scholarly journals Phosphoserine phosphatase as a prognostic biomarker in patients with gastric cancer and its potential association with immune cells

2022 ◽  
Vol 22 (1) ◽  
Author(s):  
Ma-Yan Huang ◽  
Xiao-Yun Liu ◽  
Qiong Shao ◽  
Xu Zhang ◽  
Lei Miao ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Immune Cells ◽  
Expression Patterns ◽  
Immunohistochemical Analysis ◽  
Cancer Center ◽  
Phosphoserine Phosphatase ◽  
Kaplan Meier ◽  
Dismal Prognosis ◽  
Tcga Dataset ◽  
Cox Analysis

Abstract Background Because of dismal prognosis in gastric cancer, identifying relevant prognostic factors is necessary. Phosphoserine phosphatase (PSPH) exhibits different expression patterns in many cancers and has been reported to affect the prognosis of patients with cancer. In this study, we examined the prognostic role of metabolic gene PSPH in gastric cancer based on the TCGA dataset and our hospital–based cohort cases. Methods We collected and analysed RNA-seq data of Pan-cancer and gastric cancer in the TCGA dataset and PSPH expression data obtained from immunohistochemical analysis of 243 patients with gastric cancer from Sun Yat-sen University cancer center. Further, Kaplan–Meier survival analysis and Cox analysis were used to assess the effect of PSPH on prognosis. The ESTIMATE and Cibersort algorithms were used to elucidate the relationship between PSPH and the abundance of immune cells using the TCGA dataset. Results We observed that PSPH expression displayed considerably high in gastric cancer and it was significantly associated with inferior prognosis (P = 0.043). Surprisingly, there was a significant relationship between lower immune scores and high expression of PSPH (P < 0.05). Furthermore, patients with a low amount of immune cells exhibited poor prognosis (P = 0.046). The expression of PSPH significantly increased in activated memory CD4 T cells, resting NK cells and M0 macrophages (P = 0.037, < 0.001, and 0.005, respectively). Conclusions This study highlighted that PSPH influences the prognosis of patients with gastric cancer, and this is associated with the infiltration of tumour immune cells, indicating that PSPH may be a new immune-related target for treating gastric cancer.

scholarly journals Overexpressed pseudogene MT1L associated with tumor immune infiltrates and indicates a worse prognosis in BLCA

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Yanpeng Ding ◽  
Nuomin Liu ◽  
Mengge Chen ◽  
Yulian Xu ◽  
Sha Fang ◽  
...  
Keyword(s):  
Immune Cells ◽  
Biological Function ◽  
Prognostic Biomarker ◽  
Poor Survival ◽  
Common Cancer ◽  
Kaplan Meier ◽  
Cox Analysis ◽  
Kaplan Meier Plotter ◽  
Worse Prognosis

Abstract Background BLCA is a common cancer worldwide, and it is both aggressive and fatal. Immunotherapy (ICT) has achieved an excellent curative effect in BLCA; however, only some BLCA patients can benefit from ICT. MT1L is a pseudogene, and a previous study suggested that MT1L can be used as an indicator of prognosis in colorectal cancer. However, the role of MT1L in BLCA has not yet been determined. Methods Data were collected from TCGA, and logistic regression, Kaplan-Meier plotter, and multivariate Cox analysis were performed to demonstrate the correlation between the pseudogene MT1L and the prognosis of BLCA. To identify the association of MT1L with tumor-infiltrating immune cells, TIMER and TISIDB were utilized. Additionally, GSEA was performed to elucidate the potential biological function. Results The expression of MT1L was decreased in BLCA. Additionally, MT1L was positively correlated with immune cells, such as Tregs (ρ = 0.708) and MDSCs (ρ = 0.664). We also confirmed that MT1L is related to typical markers of immune cells, such as PD-1 and CTLA-4. In addition, a high MT1L expression level was associated with the advanced T and N and high grade in BLCA. Increased expression of MT1L was significantly associated with shorter OS times of BLCA patients (p < 0.05). Multivariate Cox analysis revealed that MT1L expression could be an independent prognostic factor in BLCA. Conclusion Collectively, our findings demonstrated that the pseudogene MT1L regulates the immune microenvironment, correlates with poor survival, and is an independent prognostic biomarker in BLCA.

