scholarly journals The Expression of PD-L1 and B7-H4 in Thymic Epithelial Tumor and Its Relationship With Tumor Immune-Infiltrating Cells

2021 ◽  
Vol 11 ◽  
Author(s):  
Xiaotian Yan ◽  
Jie Feng ◽  
Bo Hong ◽  
Yun Qian

BackgroundPD-L1 and B7-H4 have been reported to be expressed in various malignancies and are considered as promising prognostic factors and potential immunotherapy targets.MethodsWe analyzed the correlation between the expression of PD-L1 and B7-H4 transcriptomes and clinicopathological characteristics in 121 TET patients from The Cancer Genome Atlas (TCGA) database. The immune-infiltration levels in the TET microenvironment were estimated using ssGSEA and quanTiseq algorithms. We collected 80 TET cases from 2008 to 2015. PD-L1、B7-H4、FOXP3 and CD163 protein expression in tumor tissues were detected by immunohistochemistry.ResultsTCGA database showed PD-L1 mRNA levels can predict the OS (P = 0.018) and DFS (P = 0.033) of TET patients. B7-H4 mRNA levels were positively related to the World Health Organization (WHO) pathological classification (P = 0.003) but not correlated with patient prognosis. Immune infiltration analysis showed PD-L1 is positively correlated with Tregs and M2 macrophages, B7-H4 is positively correlated with Tregs. Patients with high PD-L1 and Tregs or M2 macrophages, high B7-H4 and Tregs had a worse prognosis. Immunohistochemistry showed PD-L1 expression was positively correlated with the WHO pathological classification and Masaoka stage (P = 0.025, 0.003) and high PD-L1 expression can predict the poor OS of patients (P = 0.043); B7-H4 was also positively correlated with WHO pathological classification and Masaoka stage (P = 0.036, 0.049). However, B7-H4 expression did not correlate with patient prognosis. Evaluation of co-expression patterns showed TET patients with a high-grade WHO pathological classification harbored a 44.4% co-expression of PD-L1 and B7-H4. In addition, we found the expression level of PD-L1 is positively correlated with FOXP3 and CD163 (P = 0.004, P = 0.029) and B7-H4 is positively correlated with FOXP3 (P = 0.037). High PD-L1 combined with High FOXP3 and High CD163, High B7-H4 combined with High FOXP3 can be used to predict the poor prognosis of TET patients (P = 0.026, 0.031, 0.028, respectively).ConclusionPD-L1 and B7-H4 were related to the aggressiveness of TET and their expression level can indicate the suppressive immune microenvironment. Combined with FOXP3 and CD163, PD-L1 and B7-H4 can indicate a poor prognosis of TET.

2021 ◽  
Author(s):  
Jiaxi Feng ◽  
Yanan Hu ◽  
Dan Liu ◽  
Shanshan Wang ◽  
Mengci Zhang ◽  
...  

Abstract Background Breast cancer (BC) is the most common malignant tumor in women and widely known for its poor prognosis. More and more research has discovered that cyclin E1 (CCNE1) plays an important role in progression of various types of cancer. But its specific mechanism in BC progression still needs further research to explore.Methods At first, we determined the expression and prognostic value of CCNE1 through The Cancer Genome Atlas (TCGA) database and The Genotype-Tissue Expression (GTEx) data. Then, we predicted the upstream non-coding RNAs of CCNE1 through StarBase, GEPIA, and Kaplan-Meier plotter database. We further studied the correlation of CCNE1 expression with BC immune cell infiltration, biomarkers of immune cells and immune checkpoints expression through TIMER and GEPIA databases.Results The results suggested that CCNE1 was significantly upregulated in BC and its high expression was correlated with poor prognosis in BC patients. Next, we identified long noncoding RNA (lncRNA) LINC00511 / microRNA-195-5p (miR-195-5p) / CCNE1 axis as the most potential pathway that could regulate CCNE1 expression in BC through StarBase, GEPIA, and Kaplan-Meier plotter database. Furthermore, our in-depth research discovered that CCNE1 expression level was significantly correlated with tumor immune cell infiltration, biomarkers of immune cells, and immune checkpoint expression in BC. conclusions In summary, high expression level of CCNE1 was significantly correlated with poor prognosis, tumor immune infiltration and escape in BC.


2021 ◽  
Author(s):  
Yisheng Peng ◽  
Jun Fan ◽  
Gang Zhu ◽  
Shunde Tan ◽  
Jianfei Chen ◽  
...  

