scholarly journals Clinical Significance of Myeloid Zinc Finger 1 Expression in the Progression of Gastric Tumourigenesis

2017 ◽  
Vol 44 (3) ◽  
pp. 1242-1250 ◽  
Author(s):  
Guo-Qiang Li ◽  
Qing He ◽  
Lang Yang ◽  
Shu-Bin Wang ◽  
De-Dong Yu ◽  
...  

Background/Aims: To investigate the clinical significance of myeloid zinc finger 1 (MZF1) expression in various gastric mucosal lesions including chronic superficial gastritis (CSG), chronic atrophic gastritis (CAG), intestinal metaplasia (IM), dysplasia (DYS) and gastric cancer (GC) in comparison with normal tissues and gastric cell lines. Methods: MZF1 protein expression was detected using immunohistochemical staining in 37 CSG, 88 CAG, 77 IM, 51 DYS, 165 GC and 8 normal tissue samples. Quantitative real-time PCR (qRT-PCR) and western blotting were used to detect the level of MZF1 in gastric cell lines, 15 normal tissues and 34 GC samples, as well as 2 groups of paired primary GC and adjacent normal samples. Results: Reduced MZF1 expression was detected in most GC cells and tissues. Among the gastric tissues consisting of various stages of lesions (normal, CSG, CAG, IM, DYS and GC), MZF1 protein expression was downregulated in precancerous lesions and GC. The data from clinical analyses showed that decreased MZF1 expression was correlated with tumour invasion (p = 0.044), lymph node metastasis (p = 0.048) and poor prognosis of GC patients (p = 0.003). Moreover, MZF1 was identified as an independent prognostic biomarker for GC patients in multivariate Cox regression analysis (p = 0.009). Conclusion: Downregulation of MZF1 was associated with gastric tumourigenesis, which may be a novel early predictive and prognostic biomarker in GC patients.

2018 ◽  
Vol 49 (3) ◽  
pp. 1048-1059
Author(s):  
Ying Liu ◽  
Cheng Hu ◽  
Wen-Bo Zhu ◽  
Wen-Xiong Xu ◽  
Zhan-Yi Li ◽  
...  

Background/Aims: Zinc finger antiviral protein (ZAP) has been reported to be expressed in hepatocellular carcinoma (HCC), and ZAP expression is associated with apoptotic signaling in cancer cells. This study aimed at investigating the expression of ZAP in HCC cells and its significance in clinical pathology. Methods: Real-time quantitative PCR and western blot assays were employed to detect ZAP RNA and protein expression in normal human hepatocytes, HCC cells, and five primary HCC cell lines. Immunohistochemistry was performed to detect ZAP expression in 147 paraffin-embedded HCC tissues and adjacent normal tissues. The clinical significance of ZAP expression was analyzed in tissue samples from patients with or without infection by hepatitis B virus (HBV). Results: ZAP expression in HCC cells and human primary HCC cell lines was significantly lower than that of normal human hepatocytes. Among 147 HCC samples, ZAP expression was lower in HCC tissues than in adjacent normal tissues for 107 (77.0%) samples. In patients with HCC and HBV infection, ZAP expression was related to pathological grade (P < 0.05); in HBV-negative patients with HCC, ZAP expression was associated with tumor size (P < 0.05) and clinical stage (P < 0.05). The overall survival time in patients with low ZAP expression was significantly shorter than survival times of those with high ZAP expression (P < 0.05), especially for patients with moderately to well-differentiated HCC (Grade 1–2) and HCC at stage T1 and T2 (P < 0.05). Cox multivariate analysis showed that ZAP expression was an independent predictor of survival of patients with HCC (P < 0.01). Conclusion: Low ZAP expression is closely associated with disease progression and poor prognosis for patients with HCC.


2019 ◽  
Vol 17 ◽  
pp. 205873921982823
Author(s):  
Yuelou Yang ◽  
Xiangjun Jiang ◽  
Dong Li ◽  
Feiyan Wang ◽  
Qun Yang ◽  
...  