scholarly journals IMMUNOHISTOCHEMICAL EXPRESSION OF HER2 IN ADENOCARCINOMA OF THE STOMACH

2015 ◽  
Vol 52 (2) ◽  
pp. 152-155 ◽  
Author(s):  
Diego Michelon DE CARLI ◽  
Marta Pires da ROCHA ◽  
Luis Carlos Moreira ANTUNES ◽  
Renato Borges FAGUNDES
Keyword(s):  
Gastric Cancer ◽  
Gastric Adenocarcinoma ◽  
Immunohistochemical Analysis ◽  
Anatomical Site ◽  
Her2 Expression ◽  
Immunohistochemical Expression ◽  
Her2 Gene ◽  
Cross Sectional ◽  
Dismal Prognosis ◽  
Location Methods

Background Worldwide, gastric cancer is the fourth cancer in incidence and the second most common cause of cancer death. Gastric cancer is asymptomatic in the early stages and very often diagnosed at advanced stages, determining a dismal prognosis. Expression of the HER2 gene has been identified in about 20% of gastric cancer cases, and its hyper-expression is associated with poor prognosis. Objective To investigate HER2 immunohistochemical expression in gastric adenocarcinoma and its relationship to the histological type and anatomic location. Methods A cross-sectional retrospective study analyzed the immunohistochemical expression of HER2 in a sample of 48 specimens of gastric cancer. Immunohistochemical analysis were performed using avidin-biotin-peroxidase method with C-erb B2 (clone EP1045Y), as a primary antibody (Biocare Medical, USA). Standardized gastric adenocarcinoma‘s HER2 expression criteria has been used in the analysis of samples. Results There were seven cases with reactivity for HER2. Five were of intestinal-type while two cases were of mixed-type in which the expression occurred in the intestinal component. It was identified a significant association of HER2 expression in the intestinal subtype of gastric adenocarcinoma (P=0.003). Regarding the anatomical site, HER2 was positive in only one (16.6%) of the six proximal cases and six (14.28%) of the 42 distal cases (P=0.88). Conclusion HER2 immunoexpression was identified in 14.6% of the samples, and the expression was significantly associated to Lauren’s intestinal subtype.

scholarly journals The Prognostic Landscape of Tumor-Infiltrating Immune Cells and Immune Checkpoints in Glioblastoma

2019 ◽  
Vol 18 ◽  
pp. 153303381986994 ◽  
Author(s):  
Shiman Wu ◽  
Wenli Yang ◽  
Hua Zhang ◽  
Yan Ren ◽  
Ziwei Fang ◽  
...  
Keyword(s):  
Immune Cells ◽  
Immune Checkpoint ◽  
Immunohistochemical Analysis ◽  
Response To Therapy ◽  
Expression Level ◽  
Immune Checkpoints ◽  
Tumor Escape ◽  
Kaplan Meier ◽  
Significant Difference ◽  
Memory Cd4 T Cells

