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Objective@#This study aimed to reveal the potential clinical and biological functions of frizzled related protein (FRZB) mRNA expression in lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC). @*Methods@#We used the keyword “lung cancer” to search the data through Gene Expression Omnibus (GEO) database attached to NCBI(National Center of Biotechnology) and download the data of LUAD and LUSC from TCGA (The Cancer Genome Atlas) Database. A total of eight LUAD and six LUSC datasets were incorporated in this analysis. We defined cutoff value of FRZB using Cutoff Finder into the two groups to calculate hazard ratio (HR). @*Results@#We found that high expression level of FRZB mRNA in tumor tissues was a positive prognostic factor for overall survival in LUAD [pooled HR（95%CI）=0.54（0.46-0.64）,P＜0.05 in univariate analysis; pooled HR（95%CI）=0.66（0.54-0.79）,P＜0.05 in multivariate analysis]. Interestingly, there was no similar results in LUSC [pooled HR（95%CI）=1.11（0.67-1.84）,P＞0.05 in univariate analysis; pooled HR（95%CI）=1.13（0.71-1.78）,P＞0.05 in multivariate analysis]. We also found that FRZB may inhibit WNT signal pathway by t-SNE and correlation analysis. By enrichment analysis, FRZB and its most correlated genes were involved in multiple immune-related pathways, such as complement and coagulation cascades, humoral immune response, etc. @*Conclusion@#High expression of FRZB mRNA in LUAD was associated with better prognosis of lung adenocarcinoma. These results suggest that FRZB may be used as a potential marker for favorable prognosis of lung adenocarcinoma.
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Objective@#To investigate the degree of infiltration and distribution of tissue-resident CD8 + T cells (CD103 + CD8 + T cells) in gastric cancer tissues, and analyze the relationship between the degree of infiltration and clinicopathological features and prognosis. @*Methods@#Tissue microarray and immunofluorescence staining were used to examine the CD8 + T cells and CD103 + CD8 + T cells infiltration in 90 cases of gastric cancer and their adjacent normal tissues. Wilcoxon rank test was used to compare the CD8 + T cells, CD103 + CD8 + T cells infiltration and CD103 + CD8 + T cells/CD8 + T cells ratio in gastric cancer and corresponding normal tissues. The chi-square test was used to analyze the relationship between CD8 + T cells, CD103 + CD8 + T cells infiltration and CD103 + CD8 + T cells/ CD8 + T cells ratio in gastric cancer tissues and clinicopathological features of the patients. Kaplan-Meier survival analysis was performed to explore the correlation between CD8 + T cells, CD103 + CD8 + T cells infiltration and CD103 + CD8 + T cells/ CD8 + T cells ratio and overall survival. Cox model was used to analyze the correlation between different clinical parameters and prognosis of the patients. @*Results@#There was no significant difference for the infiltration of CD103 + CD8 + T cells between the gastric cancer tissues and adjacent normal tissues (P＞0.05). The infiltration rate of CD103 + CD8 + T cells in the cases in stage Ⅲ to Ⅳ (69.09%, 38/55) was significantly lower than that in the stage Ⅰ to Ⅱ cases (91.43%, 32/35), (χ 2 =6.175, P=0.013). There was no significant correlation between CD103 + CD8 + T cells infiltration and other clinicopathological features (P＞0.05). Kaplan-Meier survival analysis showed that the patients with high CD103 + CD8 + T cells infiltration showed significantly longer overall survival than the patients with low CD103 + CD8 + T cells infiltration (HR=2.187, 95%CI: 1.062-4.500, P=0.033 6). Multivariate Cox model analysis indicated that tumor diameter (HR=2.031, 95%CI: 1.163-3.546, P=0.013) and CD103 + CD8 + T cells infiltration (HR=0.516, 95%CI: 0.285-0.934, P=0.029) were independent prognostic factors for gastric cancer. @*Conclusion@#CD103 + CD8 + T cells in gastric cancer tissues should be associated with good prognosis, suggesting that they play an important role in the inhibition of gastric carcinogenesis and development, and can be used as an important factor for the prognosis evaluation of the patients with gastric cancer.
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Objective To purify the anti-T cell immunoglobulin mucin ( TIM)-3 monoclonal antibody 4E8 and examine its biological function in vitro. Methods The mouse monoclonal antibody against human TIM-3, clone 4E8, was obtained by standard protocol for monoclonal antibody purification. The cell lines expressing human TIM-3 molecule were obtained by cell transfection technique. We ex-amined the ability of 4E8 binding to human TIM-3 by flow cytometry. The ability of 4E8 blocking the binding of fusion protein TIM-3 Ig-huFc with phosphatidylserine( PtdSer) , the apoptotic cell surface TIM-3 ligand, was also analyzed by flow cytometry. Mixed lympho-cyte reaction ( MLR) and ELISA assays were used to determine the effect of TIM-3 monoclonal antibody ( 4E8) on IFN-γsecretion in CD4+ T cells. Results 4E8 specifically bound to human TIM-3 but could not block the binding of TIM-3 to Ptdser. Compared with the negative control (IFN-γ secretion: 958.3±153.2), 4E8 enhanced the ability of CD4+ T cells to secrete IFN-γ in MLR (4E8 of 10μg/mL group:IFN-γ secretion 2563±150.3 and 4E8 of 3.33 μg/mL group:IFN-γ secretion 1981±211.5) with statistically signifi-cant difference ( P<0.05) . In addition, the combined application of 4E8 with the anti-programmed death-1 ( PD-1) monoclonal anti-body nivolumab showed synergistic effects for increasing IFN-γ secretion in MLR assay ( 4E8 of 10 μg/mL group: IFN-γ secretion 3049±80.5 and 4E8 of 0.33μg/mL group:IFN-γsecretion 1957±321.3) as compared with 4E8 alone (10μg /mL group:IFN-γse-cretion 2563±150.3 and 0.33 μg/mL group:IFN-γ secretion 844±76.2) with statistically significant difference (P<0.05). Conclu-sion We successfully obtained a 4E8 clone of monoclonal antibody to human TIM-3 which may enhance the capacity of IFN-γsecre-tion from CD4+ T cells. The effect of enhancing IFN-γ secretion of CD4+T cells by TIM-3 monoclonal antibody was independent from blocking the binding of TIM-3 with Ptdser.
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Objective To investigate the relevance between the times of cytokine-induced killer cell (CIK cell) adoptive immunotherapy and the survival of the elderly patients with gastric cancer.Methods Lymphocyte separation medium was used to isolate mononuclear cells, and then the cultured CIK cells were infused back into the patients with gastric cancer. A retrospective cohort study was adopted by using Kaplan-Meier to estimate median survival time and survival rate, using Log-rank test to analyze the impact of clinical factors on survival rate, and using RR and 95% CI to estimate the contact intensity of death outcome, survival time and CIK cell treatment. Results There were nostatistically significant differences in gender,age, tumor site, histological type, invasion depth, lymph node metastasis, pathological grade, tumor size or tumor distribution between chemotherapy group and CIK treatment group (all P＞0.05). The median survival time of patients with gastric cancer was significantly longer in CIK treatment group than in chemotherapy group (61 vs. 21, χ2=10.215, P=0.001). Compared with the patients treated by chemotherapy alone, the increased times of CIK treatment induced more survival rate and 2-5 years life spans (χ2=12. 461, P=0.006). Conclusions With the treatment that CIK cells are infused back into the elderly patients with gastric cancer, the risk of death is reduced, and the lifespan is prolonged, which is associated with the CIK cell treatment times.