To investigate the correlation and clinical significance between programmed cell death factor 4 (PDCD4) and epidermal growth factor receptor 2 (Her-2) expressions and clinicopathological parameters in patients with gastric cancer, a total of 65 cases of gastric cancer and the corresponding normal mucosa with PDCD4 and Her-2 protein expressions were detected by SP immunohistochemical staining, and 50 cases of gastric cancer and the corresponding normal mucosa with PDCD4 and Her-2 protein expression quantities were detected by Western blot, in order to analyze the relationship between the positive expressions of PDCD4 and Her-2 protein and the clinicopathological features of patients with gastric cancer. The results showed that the positive rate of PDCD4 protein expression in gastric cancer tissues was 7.7%, which was significantly lower than that in the corresponding normal tissues, that is, 77.5% ( P < 0.05); the positive rate of Her-2 expression was 41.5%, which was significantly higher than that of the corresponding normal tissues, which is 2.5% ( P < 0.05). The Western blot test showed that the expression of PDCD4 protein in gastric cancer was 0.3105 ± 0.0073, which was significantly lower than that in the corresponding normal tissues, that is, 0.9428 ± 0.0127 ( P < 0.05); the expression level of Her-2 protein in gastric cancer tissues was 0.9428 ± 0.0127, which was significantly higher than that of the corresponding normal mucosa, which is 0.2054 ± 0.0264 ( P < 0.05). The positive expressions of PDCD4 (5/65) and Her-2 (27/65) were significantly correlated with the differentiation degrees and TNM stages of gastric cancer ( P < 0.05). However, no significant correlation can be observed from Table 2 ( P > 0.05), regarding sex, age, tumor size, and lymph node metastasis. Our research claimed that PDCD4 and Her-2 may play an important role in the invasion and metastasis of gastric cancer, which has a negative correlation with biological behaviors of gastric cancer. The low expression of PDCD4 and the high expression of Her-2 in gastric cancer may promote the occurrence and progression of cancer. The PDCD4 and Her-2 test can be used as an index to evaluate the malignant biological behaviors of gastric cancer and prognosis, and provide a theoretical basis for targeted therapy.


2019 ◽  
Vol 14 (1) ◽  
Author(s):  
Xin Shi ◽  
Xingfa Guan

Abstract Background Osteosarcoma (OS) is a malignancy predominantly occurred in children and adolescents. Numerous microRNAs are involved in the pathogenesis of various cancers. This study aimed to investigate the expression profiles of miR-99b and its prognostic value in OS patients, and further analyze the biological function of miR-99b in the tumor progression by using OS cells. Methods Expression of miR-99b was measured using quantitative real-time PCR. Kaplan-Meier survival curves and Cox regression analysis were performed to evaluate the prognostic value of miR-99b. OS cell lines were used to investigate the effects of miR-99b on cell proliferation, migration and invasion. Results A significant decreased expression of miR-99b was observed in the OS tissues and cell lines respectively compared with the normal tissues and cells. Aberrant expression of miR-99b was associated with the patients’ metastasis and TNM stage, and could be used to predict the prognosis of OS. The expression of miR-99b was regulated in vitro by cell transfection, and we found that the overexpression of miR-99b led to suppressed cell proliferation, migration and invasion, whereas the knockdown of miR-99b resulted in the opposite results. Conclusions In one word, the aberrantly expressed miR-99b serves a prognostic biomarker for OS patients. OS cell proliferation, migration and invasion can be inhibited by the overexpression of miR-99b, suggesting that the methods to increase miR-99b expression may be novel therapeutic strategies in OS.


2013 ◽  
Vol 73 (7) ◽  
pp. 2368-2378 ◽  
Author(s):  
Amanda F. Swindall ◽  
Angelina I. Londoño-Joshi ◽  
Matthew J. Schultz ◽  
Naomi Fineberg ◽  
Donald J. Buchsbaum ◽  
...  

2019 ◽  
Author(s):  
Lukasz Paschke ◽  
Karol Jopek ◽  
Marta Szyszka ◽  
Marianna Tyczewska ◽  
Ludwik Malendowicz ◽  
...  

PeerJ ◽  
2021 ◽  
Vol 9 ◽  
pp. e10810
Author(s):  
Liping Tang ◽  
Shasha Zhu ◽  
Weiyan Peng ◽  
Xuedong Yin ◽  
Cui Tan ◽  
...  