Tumor-infiltrating immune cells are part of a complex microenvironment and associated with improved clinical outcomes in a broad range of tumor types. However, a detailed map for the prognostic landscape of tumor-infiltrating immune cells and immune checkpoint modulators in glioblastoma is still lacking. Here, with the web-accessible resource, The Cancer Immunome Archive, 28 types of both adaptive and innate tumor-infiltrating immune cells were characterized in glioblastoma. Tumors lacking central memory CD4 T cells or natural killer cells were associated with better prognosis in glioblastoma, as verified by immunohistochemical analysis. Moreover, Kaplan-Meier analysis for a total of 71 key immune checkpoint molecules revealed that the expression level of inducible T cell costimulators, tumor necrosis factor superfamily member 14, and UL16 binding protein 1 were negatively correlated with the clinical outcome of patients with glioblastoma. In addition, there was a significant difference between nontumor and glioblastoma samples of several immune checkpoint modulators based on the expression level of their corresponding gene. Collectively, the annotation of tumor-infiltrating immune cells and immune checkpoint modulators in glioblastoma provides a valuable resource for identifying their involvement in tumor escape mechanisms and response to therapy.

Expression patterns of PD-L1 and other immune checkpoint molecules in gastric cancer.

2019 ◽  
Vol 37 (4_suppl) ◽  
pp. 49-49
Author(s):  
Kenichi Nakamura ◽  
Keiichi Hatakeyama ◽  
Tetsuro Toriumi ◽  
Yusuke Koseki ◽  
Yuhei Waki ◽  
...  
Keyword(s):  
Gene Expression ◽  
Gastric Cancer ◽  
Combination Therapy ◽  
Immune Checkpoint ◽  
Expression Patterns ◽  
Immune Checkpoint Molecules ◽  
New Strategy ◽  
Group A ◽  
Tcga Dataset ◽  
Group B

49 Background: Immune checkpoint inhibitors (ICPIs) have provided clinical benefit for various malignancies. A new attempt was recently made to combine PD-1/PD-L1 inhibitors and other ICPIs. In order to establish a new strategy for ICPI combination therapy, we must first understand the expression patterns of PD-L1 and other ICP molecules. To identify possible candidate agents for application in combination therapy with PD-1/PD-L1, we analyzed the expression patterns of ICP molecules in gastric cancer. Methods: Tumor samples were obtained from 278 patients who underwent gastrectomy for gastric cancer from 2014 to 2016, and a comprehensive gene expression analysis using a DNA microarray. We analyzed the TCGA dataset to identify the candidate ICP molecules in relation to PD-L1. The immune landscape was evaluated according to the expression patterns of known immune cell markers reported by Bindea et al. Results: Seven ICP molecules ( PD-L2, IDO1, CD80, ICOS, CTLA4, LAG3 and TIM3) were coexpressed with PD-L1 in the TCGA dataset. In our cohort, all of these molecules were also coexpressed (R > 0.5, P < 0.0001). Using a cluster analysis based on these gene expression profiles, patients were divided into Group A, characterized by the co-overexpression of PD-L1 and other ICP molecules, and Group B, characterized by the underexpression of PD-L1. In Group A, PD-L2 (R = 0.67) and IDO1 (R = 0.61) were particularly strongly associated with the PD-L1 expression. In Group B, elevated expressions of CTLA4 and ICOS were predominantly observed, and these expressions were strongly correlated with each other (R = 0.90). The tumor stage was significantly more advanced in Group B than in Group A (P = 0.02). Accordingly, Group A exhibited a better survival outcome than Group B. The immune landscape of Group A was particularly enriched for Th1, NK CD56dim and activated dendritic cells. Conclusions: PD-L1 and several immune checkpoint molecules tend to be coexpressed in gastric cancer. The combination of PD-L1/-L2 and IDO1 target agents may be a new strategy for treating gastric cancer with PD-L1 overexpression. In contrast, the underexpression of PD-L1 might be an indication for the use of CTLA4- and/or ICOS-directed therapies.

ceRNA network development and tumor-infiltrating immune cell analysis in Hepatocellular Carcinoma

2021 ◽  
Author(s):  
Li Chen ◽  
Weijie Zou ◽  
Lei Zhang ◽  
Huijuan Shi ◽  
Zhi Li ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Immune Cells ◽  
Molecular Mechanisms ◽  
Immune Cell ◽  
Expression Patterns ◽  
Cell Types ◽  
High Morbidity ◽  
Clinical Prognosis ◽  
Cerna Network ◽  
Kaplan Meier

