Liu Qian

Aberrant expression of the sFRP and WIF1 genes in invasive non-functioning pituitary adenomas

Non-functioning pituitary adenomas (NFPAs) are the most common pituitary tumors and mainly invade the sphenoid, cavernous sinus or dura mate. Aberrant regulation of the Wnt signaling pathway plays an important role in tumorigenesis. This study was designed to investigate the relationships between secreted frizzled-related proteins (sFRPs), WIF1 genes and the invasion of NFPAs by tissue microassays (TMAs) of samples from 163 patients. Significantly weaker staining of WIF1 and sFRP4 were detected in the invasive group compared with the non-invasive group by TMAs (pu202f=u202f0.002, pu202f<u202f0.001). Univariate analysis showed a significant correlation between tumor invasion and low expression of WIF1 and sFRP4 (pu202f=u202f0.002, pu202f<u202f0.001). A similar trend was observed when analyzing the mRNA and protein levels through RT-PCR and western blot experiments. Methylation of the WIF1 promoter was significantly increased in invasive NFPAs compared with the noninvasive group (pu202f=u202f0.004). The average progression free survival time in the high WIF1 group was longer than that in the low WIF1 group (pu202f=u202f0.025). Furthermore, RT-PCR measured the levels of 11 miRNAs targeting WIF1 according to the Targetscan database and PubMed. The levels of miRNA-137, miRNA-374a-5p and miRNA-374b-5p in the invasive group were 0.037-fold, 0.577-fold and 0.44-fold that of the noninvasive group (pu202f=u202f0.003, pu202f=u202f0.049 and pu202f=u202f0.047). Overexpression of miRNA-137 could inhibit the proliferation and invasion of GH3 cells through cell viability and Transwell experiments (pu202f<u202f0.05). Furthermore, the WIF1 level was upregulated after overexpression of miRNA-137 compared with miRNA-137-NC (control miRNA) in GH3 cells. Our data suggest that WIF1 may be potential biomarker for the aggressiveness of NFPAs. miRNA-137 plays an important role in the Wnt signaling pathway by affecting promoter methylation of WIF1.

The role of NR2C2 in the prolactinomas

Abstract Prolactinomas are the most frequently observed pituitary adenomas. Prolactinomas invasion is a key risk factor associated with operation results, and it is highly correlated with clinical prognosis. Nuclear receptor subfamily 2 group C member 2 (NR2C2) first cloned from testis is involved in the invasion and metastasis of several human tumors. In 46 patients with prolactinamas, the expression levels of CCNB1, Notch2, and NR2C2 was determined with tissue micro-array (TMA). The association between NR2C2 levels and clinical parameters was established with univariate analysis. The levels of Notch2 and CCNB1 were analyzed by RT-PCR and western blot techniques.The average methylation levels of the NR2C2 promoter were 0.505 and 0.825 in invasive prolactinomas (IPA) and non-IPA groups, respectively (p = 0.013). Univariate analysis also showed that there is a significant relationship between high NR2C2 expression and invasion (x2 = 7.043, p = 0.008), prolactin granules (x2 = 8.712, p = 0.003), and tumor size (x2 = 4.261, p = 0.039.) With the knockdown of NR2C2, cell proliferation was inhibited. Genes related to epithelial-mesenchymal transition (EMT) induced the apoptosis in MMQ cells. In addition, the level of Notch2 and CCNB1 were down-regulated with the knockdown of NR2C2. Moreover, miR-129-5p reduced mRNA levels of NR2C2, and they inhibited cell proliferation by inducing apoptosis levels of MMQ cells. Our findings proved NR2C2 played the important role in tumorigenesis tumor invasion of prolactinomas; moreover, NR2C2 is identified as a potential target.

Detection of circulating tumor cells in patients with pituitary tumors

BackgroundCirculating tumor cells (CTCs) are tumor cells that have shed from a primary tumor and circulate in the peripheral blood. Recent experimental and clinical studies show that CTCs can be detected in early-stage disease.Case presentationWe report three cases of pituitary adenoma (PA) in which tumor cells with particles were detected in the interstitial vascular compartment by transmission electron microscopy. Tumors were completely resected. Immunohistochemical analysis showed a β-catenin score of 10.5u2009±u20091.5 in the three cases with CTCs compared with 2.4u2009±u20090.5 in 24 control adenomas. The Ki-67 labeling index was 2.1u2009±u20090.7 in CTCs vs. 0.2u2009±u20090.3 in control cases (pu2009=u20090.043), and the p53 score was 4.33u2009±u20091.3 vs. 0.31u2009±u20090.17 (pu2009=u20090.000). The E-cadherin score did not differ significantly between the two groups.ConclusionsCTCs can be detected in benign tumors such as PAs and not only in late-stage malignant tumors with apparent distant metastases. The present findings suggest that pituitary carcinomas develop from adenomas.