Abstract Background: According to reports, LIMK1 may have the effect of promoting tumor progression. However, the effect of the expression of LIMK1 on the healing of patients with hepatocellular carcinoma and its effect on the immune function are still not clear. Therefore, we analyzed the effect of LIMK1 on the healing of patients with hepatocellular carcinoma and its correlation with immunity through bioinformatics analysis.Methods: Download the transcriptional expression profile of LIMK1 in hepatocellular carcinoma tissues and normal tissues in TCGA, and study its expression in hepatocellular carcinoma. Study the expression of LIMK1 in hepatocellular carcinoma through CPTAC and HPA database. The Kaplan-Meier method was used to evaluate the effect of LIMK1 expression on the survival of patients with hepatocellular carcinoma. Use the STRING database to construct a protein-protein interaction (PPI) network. Use the "ClusterProfiler" package for feature-rich analysis. Use TISIDB database and Xiantao platform to study the relationship between LIMK1 mRNA expression and immune infiltration.Results: The expression of LIMK1 in hepatocellular carcinoma tissues was significantly up-regulated. Increased expression of LIMK1 mRNA is related to high TNM staging. In the ROC curve, when the cut-off level is 1.813, the sensitivity and specificity of LIMK1 to distinguish hepatocellular carcinoma from adjacent controls are 80.7% and 86%, respectively.The Kaplan-Meier curve shows that the higher the expression of LIMK1, the worse the survival of patients with hepatocellular carcinoma (42.2 months vs. 70 months, P = 0.001). Correlation analysis studies have shown that the expression of LIMK1 mRNA in hepatocellular carcinoma is related to immune cell infiltration.Conclusion: Up-regulation of LIMK1 may affect the survival rate and immune invasion of hepatocellular carcinoma. Studies have shown that LIMK1 may be related to the poor prognosis of hepatocellular carcinoma, and has a certain relationship with the immune infiltration of hepatocellular carcinoma.


2021 ◽  
Author(s):  
Jiaxi Feng ◽  
Yanan Hu ◽  
Dan Liu ◽  
Shanshan Wang ◽  
Mengci Zhang ◽  
...  

Abstract BackgroundBreast cancer (BC) is the most common malignant tumor in women and widely known for its poor prognosis. More and more research has discovered that cyclin E1 (CCNE1) plays an important role in progression of various types of cancer. But its specific mechanism in BC progression still needs further research to explore.MethodsAt first, we determined the expression and prognostic value of CCNE1 through The Cancer Genome Atlas (TCGA) database and The Genotype-Tissue Expression (GTEx) data. Then, we predicted the upstream non-coding RNAs of CCNE1 through StarBase, GEPIA, and Kaplan-Meier plotter database. We further studied the correlation of CCNE1 expression with BC immune cell infiltration, biomarkers of immune cells and immune checkpoints expression through TIMER and GEPIA databases.ResultsThe results suggested that CCNE1 was significantly upregulated in BC and its high expression was correlated with poor prognosis in BC patients. Next, we identified long noncoding RNA (lncRNA) LINC00511 / microRNA-195-5p (miR-195-5p) / CCNE1 axis as the most potential pathway that could regulate CCNE1 expression in BC through StarBase, GEPIA, and Kaplan-Meier plotter database. Furthermore, our in-depth research discovered that CCNE1 expression level was significantly correlated with tumor immune cell infiltration, biomarkers of immune cells, and immune checkpoint expression in BC.ConclusionIn summary, high expression level of CCNE1 was significantly correlated with poor prognosis, tumor immune infiltration and escape in BC.


2021 ◽  
Author(s):  
Xiangyi Chen ◽  
Dechen Yu ◽  
Hai-Yu Zhou ◽  
XiaoBo Zhang ◽  
Yicun Hu ◽  
...  

Abstract Background: The primary function of the Karyophorin alpha family (KPNAs) is to assist the transport of proteins from the cytoplasm to the nucleus. Studies have found that KPNAs are involved in the occurrence and development of a variety of tumors. However, the expression level of KPNAs family members in HCC, its influence on prognosis, its relationship with immune infiltration, and its clinical significance are still unclear.Methods: We used UALCAN, GEPIA, HPA, TIMER, Kaplan-Meier Plotter, CBioPortal, String and Metascape databases to analyze the expression and mutation of KPNAs in Hepatocellular carcinoma (HCC), the expression level of KPNAs and the prognosis of patients, tumor immune cell infiltration, HCC clinicopathological characteristics Relationship. Finally, the biological functions of KPNAs related genes are analyzed. Results: The protein and mRNA of KPNAs were significantly up-regulated in HCC, and their expression levels were closely related to the prognosis of patients and the clinical characteristics of the tumor (tumor grade, stage, etc.). In addition, KPNAs in HCC are prone to mutations, which are not conducive to the prognosis of patients. Moreover, the expression of HCC is positively correlated with the infiltration of immune cells. Enrichment analysis found that KPNAs-related genes are mainly related to biological processes such as nuclear and cytoplasmic signaling, protein chromosome localization, and their pathways mainly include cell cycle and MAPK signaling pathways. Conclusion: KPNAs are significantly related to the occurrence, development and patient prognosis of HCC and may become the target of HCC immunotherapy in the future.


