.75%). PAX8 expression was positive in 52 (91.2%). No significant difference was found in the frequency of PAX8 expression across age (p=0.321), gender (p=1.00) and tumor type (p=1.00). There was significant difference seen across tumor grade p=0.03. Conclusion: PAX8 is an important additional diagnostic marker for renal cell carcinoma. It can be recommended for inclusion in immunohistochemical panel for diagnosis..............

Evaluation of PAX8 Expression Promotes the Proliferation of Stomach Cancer cells

Background PAX8 was not only a mitotic factor, but identified as a transcription factor involved in the prognosis of human tumor patients. Elucidating the function of PAX8 on the pathology of stomach cancer was meaningful. Results: PAX8 was found to be upregulated in primary stomach cancer tissue and the TCGA stomach cancer dataset. Interestingly, SOX13 and PAX8 showed consistent expression patterns, and the combined high PAX8 and SOX18 expression induced a worse prognosis of stomach cancer patients. SOX13 was further identified as a transcription factor of PAX8, and further affect Aurora B and Cyclin B1 expression, two cell cycle related factors of the downstream of PAX8, including. Furthermore, PAX8 depletion inducted G1-phase arrest and the decrease of EdU incorporation, cell viability and colony formation can be rescued by SOX13 overexpression. Conclusions: SOX13 participated in the elevated expression of PAX8, which promote the proliferation of stomach cancer cells. Therefore, SOX13 mediated PAX8 expression was recognized as a tumor-promoting role in stomach cancer.

Evaluation of PAX8 Expression Promotes the Proliferation of Stomach Cancer cells

Background: PAX8 was identified as a mitosis-related regulator involved in the pathogenesis of human tumors and an indicator of the prognosis for patients. However, the function of PAX8 -in stomach cancer have not been studied. Aim: This study was aimed to explore the expression pattern of PAX8 in stomach cancer, and investigate the effect of PAX8 on the proliferation of stomach cancer cells. Methods: PAX8 expression pattern in stomach cancer was investigated in the “TCGA” database and compared in cancer and adjacent tissues of 36 clinical samples, in which the co-expression of SOX13 and PAX8 was confirmed by qRT-PCR. Based on the clinical record and IHC staining results, the survival curve was also mapped. Western blotting and qRT-PCR was used to analyze the effect of SOX13 on PAX8 and its downstream effector Aurora B and Cyclin B1 expression in AGS and MGC803 cells-. ChIP and luciferase assay were performed to explore SOX13 locate on the promoter of PAX8. Furthermore, CCK8, clone formation, EdU incorporation assay, and flow cytometry were used to detect the proliferative ability of AGS and MGC803 cell lines stably silenced PAX8. Results: PAX8 and SOX13 were identified to be synchronously upregulated in primary stomach cancer tissues and the TCGA stomach cancer datasets, and combined high PAX8 and SOX13 expression induced- worse prognosis. Furthermore, SOX13 can mediate PAX8 and its targeted genes expression, including Aurora B and Cyclin B1, in AGS and MGC803-. Flow cytometry and EdU incorporation assays showed that silencing PAX8 can block the cell cycle of stomach cancer cell in G1 phase and SOX13 expression can rescue the arrested proliferative process induced by PAX8 silence in CCK8 and colony formation assays. Conclusion: SOX13 participated in the elevated expression of PAX8,which promote the proliferation of stomach cancer cells, and both SOX13 and PAX8 act as an oncogene- in stomach cancer.

Evaluation of PAX8 expression promotes the proliferation of stomach Cancer cells

Background PAX8 was not only a mitotic factor, but identified as a transcription factor involved in the prognosis of human tumor patients. Elucidating the function of PAX8 on the pathology of stomach cancer was meaningful. Results PAX8 was found to be upregulated in primary stomach cancer tissue and the TCGA stomach cancer dataset. Interestingly, SOX13 and PAX8 showed consistent expression patterns, and the combined high PAX8 and SOX18 expression induced a worse prognosis of stomach cancer patients. SOX13 was further identified as a transcription factor of PAX8, and further affect Aurora B and Cyclin B1 expression, two cell cycle related factors of the downstream of PAX8, including. Furthermore, PAX8 depletion inducted G1-phase arrest and the decrease of EdU incorporation, cell viability and colony formation can be rescued by SOX13 overexpression. Conclusions SOX13 participated in the elevated expression of PAX8, which promote the proliferation of stomach cancer cells. Therefore, SOX13 mediated PAX8 expression was recognized as a tumor-promoting role in stomach cancer.

PAX8 expressing epithelial cells are a cancer-prone source of clonal cyclical regeneration of endometrial epithelium

Humans and mice have cyclical regeneration of the endometrial epithelium. It is expected that such regeneration is ensured by tissue stem cells. However, their location remains debatable. A number of recent studies have suggested the presence of stem cells in the mouse endometrial epithelium. At the same time, it has been reported this tissue can be regenerated by stem cells of stromal/mesenchymal or bone marrow cell origin. Here we show that cells expressing transcription factor PAX8 are the main contributor to the homeostatic regeneration of endometrial epithelium. In the uterus, based on a single-cell transcriptome and immunostaining analyses, PAX8 expression is limited to the endometrial epithelium. According to lineage tracing, PAX8 positive (PAX8+) epithelial cells are responsible for long-term maintenance of the epithelium. Furthermore, multicolor tracing shows that individual glands are formed by clonal expansion of cells labeling both glandular and luminal epithelial components. Inactivation of tumor suppressor genes Trp53 and Rb1 in PAX8+ cells but not FOXJ1+ cells leads to formation of neoplasms with features of serous endometrial carcinoma, the most aggressive type of human endometrial malignancy. Taken together, our results show that a progeny of single PAX8+ cells represent the main source of cyclical regeneration of the endometrial epithelium. They also provide direct experimental genetic evidence for the key roles of the P53 and RB pathways in the pathogenesis of serous endometrial carcinoma, and suggest that PAX8+ cells represent the cell-of-origin of this neoplasm.