Abstract Background: Hepatocellular carcinoma is among the primary causes of cancer deaths globally. Despite efforts to understand liver cancer, its high morbidity and mortality remain high. Herein, we constructed two nomograms based on ceRNA networks and invading immune cells to describe the molecular mechanisms along with the clinical prognosis of HCC patients.Methods: RNA maps of tumors and normal samples were downloaded from TCGA. HTseq counts and fragments per megapons per thousand bases were read from 421 samples, including 371 tumor samples and 50 normal samples. We established a ceRNA network based on differential gene expression in normal versus tumor subjects. CIBERSORT was employed to differentiate 22 immune cell types according to tumor transcriptomes. Kaplan-Meier along with Cox proportional hazard analyses were employed to determine the prognosis-linked factors. Nomograms were constructed based on prognostic immune cells and ceRNAs. We employed ROC (Receiver operating characteristic) and calibration curve analyses to estimate these nomogram. Results: The difference analysis found 2028 mRNAs, 128 miRNAs, and 136 lncRNAs to be significantly differentially expressed in tumor samples relative to normal samples. We set up a ceRNA network containing 21 protein-coding mRNAs, 12 miRNAs, and 3 lncRNAs. In kaplan-Meier analysis, 21 of the 36 ceRNAs were considered significant. Of the 22 cell types, resting dendritic cell levels were markedly different in tumor samples versus normal controls. Calibration and ROC curve analysis of the ceRNA network, as well as immune-infiltration of tumor showed resultful accuracy (three-year survival AUC: 0.691, five-year survival AUC: 0.700; three-years survival AUC: 0.674, five-year survival AUC: 0.694). Our data suggest that Tregs, CD4 T-cells, mast cells, SNHG1, HMMR and hsa-miR-421 are associated with HCC based on ceRNA-immune cells co-expression patterns. Conclusion: On the basis of ceRNA network modeling and immune cell infiltration analysis, our study offers an effective bioinformatics strategy for studying HCC molecular mechanisms and prognosis.

scholarly journals Immunohistochemical analysis of pRb2/p130, VEGF, EZH2, p53, p16INK4A, p27KIP1, p21WAF1, Ki-67 expression patterns in gastric cancer

2006 ◽  
Vol 210 (1) ◽  
pp. 183-191 ◽  
Author(s):  
Eliseo Mattioli ◽  
Paraskevi Vogiatzi ◽  
Ang Sun ◽  
Giovanni Abbadessa ◽  
Giulia Angeloni ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Expression Patterns ◽  
Immunohistochemical Analysis ◽  
Ki 67

scholarly journals RAI14 Is a Prognostic Biomarker and Correlated With Immune Cell Infiltrates in Gastric Cancer

2020 ◽  
Vol 19 ◽  
pp. 153303382097068
Author(s):  
Yu Xiao ◽  
Hongpan Zhang ◽  
Guobo Du ◽  
Xue Meng ◽  
Tingting Wu ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Immune Cells ◽  
Immune Cell ◽  
Progression Free Survival ◽  
Clinicopathological Parameters ◽  
Marker Genes ◽  
Poor Overall Survival ◽  
Kaplan Meier ◽  
The Impact ◽  
Kaplan Meier Plotter

