scholarly journals Identification and Development of Subtypes with Poor Prognosis in Gastric Cancer Based on Both Hypoxia and Immune Cell Infiltration

2021 ◽  
Vol Volume 14 ◽  
pp. 9379-9399
Author(s):  
Yao Wang ◽  
Jingjing Sun ◽  
Yang Yang ◽  
Sonia Zebaze Dongmo ◽  
Yeben Qian ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Poor Prognosis ◽  
Immune Cell ◽  
Cell Infiltration ◽  
Immune Cell Infiltration

scholarly journals Characteristics of the Immune Cell Infiltration Landscape in Gastric Cancer to Assistant Immunotherapy

2022 ◽  
Vol 12 ◽  
Author(s):  
Chenlu Li ◽  
Jingjing Pan ◽  
Yinyan Jiang ◽  
Yan Yu ◽  
Zhenlin Jin ◽  
...  
Keyword(s):  
Gene Expression ◽  
Gastric Cancer ◽  
Signaling Pathways ◽  
Poor Prognosis ◽  
Immune Cell ◽  
The Cancer Genome Atlas ◽  
Functional Enrichment ◽  
Cell Infiltration ◽  
Immune Cell Infiltration ◽  
Therapeutic Responses

Background: Gastric cancer (GC) was usually associated with poor prognosis and invalid therapeutical response to immunotherapy due to biological heterogeneity. It is urgent to screen reliable indices especially immunotherapy-associated parameters that can predict the therapeutic responses to immunotherapy of GC patients.Methods: Gene expression profile of 854 GC patients were collected from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) datasets (GSE84433) with their corresponding clinical and somatic mutation data. Based on immune cell infiltration (ICI) levels, molecular clustering classification was performed to identify subtypes and ICI scores in GC patients. After functional enrichment analysis of subtypes, we further explored the correlation between ICI scores and Tumor Mutation Burden (TMB) and the significance in clinical immunotherapy response.Results: Three subtypes were identified based on ICI scores with distinct immunological and prognostic characteristics. The ICI-cluster C, associated with better outcomes, was characterized by significantly higher stromal and immune scores, T lymphocytes infiltration and up-regulation of PD-L1. ICI scores were identified through using principal component analysis (PCA) and the low ICI scores were consistent with the increased TMB and the immune-activating signaling pathways. Contrarily, the high-ICI score cluster was involved in the immunosuppressive pathways, such as TGF-beta, MAPK and WNT signaling pathways, which might be responsible for poor prognosis of GC. External immunotherapy and chemotherapy cohorts validated the patients with lower ICI scores exhibited significant therapeutic responses and clinical benefits.Conclusion: This study elucidated that ICI score could sever as an effective prognostic and predictive indicator for immunotherapy in GC. These findings indicated that the systematic assessment of tumor ICI landscapes and identification of ICI scores have crucial clinical implications and facilitate tailoring optimal immunotherapeutic strategies.

Prognostic and predictive value of tumor-infiltrating immune cells in Japanese patients with stage II/III gastric cancer.

2014 ◽  
Vol 32 (3_suppl) ◽  
pp. 46-46
Author(s):  
Sophie Earle ◽  
Toru Aoyama ◽  
Alexander I. Wright ◽  
Darren Treanor ◽  
Yohei Miyagi ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Adjuvant Chemotherapy ◽  
Immune Cells ◽  
Prognostic Markers ◽  
Immune Cell ◽  
Japanese Patients ◽  
Stage Ii ◽  
Cell Infiltration ◽  
Immune Cell Infiltration ◽  
Treatment Interaction

46 Background: Since the ACTS-GC trial, Japanese patients with stage II/III gastric cancer (GC) receive adjuvant S1 chemotherapy. However, selection of patients (pts) by TNM stage does not predict benefit from adjuvant S1 with certainty. Thus, there is an urgent clinical need to identify predictive biomarkers. Increasing evidence suggests tumor immune cell infiltration may be related to GC pts prognosis. We tested the hypothesis that extent and type of immune cell infiltration in GC is related to benefit from adjuvant chemotherapy. Methods: Tissue microarrays from 252 GC resections (109 pts treated by surgery alone (S), 143 pts treated by surgery and adjuvant S1 chemotherapy (SC)) from the Kanagawa Cancer Center Hospital (Yokohama, Japan) were investigated by immunohistochemistry for common leucocytes antigen (CD45), neutrophils (CD66b), macrophages (CD68 and CD163), T-cell subtypes (CD45R0, CD8, CD3), B-cells (CD20) and Treg cells (FOXP3). Staining was quantified as percentage immunoreactivity/area by automated image analysis. Relationship with overall survival was analyzed. A Cox regression model was used to identify independent prognostic markers and treatment interaction effect. Results: The hazard ratio of S1 was 0.694 in this GC cohort which is similar to the results of the ACTS-GC trial. CD45 and CD45R0 were independent prognostic markers in the S group only (CD45 p=0.032, CD45R0 p=0.003). A treatment interaction effect was seen for CD45, CD45R0, and CD68 (p value for test of interaction: CD45 p=0.062, CD45R0 p=0.082, CD68 p=0.057). Survival in the SC group was significantly poorer compared to the S group for CD45>56% or CD68>7% (p<0.05). Conclusions: This is the first study to investigate the relationship between tumor immune cell infiltration at time of surgery and benefit from adjuvant chemotherapy. Our results indicate that GC patients with high intratumoral levels of CD68, CD45, or CD45R0 positive immune cells might not benefit from adjuvant S1 chemotherapy. These findings require validation in a second independent dataset before conducting a prospective study stratifying patients with stage II/III GC based upon extent of CD45, CD45R0, or CD68 immune cell infiltration for adjuvant treatment.

