Ata Miyar1, Iman Habibi2, Ali Ebrahimi3, Delaram Mansourpour4, Aram Mokarizadeh5, Alireza Rajabi6, Rozhin Farshgar7, Mehdi Eshaghzadeh2, Mohamad Zamani-Ahmadmahmudi8, Seyed Mohamad Hossein Tabatabaei Nodushan2. 1. Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Iran. 2. Faculty of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran. 3. Students' Research Committee, Baqiyatallah University of Medical Sciences, Tehran, Iran. 4. Brain and Spinal Cord Injury Research Center, Neuroscience Institute, Tehran University of Medical Sciences, Tehran, Iran. 5. Cellular & Molecular Research Center, Kurdistan University of Medical Sciences, Sanandaj, Iran. 6. Graduated from the Faculty of Veterinary Medicine, Islamic Azad University, Karaj Branch, Karaj, Iran. 7. Veterinarian in Private Sector. Electronic address: rozhinfarshgar3000@gmail.com. 8. Department of Clinical Sciences, Faculty of Veterinary Medicine, Shahid Bahonar University of Kerman, Kerman, Iran.
Abstract
BACKGROUND: Malignant gliomas are the most common form of primary intracranial tumors with the highest mortality rates. Various gene alterations are considered as prognostic markers in glioma. But, the relevant molecular mechanisms in this setting are not well-understood. OBJECTIVE: The aim of this study was to assess the association and prognostic value of TLR9 and NFKBIA with clinical significance and also their impact on patient survival in human glioma. METHODS: Expression of TLR9 and NFKBIA mRNA in the tissues was determined by immunohistochemistry and qRT-PCR methods. Kaplan-Meier curves and Cox proportional hazards regression model were used to assess the association of TLR9 and NFKBIA with clinical outcomes of patients. RESULTS: Quantitative real-time PCR analysis showed that TLR9 mRNAs is markedly expressed in glioma tissues than in non-neoplastic tissues (mean±SD: 3.26±0.40 vs. 0.71±0.36, P<0.001). There was also a significant difference between TLR9 mRNAs and high grade glioma (P<0.001).NFKBIA mRNAs was significantly identified in non-neoplastic tissues compared with glioma specimens (mean±SD: 2.76±0.30 vs. 0.94±0.35, P<0.001). Lower levels of NFKBIA mRNA were significantly related to advanced grade of gliomas (P<0.001). Furthermore, Immunoreactivity for high expression of TLR9 was detected in 65% of cases (26/40) that was associated with high grade glioma (P=0.001). No statistically significant correlation was found between TLR9 and other clinical parameters (P>0.05). Immunoreactivity for high expression of NFKBIA was observed in 32.5% (13/40) of cases and NFKBIA expression was decreased in patients with high grad glioma (P=0.014). There was no significant correlation between NFKBIA protein expression and age, sex, and relapse. The Kaplan-Meier analysis indicated that patients with high expression of TLR9 and low expression of NFKBIA are significantly related to poorer OS (P<0.001). In addition, the multivariate Cox regression model revealed that TLR9 and NFKBIA protein expressions (low/high) and tumor grade were potentially an independent predictor of survival in patients (hazard ratio, 2.132, 2.411, 2.13 [95% confidence interval, 1.825-3.782, 1.61-3.231, 1.542-3.92]; P=0.012,P=0.018, P=0.001). CONCLUSION: These data indicate that TLR9 and NFKBIA protein expressions act as independent predictor of survival for the diagnosis of glioma and a prognostic biomarker for those with a tumor at an advanced pathological grade.
BACKGROUND:Malignant gliomas are the most common form of primary intracranial tumors with the highest mortality rates. Various gene alterations are considered as prognostic markers in glioma. But, the relevant molecular mechanisms in this setting are not well-understood. OBJECTIVE: The aim of this study was to assess the association and prognostic value of TLR9 and NFKBIA with clinical significance and also their impact on patient survival in humanglioma. METHODS: Expression of TLR9 and NFKBIA mRNA in the tissues was determined by immunohistochemistry and qRT-PCR methods. Kaplan-Meier curves and Cox proportional hazards regression model were used to assess the association of TLR9 and NFKBIA with clinical outcomes of patients. RESULTS: Quantitative real-time PCR analysis showed that TLR9 mRNAs is markedly expressed in glioma tissues than in non-neoplastic tissues (mean±SD: 3.26±0.40 vs. 0.71±0.36, P<0.001). There was also a significant difference between TLR9 mRNAs and high grade glioma (P<0.001).NFKBIA mRNAs was significantly identified in non-neoplastic tissues compared with glioma specimens (mean±SD: 2.76±0.30 vs. 0.94±0.35, P<0.001). Lower levels of NFKBIA mRNA were significantly related to advanced grade of gliomas (P<0.001). Furthermore, Immunoreactivity for high expression of TLR9 was detected in 65% of cases (26/40) that was associated with high grade glioma (P=0.001). No statistically significant correlation was found between TLR9 and other clinical parameters (P>0.05). Immunoreactivity for high expression of NFKBIA was observed in 32.5% (13/40) of cases and NFKBIA expression was decreased in patients with high grad glioma (P=0.014). There was no significant correlation between NFKBIA protein expression and age, sex, and relapse. The Kaplan-Meier analysis indicated that patients with high expression of TLR9 and low expression of NFKBIA are significantly related to poorer OS (P<0.001). In addition, the multivariate Cox regression model revealed that TLR9 and NFKBIA protein expressions (low/high) and tumor grade were potentially an independent predictor of survival in patients (hazard ratio, 2.132, 2.411, 2.13 [95% confidence interval, 1.825-3.782, 1.61-3.231, 1.542-3.92]; P=0.012,P=0.018, P=0.001). CONCLUSION: These data indicate that TLR9 and NFKBIA protein expressions act as independent predictor of survival for the diagnosis of glioma and a prognostic biomarker for those with a tumor at an advanced pathological grade.
Authors: Jun Wei; Renduo Song; Aria Sabbagh; Anantha Marisetty; Neal Shukla; Dexing Fang; Hinda Najem; Martina Ott; James Long; Lijie Zhai; Maciej S Lesniak; Charles David James; Leonidas Platanias; Michael Curran; Amy B Heimberger Journal: Oncoimmunology Date: 2022-04-13 Impact factor: 7.723
Authors: Mei Hong; Jing He; Duo Li; Yuanyuan Chu; Jiarui Pu; Qiangsong Tong; Harish C Joshi; Shaotao Tang; Shiwang Li Journal: J Exp Clin Cancer Res Date: 2020-03-20