scholarly journals High-Level Expression of RIPK4 and EZH2 Contributes to Lymph Node Metastasis and Predicts Favorable Prognosis in Patients With Cervical Cancer

Author(s):  
Susan Azizmohammadi ◽  
Sima Azizmohammadi ◽  
Aghdas Safari ◽  
Maria Kaghazian ◽  
Mina Sadrkhanlo ◽  
...  

The investigation of specific genes will establish more useful biomarkers for accurate detection and management of gynecological cancers, especially patients with cervical cancer (CCP). The aim of this study was to evaluate the expression level of RIPK4 and EZH2 messenger RNA (RIPK4 and EZH2 mRNA) in CCP. Expression of RIPK4 and EZH2 in the tissues was determined by immunohistochemistry and qRT-PCR methods. Correlations of RIPK4 and EZH2 mRNA with clinical and pathological parameters were analyzed using the Fisher’s exact test. The mRNA level of RIPK4 was significantly upregulated in tumor tissues compared with matched adjacent normal tissues (4.10 ± 0.89 vs. 1.5 ± 0.82; p = 0.021). EZH2 mRNA was increased in cancer tissues compared to normal tissues (3.54 ± 0.71 vs. 1.2 ± 0.65; p = 0.003). High expression of RIPK4 was observed in 25 patients (64.1%), whereas weak expression was seen in 14 cases (35.9%). Furthermore, the expression of RIPK4 was overexpressed in matched adjacent normal tissues (p = 0.004). FIGO stage and lymph node metastasis were significantly linked to a higher expression of RIPK4 (p < 0.05). Overexpression of EZH2 was found in 30 patients (76.9%) and was associated with FIGO stage, histological type, and lymph node metastasis (p < 0.05). In conclusion, our data suggest that RIPK4/EZH2 markers might be used as potential predictors of prognosis in cervical cancer.

2018 ◽  
Vol 2018 ◽  
pp. 1-10 ◽  
Author(s):  
Chiara Tuccilli ◽  
Enke Baldini ◽  
Salvatore Sorrenti ◽  
Antonio Catania ◽  
Alessandro Antonelli ◽  
...  

The dysregulation of PD-1 ligands (PD-L1 and PD-L2) and CTLA-4 ligands (CD80 and CD86) represents a tumor strategy to escape the immune surveillance. Here, the expression of PD-L1, PD-L2, CD80, and CD86 was evaluated at the mRNA level in 94 patients affected by papillary thyroid carcinoma (PTC) and 11 patients affected by anaplastic thyroid carcinoma (ATC). Variations in the mRNAs in PTC patients were then correlated with clinicopathological features. The expression of all genes was deregulated in PTC and ATC tissues compared to normal tissues. In particular, the downregulation of CD80 was observed above all in ATC. In addition, the increased expression of CD80 associated with longer disease-free survival in PTC. Higher expression of PD-L1 associated with the classical histological variant and with the presence of BRAFV600E mutation in PTC. The increased PD-L2 expression correlated with BRAFV600E mutation and lymph node metastasis, while its lower expression correlated with the follicular PTC variant. The latter was also associated with the CD80 downregulation, which was also related to the absence of lymph node metastasis. In conclusion, we documented the overall dysregulation of PD-1 and CTLA-4 ligands in PTC and ATC tissues and a possible prognostic value for CD80 gene expression in PTC.


2005 ◽  
Vol 99 (3) ◽  
pp. 790-791 ◽  
Author(s):  
A BADER ◽  
K TAMUSSINO ◽  
O REICH ◽  
R WINTER

2019 ◽  
Vol 5 (suppl) ◽  
pp. 62-62
Author(s):  
Qin Xu ◽  
Yibin Lin ◽  
Xian Lin ◽  
Jing Liu ◽  
Li Li ◽  
...  