scholarly journals Follistatin-like 1 (FSTL1) is a Prognostic Biomarker and Correlated with Immune Cell Infiltration in Gastric Cancer

2020 ◽  
Author(s):  
Li Li ◽  
Shanshan Huang ◽  
Yangyang Yao ◽  
Jun Chen ◽  
Junhe Li ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Tumor Immunity ◽  
Survival Data ◽  
Immune Cell ◽  
Bioinformatic Analysis ◽  
Cell Infiltration ◽  
Immune Cell Infiltration ◽  
Western Blot Assay ◽  
Immune Infiltration ◽  
Normal Tissues

Abstract Background: Follistatin-like 1 (FSTL1) plays a central role in the progression of tumor and tumor immunity. However, the effect of FSTL1 on the prognosis and immune infiltration of gastric cancer (GC) remains to be elucidated.Method: The expression of FSTL1 data was analyzed in Oncomine and TIMER databases. Analyses of clinical parameters and survival data were conducted by Kaplan-Meier plotter and immunohistochemistry. Western blot assay and real‐time quantitative PCR (RT-qPCR) was using to analyzed protein and mRNA expression, respectively. The correlations between FSTL1 and cancer immune infiltrates was analyzed by Tumor Immune Estimation Resource (TIME), Gene Expression Profiling Interactive Analysis (GEPIA) and LinkedOmics database.Results: The expression of FSTL1 was significantly higher in GC tissues than in normal tissues, and bioinformatic analysis and Immunohistochemistry (IHC) indicated that high FSTL1 expression significantly correlated with poor prognosis in GC. Moreover, FSTL1 was predicted as an independent prognostic factor in GC patients. Bioinformatics analysis results suggested that FSTL1 mainly involved in tumor progression and tumor immunity. And significant correlations were found between FSTL1 expression and immune cell infiltration in GC.Conclusion: The study effectively revealed useful information about FSTL1 expression, prognostic values, potential functional networks and impact of tumor immune infiltration in GC. In summary, FSTL1 can be used as a biomarker for prognosis and evaluating immune cell infiltration in GC.

scholarly journals CXCL5 overexpression predicts a poor prognosis in pancreatic ductal adenocarcinoma and is correlated with immune cell infiltration

2020 ◽  
Vol 11 (9) ◽  
pp. 2371-2381 ◽  
Author(s):  
Ronghua Zhang ◽  
Qiaofei Liu ◽  
Junya Peng ◽  
Mengyi Wang ◽  
Tong Li ◽  
...  
Keyword(s):  
Pancreatic Ductal Adenocarcinoma ◽  
Poor Prognosis ◽  
Immune Cell ◽  
Cell Infiltration ◽  
Ductal Adenocarcinoma ◽  
Immune Cell Infiltration

scholarly journals Down-Regulated CLDN10 Predicts Favorable Prognosis and Correlates With Immune Infiltration in Gastric Cancer

2021 ◽  
Vol 12 ◽  
Author(s):  
XiongHui Rao ◽  
JianLong Jiang ◽  
ZhiHao Liang ◽  
JianBao Zhang ◽  
ZheHong Zhuang ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
T Cell ◽  
Immune Cell ◽  
Gene Set Enrichment Analysis ◽  
Cell Infiltration ◽  
Her2 Status ◽  
Immune Cell Infiltration ◽  
Cell Markers ◽  
Immune Infiltration