Objective: To analyze the expression and clinical significance of retinoic acid-induced protein 14 ( RAI14) in gastric cancer and its relationship with immune cell infiltration by mining databases such as Oncomine, TIMER, UALCAN, and Kaplan Meier Plotter. Methods: RAI14 expression in various cancer types was analyzed using the Oncomine and TIMER databases. We used the Kaplan-Meier Plotter and UALCAN databases to evaluate the impact of RAI14 on clinicopathological parameters in gastric cancer. The correlation between RAI14 expression and immune cell invasion was studied using TIMER. TIMER was also used to analyze the correlation between RAI14 expression and marker levels of tumor-infiltrating immune cells. Results: High RAI14 expression in gastric cancer was significantly associated with poor overall survival (OS; hazard ratio [HR] = 1.82, 95% confidence interval [CI] = 1.53–2.15, P < 0.001) and poor progression-free survival (PFS; HR = 2.16, 95% CI = 1.77–2.65, P < 0.001). Furthermore, high RAI14 expression was significantly associated with poor prognosis of patients with stage 2–4 gastric cancer, but not with OS and PFS of stage 1 patients (OS P = 0.17; PFS P = 0.09), and patients with stage N0 PFS had nothing to do (PFS P = 0.238). RAI14 expression was positively correlated with the infiltration levels of monocytes, tumor-associated macrophages, macrophages, neutrophils, and Treg cells in gastric cancer. Besides, RAI14 expression was closely related to various marker genes in immune cells. Conclusion: RAI14 is highly expressed in gastric cancer, and its expression level is correlated with the prognosis of patients with gastric cancer. RAI14 plays also an important role in the recruitment and regulation of infiltrating immune cells and is, thus, expected to become a target for the optimal treatment of gastric cancer.

scholarly journals Overexpressed Pseudogene MT1L Associated with Tumor Immune Infiltrates and Indicates a Worse Prognosis in BLCA

2020 ◽  
Author(s):  
Yanpeng Ding ◽  
Nuomin Liu ◽  
Mengge Chen ◽  
Yulian Xu ◽  
Sha Fang ◽  
...  
Keyword(s):  
Immune Cells ◽  
Poor Survival ◽  
Common Cancer ◽  
Kaplan Meier ◽  
High Stage ◽  
Cox Analysis ◽  
Biologic Function ◽  
Kaplan Meier Plotter ◽  
Worse Prognosis

Abstract Background BLCA is common cancer worldwide, aggressive, and fatal. Immunotherapy (ICT) has achieved an excellent curative effect in BLCA; however, only part of these patients can benefit from ICT treatment. MT1L belongs to pseudogene, and a previous study has suggested that MT1L can be used as an indicator of prognosis in colorectal cancer. However, the role of MT1L in BLCA has not yet been illuminated. Methods Data was collected from TCGA, and logistic regression, Kaplan-Meier Plotter, and multivariate Cox analysis have been performed to demonstrate the correlation between pseudogene MT1L and prognosis in BLCA. To identify the association of MT1L with tumor-infiltrating immune cells, TIMER and TISIDB were utilized. And GSEA was performed to illuminate the potential biologic function. Results The expression of MT1L was decreased in BLCA. And it is positively connected with immune cells, like Tregs(ρ=0.708) and MDSCs(ρ=0.664). We also confirmed that MT1L is related to typical markers of immune cells，like PD-1, CTLA-4. Besides, the high MT1L expression level is related to the high stage of T, N, and the high grade in BLCA and the increased expression of MT1L was significantly associated with the shorter OS of BLCA patients (P<0.05). Multivariate Cox analysis revealed that MT1L expression could be an independent prognostic factor of BLCA. Conclusion Collectively, our findings demonstrated that pseudogene MT1L regulates the immune microenvironment, correlates with poor survival, and serves as an independent prognostic biomarker in BLCA.

scholarly journals Identification of crucial genes of pyrimidine metabolism as biomarkers for gastric cancer prognosis

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Zhengxin Wu ◽  
Jinshui Tan ◽  
Yifan Zhuang ◽  
Mengya Zhong ◽  
Yubo Xiong ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Regression Analysis ◽  
Survival Analysis ◽  
Risk Model ◽  
Cox Regression ◽  
Clinical Samples ◽  
Pyrimidine Metabolism ◽  
Cox Regression Analysis ◽  
Kaplan Meier ◽  
Cox Analysis