Background Mitogen-activated protein kinase 10 (Mapk10) is a member of the c-jun N-terminal kinases (jnk) subgroup in the MAPK superfamily, and was proposed as a tumor suppressor inactivated epigenetically. Its role in hepatocellular carcinoma (HCC) has not yet been illustrated. We aimed to investigate the expression and epigenetic regulation of mapk10 as well as its clinical significance in HCC. Results Mapk10 was expressed in almost all the normal tissues including liver, while we found that the protein expression of MAPK10 was significantly downregulated in clinical samples of HCC patients compared with these levels in adjacent normal tissues (29/46, P < 0.0001). Clinical significance of MAPK10 expression was then assessed in a cohort of 59 HCC cases, which indicated its negative expression was significantly correlated with advanced tumor stage (P = 0.001), more microsatellite nodules (P = 0.025), higher serum AFP (P = 0.001) and shorter overall survival time of HCC patients. Methylation was further detected in 58% of the HCC cell lines we tested and in 66% of primary HCC tissues by methylation-specific PCR (MSP), which was proved to be correlated with the silenced or downregulated expression of mapk10. To get the mechanisms more clear, the transcriptional silencing of mapk10 was reversed by pharmacological demethylation, and ectopic expression of mapk10 in silenced HCC cell lines significantly inhibited the colony formation ability, induced apoptosis, or enhanced the chemosensitivity of HCC cells to 5-fluorouracil. Conclusion Mapk10 appears to be a functional tumor suppressor gene frequently methylated in HCC, which could be a valuable biomarker or a new diagnosis and therapy target in a clinical setting.


2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e22160-e22160
Author(s):  
Nikolaos Tsoukalas ◽  
Constantinos Giaginis ◽  
Nicolaos Kavantzas ◽  
Paraskevi Alexandrou ◽  
Evangelos Bournakis ◽  
...  

e22160 Background: Ephrin receptors (Ephs) are frequently overexpressed in a wide variety of human malignant tumors, being associated with tumor growth, invasion, metastasis and angiogenesis. The present study aimed toevaluate the clinical significance of Eph-A1, -A4, -A5 and -A7 protein expression in non-small cell lung cancers (NSCLC). Methods: Eph-A1, -A4, -A5 and -A7 protein expression was assessed immunohistochemically in tissue microarrays of 88 surgically resected NSCLC cases and was analyzed in relation with clinicopathological characteristics and patients’ survival. Results: Elevated Eph-A4 expression was significantly associated with earlier or lower stages and histopathological presence of inflammation (p=0.047 and p=0.026, respectively). Elevated Eph-A7 expression was significantly associated with patients’ age, presence of fibrosis and smaller tumor size (p=0.036, p=0.029 and p=0.018, respectively). NSCLC patients with elevatedEph-A4, -A5 or -A7 expression presented significantly longer overall survival times compared to those with reduced Eph-A4, -A5 or -A7 expression (log-rank test, 0=0.019, p=0.006 and p=0.012, respectively). Eph-A4, -A5 and -A7 expression were identified as independent prognostic factors of patients’ survival after adjustment for histopathological type and stage and performance status (Cox-regression analysis, p=0.022, p=0.033 and p=0.037, respectively). Conclusions: The present study supported evidence that Ephs may play a role in lung cancer progression, reinforcing their utility as clinical biomarkers for patients’ management and prognosis, as well as targets for potential therapeutic intervention in the future.


Stroke ◽  
2016 ◽  
Vol 47 (suppl_1) ◽  
Author(s):  
Stephanie M Davis ◽  
Lisa A Collier ◽  
Jawad A Fazal ◽  
Christopher C Leonardo ◽  
Craig T Ajmo ◽  
...  