Background: CLDN10, an important component of the tight junctions of epithelial cells, plays a crucial role in a variety of tumors. The effect of CLDN10 expression in gastric cancer, however, has yet to be elucidated.Methods: Differential expression of CLDN10 at the mRNA and protein levels was evaluated using Oncomine, ULCAN, HPA and TIMER2.0 databases. Real-time polymerase chain reaction (RT-PCR) was utilized to further verify the expression of CLDN10 in vitro. Correlations between CLDN10 expression and clinical outcomes of gastric cancer were explored by Kaplan-Meier Plotter. Gene set enrichment analysis (GSEA) and protein-protein interaction (PPI) were performed via LinkedOmics and GeneMANIA. The correlations between CLDN10 expression and immune cell infiltration and somatic copy number alternations (SCNA) in gastric cancer were explored by TIMER2.0 and GEPIA2.0.Results: CLDN10 expression was lower in gastric cancer compared to adjacent normal tissues, and associated with better prognosis. CLDN10 also showed significant differences at different T stages, Lauren classification, treatments and HER2 status. PPI and GSEA analysis showed that CLDN10 might be involved in signal transmission, transmembrane transport and metabolism. In some major immune cells, low expression of CLDN10 was associated with increased levels of immune cell infiltration. In addition, it was found that different SCNA status in CLDN10 might affect the level of immune cell infiltration. Furthermore, the expression of CLDN10 was significantly associated with the expression of several immune cell markers, especially B cell markers, follicular helper T cell (Tfh) markers and T cell exhaustion markers.Conclusion: Down-regulated CLDN10 was associated with better overall survival (OS) in gastric cancer. And CLDN10 may serve as a potential prognostic biomarker and correlate to immune infiltration levels in gastric cancer.

scholarly journals Identification of the Immune Cell Infiltration Landscape in Hepatocellular Carcinoma to Predict Prognosis and Guide Immunotherapy

2021 ◽  
Vol 12 ◽  
Author(s):  
Shiyan Yang ◽  
Yajun Cheng ◽  
Xiaolong Wang ◽  
Ping Wei ◽  
Hui Wang ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Poor Prognosis ◽  
Immune Cell ◽  
Principal Component ◽  
Rna Degradation ◽  
Cancer Genome ◽  
The Cancer Genome Atlas ◽  
Cell Infiltration ◽  
Immune Cell Infiltration ◽  
Efficacy Evaluation

Background: Globally, hepatocellular carcinoma (HCC) is the sixth most frequent malignancy with a high incidence and a poor prognosis. Immune cell infiltration (ICI) underlies both the carcinogenesis and immunogenicity of tumors. However, a comprehensive classification system based on the immune features for HCC remains unknown.Methods: The HCC dataset from The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) cohorts was used in this study. The ICI patterns of 571 patients were characterized using two algorithms: the patterns were determined based on the ICI using the ConsensusClusterPlus package, and principal component analysis (PCA) established the ICI scores. Differences in the immune landscape, biological function, and somatic mutations across ICI scores were evaluated and compared, followed by a predictive efficacy evaluation of ICI scores for immunotherapy by the two algorithms and validation using an external immunotherapy cohort.Results: Based on the ICI profile of the HCC patients, three ICI patterns were identified, including three subtypes having different immunological features. Individual ICI scores were determined; the high ICI score subtype was characterized by enhanced activation of immune-related signaling pathways and a significantly high tumor mutation burden (TMB); concomitantly, diminished immunocompetence and enrichment of pathways associated with cell cycle and RNA degradation were found in the low ICI score subtype. Taken together, our results contribute to a better understanding of an active tumor and plausible reasons for its poor prognosis.Conclusion: The present study reveals that ICI scores may serve as valid prognostic biomarkers for immunotherapy in HCC.

scholarly journals INHBA is A Novel Prognostic Biomarker And Correlated With Immune Infiltrates In Gastric Cancer

2021 ◽  
Author(s):  
Weifeng Yu ◽  
Zishao Zhong ◽  
Guihua He ◽  
Wang Zhang ◽  
Zhenhao Ye ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Extracellular Matrix ◽  
Immune Cell ◽  
Prognostic Biomarker ◽  
Curve Analysis ◽  
Cell Infiltration ◽  
Immune Cell Infiltration ◽  
Collagen Formation ◽  
Matrix Organization ◽  
The Impact

Abstract Background: Inhibin subunit beta A (INHBA) is reportedly a potential prognostic biomarker for a variety of cancers. However, its role in gastric cancer (GC) remains elusive. Methods: The expression of INHBA in GC and healthy tissues based on the data obtained from the UCSC Xena database. Logistic regression and Cox regression was performed to explore the correlation between clinical indicators and INHBA expression. Kaplan–Meier curve analysis was performed to assess the impact of INHBA expression on overall survival(OS). In addition, Received operating characteristic curve analysis was implied to clarify the diagnostic role of INHBA in GC. Functional analyses were conducted to explain the potential functions and enrichment pathways for INHBA. TIMER and GEPIA databases were used to calculate the confidence between INHBA and immune cell infiltration in GC. Results: INHBA was upregulated in GC(P < 0.001) and associated with a poor prognosis(P = 0.037). INHBA expression was an independent risk factor for OS(P = 0.004). Additionally, INHBA was a potential diagnostic marker in GC(AUC=0.961) and it was associated with extracellular matrix organization, response to growth factor, and cell-substrate adhesion. Tumor-associated signaling pathways, such as Wnt, Hippo, and p53, were associated with INHBA. Reactome pathways, such as collagen formation and extracellular matrix organization, were significantly enriched. Moreover, high INHBA expression displayed a strong correlation with immune cell infiltration, especially with macrophage infiltration in GC.Conclusions: INHBA could be a potential prognostic biomarker for GC and may drive the abnormal activity of critical cancer-associated pathways, potentially contributing to immune cell infiltration to promote GC development and becoming a new drug target for targeted GC therapies.