Abstract Background Metabolic reprogramming has been reported in various kinds of cancers and is related to clinical prognosis, but the prognostic role of pyrimidine metabolism in gastric cancer (GC) remains unclear. Methods Here, we employed DEG analysis to detect the differentially expressed genes (DEGs) in pyrimidine metabolic signaling pathway and used univariate Cox analysis, Lasso-penalizes Cox regression analysis, Kaplan–Meier survival analysis, univariate and multivariate Cox regression analysis to explore their prognostic roles in GC. The DEGs were experimentally validated in GC cells and clinical samples by quantitative real-time PCR. Results Through DEG analysis, we found NT5E, DPYS and UPP1 these three genes are highly expressed in GC. This conclusion has also been verified in GC cells and clinical samples. A prognostic risk model was established according to these three DEGs by Univariate Cox analysis and Lasso-penalizes Cox regression analysis. Kaplan–Meier survival analysis suggested that patient cohorts with high risk score undertook a lower overall survival rate than those with low risk score. Stratified survival analysis, Univariate and multivariate Cox regression analysis of this model confirmed that it is a reliable and independent clinical factor. Therefore, we made nomograms to visually depict the survival rate of GC patients according to some important clinical factors including our risk model. Conclusion In a word, our research found that pyrimidine metabolism is dysregulated in GC and established a prognostic model of GC based on genes differentially expressed in pyrimidine metabolism.

scholarly journals Comprehensive Analysis of the Prognosis for Chemokine-Like Factor MARVEL Transmembrane Domain-Containing Family in Hepatocellular Carcinoma

2021 ◽  
Author(s):  
Dan Li ◽  
Shenglan Huang ◽  
Liying Sun ◽  
Jianbing Wu
Keyword(s):  
Hepatocellular Carcinoma ◽  
Transmembrane Domain ◽  
Mrna Level ◽  
Family Members ◽  
Tumor Development ◽  
Progression Free Survival ◽  
Kaplan Meier ◽  
Tcga Dataset ◽  
Cox Analysis ◽  
Kaplan Meier Plotter

Abstract Background and Purpose: Chemokine-like factor (CKLF) MARVEL transmembrane domain-containing family (CMTMs), including chemokine-like factor (CKLF) and CMTM1 to CMTM8. All of these genes participate in tumor development and metastasis of hepatocellular carcinoma (HCC). However, prognosis values and the distinct roles of different CMTMs in HCC are still un-clarified.Materials and Methods: To address this issue, the study explored the function of CMTM family members in the prognosis of HCC by TCGA dataset, UALCAN, Kaplan-Meier Plotter, MethSurv, TIMER2.0 databases.Results: The CKLF and CMTM1/3/4/7/8 mRNA expression was obviously elevated in HCC tissues, while CMTM2/5/6 was lowly expressed. Besides, the mRNA level of CMTMs was closely linked to cancer stage, node metastasis status and tumor grades in HCC patients. What’s more, the expression of CMTM2/5 was correlated with favorable overall survival (OS), while high expressions CKLF and CMTM1/7 were associated with poor OS. Simultaneously, low CKLF and CMTM1/4/7 expressions were significantly relevant to better progression-free survival (PFS), while low CMTM5 expression was apparently concerned with worse PFS. In DNA methylation level, 47 CpGs of CMTMs displayed markedly prognostic values. Multivariate cox analysis also revealed that affecting shorter OS outcomes prognostic factors of CKLF and CMTM7 were independent. GSEA results suggested that CKLF and CMTM7 participated in the development and progression of HCC accompanied with multiple biological processes. Furthermore, CMTMs were dramatically associated with tumor immune infiltrating cells (TIICs) (e.g., neutrophils cells), but CMTM8 expression level was no significant correlations with TIICs.Conclusion: This study renders new insight into the prognostic values of CMTM family members in HCC. Overall, our results indicated that CKLF and CMTM7 could be the prognostic biomarkers in HCC patients.

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