62 Background: To better understand the mechanism contributing to cervical carcinogenesis, we perform a comprehensive analysis of genomic alterations in cervical cancer (CC). Methods: We conducted whole-exome sequencing of 43 CCs and established strict integrated workflow of genomic analysis. Correlation analysis was performed to measure the relationships between gene mutations and clinical characteristics of CC patients. Results: Genomic analysis revealed 28 genes frequently mutated in CC including BRD4 (4/43), AXL (4/43), MED12 (4/43), which are undetermined genomic features in CC, and identified recurrent genetic mutations in PIK3CA (16/43), KMT2D (11/43), KMT2C (6/43), FBXW7 (5/43), FAT1 (5/43), ERBB2 (4/43), EP300 (3/43) and NFE2L2 (3/43). Intriguingly, CC patients harbored high frequent mutations in BRCA2 (7/43), but not in BRCA1. The relationship between BRCA2 mutations and clinical factors is yet to be determined. The identified mutations predominately resulted in the dysregulation of the PI3K/AKT/mTOR pathway. Interestingly, we found that AXL mutations were positively correlated with FIGO stage ( P = 0.028), regional lymph node metastasis ( P = 0.011) and distant metastasis ( P = 0.022). KMT2C mutations were positively correlated with FIGO stage ( P = 0.004) and distant metastasis ( P = 0.009). SF3B1 mutations were positively correlated with regional lymph node metastasis ( P = 0.027) and distant metastasis ( P< 0.001). NFE2L2, ERBB2, RAC1, MED12, MET, BAP1, PTPRD and HNF1Amutations were positively correlated with distant metastasis ( P = 0.045, P = 0.004, P = 0.022, P = 0.001, P< 0.001, P< 0.001, P = 0.014, P< 0.001, respectively). POLD1 mutations were positively associated with regional lymph node metastasis ( P = 0.029). However, NOTCH1 mutations were negatively associated with regional lymph node metastasis ( P = 0.047). STK11 mutations were negatively associated with FIGO stage ( P = 0.013). Conclusions: Our results highlight the application of deep sequencing for understanding the molecular mechanisms and uncovering potential diagnostic and therapeutic targets of CC.


2020 ◽  
Author(s):  
Fan Guo ◽  
Wei na Kong ◽  
Gang Zhao ◽  
Zhen zhen Cheng ◽  
Le Ai ◽  
...  

Abstract Background: Tumor microenvironment (TME) plays a particularly important role in the progression, invasion and metastasis of cervical carcinoma (CC). Tumor-associated macrophages (TAMs) are significant components of cervical cancer microenvironment. However, the result of studies on the correlation between TAMs and progression in CC is still controversial. This research is aimed at investigating the relationship between TAMs and progression in CC.Method: A total of 100 patients with CC were included in this study. The correlation between TAMs and clinicopathologic features was studied. Also, a systematic literature search was conducted from legitimate electronic databases. This is the first meta-analysis to specifically evaluate the role of different types of TAMs in TME of cervical cancer.Results: In the meta-analysis, high stromal CD68+ TAMs density was relevant to lymph node metastasis (WMD = 11.89, 95% CI 5.30 to 18.47). At the same time, CD163+ M2 TAM density was associated with lymph node metastasis (OR = 2.42, 95% CI 1.09 to 5.37; WMD = 39.37, 95% CI 28.25 to 50.49) and International Federation of Obstetrics and Gynecology (FIGO) stage (WMD = -33.60, 95% CI -45.04 to -22.16). This was confirmed in 100 experimental studies of CC. It supported a critical role of TAMs as a prospective predictor for cervical cancer.Conclusion: Taken together, CD68+ TAM and CD163+ M2 TAM infiltration in cervical cancer was association with tumor progression. And CD163+ M2 TAM infiltration was associated with more advanced FIGO stage and lymph node metastasis in CC.


2021 ◽  
Author(s):  
Fan Guo ◽  
Wei na Kong ◽  
Gang Zhao ◽  
Zhen zhen Cheng ◽  
Le Ai ◽  
...  

Tumor microenvironment (TME) plays a particularly important role in the progression, invasion and metastasis of cervical carcinoma (CC). Tumor-associated macrophages (TAMs) are significant components of the tumor microenvironment in CC. However, the results of studies on the correlation between TAMs and progression in CC are still controversial. This research aimed to investigate the relationship between TAMs infiltration and progression in CC. A total of 100 patients with CC were included in the study. The correlation between TAMs and clinicopathologic features was studied. Besides, a systematic literature search was conducted from legitimate electronic databases to specifically evaluate the role of TAMs in TME of cervical carcinoma. In the meta-analysis, high stromal CD68+ TAMs density was relevant to lymph node metastasis (WMD = 11.89, 95% CI 5.30 to 18.47). At the same time, CD163+ M2 TAM density was associated with lymph node metastasis (OR = 2.42, 95% CI 1.09 to 5.37; WMD = 39.37, 95% CI 28.25 to 50.49) and FIGO stage (WMD = -33.60, 95% CI -45.04 to -22.16). This was further confirmed in the experimental study of 100 tissues of cervical cancer. It supported a critical role of TAMs as a prospective predictor of cervical cancer. In conclusion, CD68+ TAM and CD163+ M2 TAM infiltration in CC were associated with tumor progression. And CD163+ M2 TAM infiltration was associated with more advanced FIGO stage and lymph node metastasis in CC.


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