scholarly journals C3aR1 Correlates With Immune Cell Infiltration and Serves as Prognostic and Therapeutic Biomarker in Gastric Cancer

2021 ◽  
Author(s):  
weifeng liu ◽  
Zhijie Chu ◽  
Cheng Yang ◽  
Tianbao Yang ◽  
Yanhui Yang ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
T Cell ◽  
Differentially Expressed Genes ◽  
Tumor Tissue ◽  
Immune Cell ◽  
Gene Set Enrichment Analysis ◽  
Differentially Expressed ◽  
Cell Infiltration ◽  
Immune Cell Infiltration ◽  
Expression Levels

Abstract As the fourth most common malignancy worldwide, gastric cancer can lead more than 720 000 patient death every year. Precisely therapeutic intervention can significantly improve patients’ survival status underlying the precise clarification by molecular indexes. Identifying the biomarkers highly associated with disease prognosis will be helpful to guide the clinical therapy. C3ar1 is an essential receptor in the complement system, and participates in various biological processes associated with immunological responses. To identify the crucial roles of C3AR1 in gastric cancer tmorigenesis, we determined the mRNA profile, protein expression levels and the clinicopathological indexes using cBioportal, Kaplan-Meier plotter and the Human Protein Atlas databases. To identify the molecular network in C3AR1-expressed gastric cancer, we obtained the differentially expressed genes using the GEPIA database compared with normal stomach tissues. Furthermore, we analyzed the biological impact of these differentially expressed genes using protein-protein interaction network and gene set enrichment analysis, in which we identified the hub genes and critical pathways influenced by over-expressed C3AR1 in gastric cancer. Finally, we evaluated the correlation between the C3AR1 expression levels and immune cell infiltration levels utilizing the Tumor Immunoassay Resource database. Our results revealed that the higher expression level of C3AR1 can lead higher infiltration of T cell CD8+, T cell CD4+, macrophage, neutrophil, B cell and myeloid dendritic cells into tumor tissue. Moreover, we also found that higher infiltration of macrophage cells into tumor tissue can worsen the survival of patients with gastric cancer, which may be highly associated with the polarization states of macrophages (TAM and M2 status). Our investigation suggest that C3AR1 can be as an efficient diagnostic biomarkers for gastric cancer therapy.

PDGFRB is a potential prognostic biomarker and correlated with immune infiltrates in gastric cancer

2021 ◽  
pp. 1-14
Author(s):  
Baohong Liu ◽  
Xingxing Xiao ◽  
Ziqin Lin ◽  
Yongliang Lou ◽  
Lingling Zhao
Keyword(s):  
Gastric Cancer ◽  
Immune Cell ◽  
Prognostic Biomarker ◽  
Growth Factor Receptor ◽  
Cell Infiltration ◽  
M2 Macrophage ◽  
Immune Cell Infiltration ◽  
Clinicopathologic Characteristics ◽  
Mortality And Morbidity ◽  
Poor Outcomes

Gastric cancer (GC) is a common cancer with high mortality and morbidity rates worldwide. Although medical and surgical treatments have improved, the mechanisms of the progression of GC remain unclear. Platelet-derived growth factor receptor-β (PDGFRB) plays a pivotal role in angiogenesis and tumor cell proliferation and has been suggested as a prognostic marker of cancer. This study aimed to explore the relationship of PDGFRB expression with clinicopathologic characteristics, immune cell infiltration status, and prognosis in GC. In this study, we visualized the expression and prognostic values of PDGFRB in GC using the Oncomine, UALCAN, GEPIA, and Kaplan-Meier Plotter databases. And then we explored the potential relationships between PDGFRB expression and the levels of immune cell infiltration using the TIMER, GEPIA databases and CIBERSORT algorithm. Furthermore, LinkedOmics analysis was performed to explore the functions for PDGFRB. The results showed close correlations between PDGFRB and immune cell infiltration especially M2 Macrophage infiltration in GC. High PDGFRB expression was related to poor outcomes in GC. High PDGFRB expression can negatively affect GC prognosis by promoting angiogenesis and modulating the tumor immune microenvironment. These results strongly suggest that PDGFRB can be used as a prognostic biomarker of GC and provide novel insights into possible immunotherapeutic targets.

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