Effect of CXCR5-Positive Cell Infiltration on the Immune Contexture and Patient Prognosis in Head and Neck Squamous Cell Carcinoma
ONCOTARGETS AND THERAPY
Authors: Chen, Jun; Meng, Xiangchao; Zhou, Qinyi; Feng, Jialin; Zheng, Wenjie; Wang, Zhuoying; Wang, Jiadong; Wang, You
Abstract
Purpose: CXCR5-positive (CXCR5(+)) tumor cell infiltration has different prognostic values in different types of cancer. The objective was to evaluate the effect of CXCR5(+) cell infiltration in head and neck squamous cell carcinoma (HNSCC). Patients and Methods: The study included two patient cohorts: The Cancer Genome Atlas cohort (TCGA, n = 472) and the Renji Hospital cohort (RJHC, n = 201). The TCGA and RJHC cohorts were analyzed for CXCR5-related mRNAs and CXCR5+ cell infiltration, respectively. We then evaluated the correlation between CXCR5 mRNA and CXCR5(+) cell infiltration in terms of overall survival and the immune contexture. Results: The 5-year overall survival rate was significantly correlated with high CXCR5 mRNA expression and CXCR5(+) cell infiltration in the TCGA and RJHC cohorts, respectively (p < 0.01), even after adjusting for confounders. Moreover, high CXCR5 mRNA expression was associated with more CD4(+) T cells, CD8(+) T cells, plasma cells, and less dendritic cells. A high CXCR5 mRNA expression was also correlated with increased expression of cytotoxic IFNG, TNFSF11 (RANKL), GZMA, GZMB, GZMK, GZMM, and PRF1 and increased expression of the immunosuppressive gene PDCD1 (PD-1), CD274 (PD-L1), CTLA4, LAG3, HAVCR2 (TIM-3), BTLA, and TIGIT. Conclusion: HNSCC patients with a high intratumoral CXCR5 expression had a better prognosis than those with low intratumoral CXCR5 expression. Moreover, CXCR5(+) cell infiltration could be used as an independent prognostic biomarker or as a potential therapeutic target. The presence of CXCR5(+) cells affects the infiltration of immunocytes in head and neck cancer, differently from what was reported in other cancer types. Further randomized controlled trials or studies with more patients are needed to validate our results.
A potential marker in brucellosis, long non coding RNA IFNG-AS1
MOLECULAR BIOLOGY REPORTS
Authors: Gheitasi, Reza; Jourghasemi, Sanaz; Pakzad, Iraj; Sarmadi, Vahid Hosseinpour; Samieipour, Yazdan; Sekawi, Zamberi; Jalilian, Farid Azizi
Abstract
Brucellosis is the most common bacterial zoonotic infection. This pathogen may survive and sustain in host. The aim of this study is to define relationship between long noncoding (lnc) RNA-IFNG-AS1 and interferon gamma (IFN-gamma) in different groups of patients with brucellosis compared to control group. In this study, associations of lncRNA IFNG-AS1 expression with secretion of IFN-gamma level in Sixty patients with brucellosis, which were divided into 3 groups (acute, chronic and relapse groups), as a case group were compared with 20 subjects with negative serological tests and brucellosis clinical manifestation as a control group. In this regard, RNA were extracted from isolated peripheral blood mononuclear cells (PBMCs). LncRNA IFNG-AS1, T-box transcription factor (T-bet) and IFN-gamma expressions were detected using quantitative polymerase chain reaction (qPCR). Serum level IFN-gamma was assessed using enzyme linked immunosorbent assay (ELISA). The results showed that expression level of LncRNA IFNG-AS1, T-bet and IFN-gamma increased significantly in all patient groups in compared to healthy subjects (P<0.0001, P<0.01, P<0.001). However, there was no significant difference in T-bet expression between chronic and healthy groups (P=0.98). Additionally, further analysis revealed that the serum level of IFN-gamma in acute and relapsed groups were higher than control group (P<0.0001, P<0.001). The effective role of IFNG-AS1 in many protective actions, including enhancing the expression of INF-gamma in the immune response of brucellosis patients, revealed new potential marker, LncRNA IFNG-AS1 in screening, diagnosis or treatment of brucellosis.