2021 ◽  
Vol 20 ◽  
pp. 153303382110330
Author(s):  
Lulu Yin ◽  
Yan Liu ◽  
Xi Zhang ◽  
Hongbing Lu ◽  
Yang Liu

Intratumor heterogeneity is partly responsible for the poor prognosis of glioblastoma (GBM) patients. In this study, we aimed to assess the effect of different heterogeneous subregions of GBM on overall survival (OS) stratification. A total of 105 GBM patients were retrospectively enrolled and divided into long-term and short-term OS groups. Four MRI sequences, including contrast-enhanced T1-weighted imaging (T1C), T1, T2, and FLAIR, were collected for each patient. Then, 4 heterogeneous subregions, i.e. the region of entire abnormality (rEA), the regions of contrast-enhanced tumor (rCET), necrosis (rNec) and edema/non-contrast-enhanced tumor (rE/nCET), were manually drawn from the 4 MRI sequences. For each subregion, 50 radiomics features were extracted. The stratification performance of 4 heterogeneous subregions, as well as the performances of 4 MRI sequences, was evaluated both alone and in combination. Our results showed that rEA was superior in stratifying long-and short-term OS. For the 4 MRI sequences used in this study, the FLAIR sequence demonstrated the best performance of survival stratification based on the manual delineation of heterogeneous subregions. Our results suggest that heterogeneous subregions of GBMs contain different prognostic information, which should be considered when investigating survival stratification in patients with GBM.


Author(s):  
Juan Tong ◽  
Lei Zhang ◽  
Huilan Liu ◽  
Xiucai Xu ◽  
Changcheng Zheng ◽  
...  

AbstractThis is a retrospective study comparing the effectiveness of umbilical cord blood transplantation (UCBT) and chemotherapy for patients in the first complete remission period for acute myeloid leukemia with KMT2A-MLLT3 rearrangements. A total of 22 patients were included, all of whom achieved first complete remission (CR1) through 1–2 rounds of induction chemotherapy, excluding patients with an early relapse. Twelve patients were treated with UCBT, and 10 patients were treated with chemotherapy after 2 to 4 courses of consolidation therapy. The 3-year overall survival (OS) of the UCBT group was 71.3% (95% CI, 34.4–89.8%), and that of the chemotherapy group was 10% (95% CI, 5.89–37.3%). The OS of the UCBT group was significantly higher than that of the chemotherapy group (P = 0.003). The disease-free survival (DFS) of the UCBT group was 60.8% (95% CI, 25.0–83.6%), which was significantly higher than the 10% (95% CI, 5.72–35.8%) of the chemotherapy group (P = 0.003). The relapse rate of the UCBT group was 23.6% (95% CI, 0–46.8%), and that of the chemotherapy group was 85.4% (95% CI, 35.8–98.4%), which was significantly higher than that of the UCBT group (P < 0.001). The non-relapse mortality (NRM) rate in the UCBT group was 19.8% (95% CI, 0–41.3%), and that in the chemotherapy group was 0.0%. The NRM rate in the UCBT group was higher than that in the chemotherapy group, but there was no significant difference between the two groups (P = 0.272). Two patients in the UCBT group relapsed, two died of acute and chronic GVHD, and one patient developed chronic GVHD 140 days after UCBT and is still alive, so the GVHD-free/relapse-free survival (GRFS) was 50% (95% CI, 17.2–76.1%). AML patients with KMT2A-MLLT3 rearrangements who receive chemotherapy as their consolidation therapy after CR1 have a very poor prognosis. UCBT can overcome the poor prognosis and significantly improve survival, and the GRFS for these patients is very good. We suggest that UCBT is a better choice than chemotherapy for KMT2A-MLLT3 patients.


2019 ◽  
Vol 2019 ◽  
pp. 1-13
Author(s):  
Jie Zhang ◽  
Qianqian Song ◽  
Jinxia Liu ◽  
Lina Lu ◽  
Yuqing Xu ◽  
...  

Cyclin-dependent kinase regulatory subunit 2 (CKS2) is a member of the cell cycle-dependent protein kinase subunit family, which is implicated as an oncogene in various malignancies. However, the clinical significance, oncogenic functions, and related mechanisms of CKS2 in hepatocellular carcinoma (HCC) remain largely unclear. In the present study, expression features and prognostic value of CKS2 were evaluated in the bioinformatic databases and HCC tissues. The effects of CKS2 on the malignant phenotypes of HCC cells were explored in vitro. According to the analyses of three bioinformatic databases, mRNA levels of CKS2 were elevated in HCC tissues compared with the normal tissues. Immunohistochemical assays found that high CKS2 expression was closely associated with liver cirrhosis (P=0.019), poor differentiation (P=0.02), portal vein invasion (P<0.001), TNM stage (P=0.019), tumor metastasis (P=0.008), and recurrence (P=0.003). The multivariate regression analyses suggested that CKS2 was an independent prognostic factor for overall survival (HR=2.088, P=0.014) and disease-free survival (HR=2.511, P=0.002) of HCC patients. Moreover, the bioinformatic analyses indicated that CKS2 might be associated with the malignant phenotypes in HCC progression. In addition, in vitro assays showed that CKS2 expression was higher in HCC cell lines than in normal liver cells. Knockdown of CKS2 remarkably repressed the proliferation, colony formation (P=0.0003), chemoresistance, migration (P=0.0047), and invasion (P=0.0012) of HCC cells. Taken together, overexpression of CKS2 was significantly correlated with poor prognosis of HCC patients and the malignant phenotypes of HCC cells, suggesting that it was a novel prognostic biomarker and potential target of HCC.


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