Objective: To determine whether leukemia inhibitory factor (LIF) upregulates superoxide dismutase 3 (SOD3), a neuroprotective antioxidant enzyme, through the transcription factor myeloid zinc finger-1 (MZF-1). Hypothesis: MZF-1 facilitates LIF-mediated neuroprotection by increasing transcription of the SOD3 gene in neurons. Methods: After middle cerebral artery occlusion or sham surgery, male Sprague-Dawley rats were injected with PBS or LIF (125 μg/kg) (n=4 per group). Rats were euthanized 72 h after injury and western blotting was used to measure MZF-1 protein expression in brain tissue. For in vitro studies, rat neurons were transfected with scrambled or MZF-1 siRNA (n=3 per group). Neurons were treated with PBS or 200 ng/mL LIF prior to 24 h in vitro ischemia induced by oxygen glucose deprivation. Lactate dehydrogenase (LDH) release was measured to assess neuronal death. MZF-1 levels were quantified in cultured neurons with immunocytochemistry. SOD3 and MZF-1 mRNA levels were measured with real-time PCR. Results: LIF (0.938 OD units ± 0.170), but not PBS (0.562 OD units ± 0.223), significantly increased MZF-1 protein expression in ipsilateral tissue 72 h after stroke compared to sham surgery (0.411 OD units ± 0.039, p<0.05). LIF treatment prior to 24 h in vitro ischemia significantly increased the percentage of MZF-1-positive neurons (52.17 % ± 0.93) compared to PBS 44.84 % ± 1.11, p<0.01). PCR results confirmed the increase in MZF-1 mRNA (1.89 fold change ± 0.33) in LIF-treated neurons compared to PBS-treated neurons (1.00 fold change ± 0.23, p<0.05). Moreover, LIF increased SOD3 mRNA after 24 h ischemia (1.35 fold change ± 0.03) compared to PBS (1.00 fold change ± 0.13, p<0.05). LIF decreased LDH release (363,967 ± 68,557 neuronal units) compared to PBS (559,856 ± 60,555 neuronal units, p<0.05) among neurons transfected with scrambled siRNA. However, MZF-1 siRNA attenuated the neuroprotective effect of LIF (690,633 neuronal units ± 19,167; p<0.05). Conclusions: MZF-1 plays a fundamental role in a novel neuroprotective pathway by enhancing SOD3 expression and provides insight regarding protection by antioxidant enzymes during stroke.


BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Jun Ji ◽  
Jiahui Chen ◽  
Anqiang Wang ◽  
Wei Zhang ◽  
Hongge Ju ◽  
...  

Abstract Background The objective of the study was to detect the expression of Kita-Kyushu lung cancer antigen-1 (KK-LC-1) in gastric cancer (GC) specimens and analyse the associations between KK-LC-1 expression and clinicopathological parameters and clinical prognosis. Methods All of the 94 patients in this study were GC patients who underwent surgical resection. KK-LC-1 protein expression in GC tissue was detected by immunohistochemistry. This report applies the histological score (H-score) to evaluate KK-LC-1 expression. To calculate this indicator, the number of positive cells in each section and their staining intensity were converted to corresponding values. The expression of KK-LC-1 in the cytoplasm of cancer and normal tissues was scored to obtain their respective H values. The chi-square test, Kaplan-Meier method and Cox regression were used to analyse the linear association between KK-LC-1 expression and clinicopathological data and prognosis. Results In the cytoplasm, KK-LC-1 expression in tumour tissues was significantly higher than that in normal tissues (P < 0.001). Using the median H-score as the cut-off value, we discovered that GC patients with high levels of KK-LC-1 expression in the cytoplasm had favourable overall survival (OS) (P = 0.016), and this result was statistically significant in the Cox regression analysis. Additionally, a negative correlation was found between KK-LC-1 protein expression and the pathological grade of the tumour (P = 0.036), with significantly more KK-LC-1 protein expression observed in the intestinal type of GC than in the diffuse type (P = 0.008). Conclusions Our research data showed that KK-LC-1 expression was greater in GC tissues than in normal tissues, and higher KK-LC-1 expression was associated with longer OS of GC patients. KK-LC-1 can be used as a biomarker for a good prognosis in GC patients.


2000 ◽  
Vol 111 (4) ◽  
pp. 1118-1121 ◽  
Author(s):  
A. Bellahcene ◽  
I. Van Riet ◽  
C. de Greef ◽  
N. Antoine ◽  
M. F. Young ◽  
...  

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