ABSTRACT
【Objective】 To construct a prognostic model of clear cell renal cell carcinoma (ccRCC) based on endoplasmic reticulum stress (ERS)-related long non-coding ribonucleotides (lncRNA),so as to explore the correlation between immune cell infiltration and prognosis of ccRCC patients,and to search for new drugs for the treatment of ccRCC. 【Methods】 The transcriptome and clinical data of cancerous and paracancerous tissues of ccRCC were obtained from the TCGA database.The ERS-associated gene set was obtained from the MSigDB database.ERS co-expressed lncRNAs were screened with Pearson correlation analysis.ERS-related lncRNA (ERSRL) with prognostic significance were screened with Lasso regression,univariate and multivariate Cox regression analyses,and a prognostic model was constructed.The risk value of each sample was calculated according to the prognostic model formula.The patients were divided into high- risk and low- risk groups for survival difference analysis.The predictive performance of the prognostic model was evaluated with survival curve,receiver operating characteristic (ROC) curve and calibration curve.The infiltration of immune cells in high-and low-risk groups was analyzed with CIBERSORT database.The relationship between ERSRL and drug sensitivity was analyzed with GDSC database to identify drugs with potential efficacy against ccRCC. 【Results】 A total of 9 lncRNAs with independent prognostic significance were screened to construct the prognostic model.Kaplan-Meier analysis showed significant survival differences between the high- and low-risk groups.Univariate and multivariate Cox regression analyses showed that age,grade,stage and risk score could be used as independent prognostic factors.The area under the ROC curve (AUC) of the 1-,3-,and 5-year survival rates of the training set were 0.754 (95%CI:0.659-0.848),0.744 (95%CI:0.667-0.815),and 0.759 (95%CI:0.662-0.820),respectively,and the C-index was 0.777 (95%CI:0.759-0.796).Immune infiltration results showed that plasma cells,activated memory CD4+T cells,regulatory T cells,M0 macrophages,and activated mast cell infiltration levels were higher in the high-risk group than those in the low-risk group.Drug susceptibility analysis identified 12 drugs with potential curative effects on ccRCC,including AZD8055. 【Conclusion】 Based on 9 ERSRLs,a prognostic model for ccRCC patients was constructed,and 12 drugs with potential therapeutic effects were screened,including AZD8055.
ABSTRACT
Objective:To analyze the effect of CD100 to monocyte cytotoxicity in non-small cell lung cancer (NSCLC) patients.Methods:Thirty-five NSCLC patients and thirteen healthy controls were included from Zhengzhou Central Hospital between March 2018 and September 2018. Peripheral blood mononuclear cells (PBMC) and bronchial alveolar lavage fluid (BALF) (both tumor site and non-tumor site) was collected from NSCLC patients, while PBMC was collected from healthy controls. Monocytes were purified from PBMC and BALF. Membrane-bound CD100 (mCD100) and CD72 expression on monocytes was measured by flow cytometry. Monocytes from NSCLC patients were stimulated with recombinant human CD100, anti-CD72, matrix metalloproteinase 14(MMP14), or anti-CD100, and were co-cultured with NCI-H1882 cells for 48 h. Tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), granzyme A, granzyme B level in the supernatants, CD16 expression on monocytes, and percentage of target cell death was assessed. Student t test or paired t test was used for comparison. Results:There were no significant differences of peripheral CD14 + mCD100 + percentage, CD14 + CD72 + percentage, CD100 mean fluorescence intensity (MFI), CD72 MFI between NSCLC patients and healthy controls ( P>0.05). CD14 + mCD100 + percentage, CD14 + CD72 + percentage, CD100 MFI, CD72 MFI was remarkably elevated in tumor site compared with in non-tumor site in NSCLC patients ( P<0.05). There was no remarkable difference of peripheral monocytes-induced NCI-H1882 cell death between NSCLC group and control group [(13.95±3.16)% vs (13.22±2.40)%, P=0.451]. Lung-resident monocytes-induced NCI-H1882 cell death was reduced in tumor site when compared with non-tumor site [(11.61±2.81)% vs (14.19±3.57)%, P=0.008 7]. TNF-α, IL-1β, granzyme A, granzyme B level was also decreased in the supernatants of monocytes from tumor site compared with non-tumor site in NSCLC patients( P<0.05). However, there was no statistical difference of CD16 level between two groups( P=0.666). Recombinant human CD100 stimulation promoted NCI-H1882 cell death induced by monocytes from tumor site when compared with unstimulated cells ( P<0.000 1). TNF-α, IL-1β, granzyme A, granzyme B level was also increased ( P<0.05). However, Monocytes, which were pretreated with anti-CD72, induced decreased NCI-H1882 cell death and TNF-α, IL-1β, granzyme A, granzyme B secretion in response to recombinant human CD100 stimulation ( P<0.05). Recombinant human MMP14 stimulation decreased CD14 + mCD100 + percentage and increased soluble CD100 (sCD100) level. NCI-H1882 cell death and TNF-α, IL-1β, granzyme A, granzyme B level was elevated when compared with unstimulated cells ( P<0.05). Anti-CD100 administration decreased sCD100 level. NCI-H1882 cell death and TNF-α, IL-1β, granzyme A, granzyme B level was elevated when compared with MMP14 stimulated cells ( P<0.05). Conclusions:CD100 shedding was insufficient in tumor infiltrating monocytes in NSCLC patients, leading to decreased cytotoxicity. MMP14 might elevate cytotoxicity of tumor infiltrating monocytes via promoting CD100 shedding and sCD100 formation.
ABSTRACT
Objective To explore the influence of different blood gas strategies on cerebral protection and blood gas analysis during moderate hypothermic cardiopulmonar.Methods Patients under cardiac valve replacement with extracorporeal circulation (ECC) were performed in this study.The cerebral blood flow (CBF) and regional cerebral oxygen saturation (rSO2) were monitored at 5 points:(1)Induction of anesthesia (T1),(2) after 10 min of the beginning of cardiopulmonary bypass (T2),(3) during the moderate hypothermic phase of CBP managed by the alpha-stat after calibrate blood gas 15 min (T3),(4) pH-stat followed,after calibrate blood gas 15 min (T4),and (5) 10 min after CBP (T5).pH and pCO2 in patients were recorded and analyzed at T3 and T4.Results The CBF of T2 and T3 was lower than that of T1,but the difference was not significant (t =2.841,2.711;P =0.062,0.080).The CBF of T4 and T5 was higher than that of T3,but the difference was not significant (t =1.793,2.135;P =0.119,0.066).The CBF of T5 resumed to before operation.The rSO2 of T2 and T3 was lower than that of T1,but the difference was not significant (t =1.821,2.032;P =0.132,0.267),the rSO2 ofT4 and T5 was higher than that ofT3,but the difference was not significant (t =1.879,2.021;P =0.312,0.075).The rSO2 of T5 resumed to before operation.However,the pH was much lower in pH-stat than alpha-stat (t =17.541,P =0.000) and the pCO2 was much higher than alpha-stat (t =13.914,P =0.000).Conclusions Both pH-stat and alpha-stat have cerebral protection effects.However,compared to pH-stat,alpha-stat could reduce the possibility of acidosis,and maintain the acid-base equilibrium.