Immunoscore based on PD-L1/PD-1 and CD8+ T cells as prognostic marker for stage II/III gastric cancer.

2017 ◽  
Vol 35 (4_suppl) ◽  
pp. 69-69
Author(s):  
Ti Wen ◽  
Xiujuan Qu ◽  
Yi Li ◽  
Zhi Li ◽  
Xiaofang Che ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
T Cells ◽  
Comprehensive Evaluation ◽  
Hazard Analysis ◽  
Prognostic Significance ◽  
Stage Ii ◽  
Kaplan Meier ◽  
Hazard Ratios ◽  
Tumor Tissues ◽  
Independent Prognostic Significance

69 Background: PD-L1/PD-1 pathway has become an important target in tumor immunotherapy. However, the prognostic value of PD-L1/PD-1 for gastric cancer (GC) remains controversial due to the complexity of immune response. Therefore, comprehensive evaluation of PD-L1/PD-1 expression and CD8+T cells is necessary and superior to one factor in predicting survival. Methods: 166 patients with stage II-III GC were enrolled. Expression of PD-L1, PD-1, and CD8 protein in tumor tissues was examined by IHC staining, and their association with patient’s survival was analyzed by Kaplan-Meier method. Immunoscore classification was constructed using a scoring system, which was based on hazard ratios in a Cox proportional hazard analysis. Results: Expression of PD-L1 was found in 22.29% of immune cells (IC) and 38.55% of tumor cells (TC), while expression of PD-1 was found in 31.33% of IC. CD8High was detected in 41.57% patients. PD-L1+ and PD-1+ IC were both correlated with worse overall survival (OS) ( P=0.0009 and P=0.0004, respectively). In contrast, TC PD-L1+ was associated with better clinical outcomes, including Borrmann classification 0-1, lower AJCC stage, CD8High infiltration and better OS ( P<0.05). Furthermore, IC PD-L1, IC PD-1, CD8, and TC PD-L1 had independent prognostic significance after TNM stage adjustment, and we built an immunoscore system based on these immune factors. Patients with same stage could be further categorized into low-/median-/high-risk subgroups according to their immunoscores. Conclusions: Immunoscore based on comprehensive evaluation of PD-L1/PD-1 and CD8+ T cells can separate GC patients with same stage into different risk subgroups, and might provide suggestion for immunotherapy options in GC.

Bioinformatics Analysis Identifies CPZ as a Tumor Immunology Biomarker For Gastric Cancer

2020 ◽  
Vol 15 ◽  
Author(s):  
Yuan Gu ◽  
Ying Gao ◽  
Xiaodan Tang ◽  
Huizhong Xia ◽  
Kunhe Shi
Keyword(s):  
Gastric Cancer ◽  
T Cells ◽  
Signaling Pathway ◽  
Tumor Immunology ◽  
Bioinformatics Analysis ◽  
Human Cancer ◽  
Disease Free Survival ◽  
Kaplan Meier ◽  
Potential Biomarker ◽  
Pathway Regulation

Background: Gastric cancer (GC) is one of the most common malignancies worldwide. However, the biomarkers for the prognosis and diagnosis of Gastric cancer were still need. Objective: The present study aimed to evaluate whether CPZ could be a potential biomarker for GC. Method: Kaplan-Meier plotter (http://kmplot.com/analysis/) was used to determine the correlation between CPZ expression and overall survival (OS) and disease-free survival (DFS) time in GC [9]. We analyzed CPZ expression in different types of cancer and the correlation of CPZ expression with the abundance of immune infiltrates, including B cells, CD4+ T cells, CD8+ T cells, neutrophils, macrophages, and dendritic cells, via gene modules using TIMER Database. Results: The present study identified that CPZ was overexpressed in multiple types of human cancer, including Gastric cancer. We found that overexpression of CPZ correlates to the poor prognosis of patients with STAD. Furthermore, our analyses show that immune infiltration levels and diverse immune marker sets are correlated with levels of CPZ expression in STAD. Bioinformatics analysis revealed that CPZ was involved in regulating multiple pathways, including PI3K-Akt signaling pathway, cGMP-PKG signaling pathway, Rap1 signaling pathway, TGF-beta signaling pathway, regulation of cell adhesion, extracellular matrix organization, collagen fibril organization, collagen catabolic process. Conclusion: This study for the first time provides useful information to understand the potential roles of CPZ in tumor immunology and validate it to be a potential biomarker for GC.

Amplification and expression of c-MET correlate with poor prognosis of patients with gastric cancer and upregulate the expression of PDL1

2021 ◽  
Vol 53 (5) ◽  
pp. 547-557
Author(s):  
Ya’nan Yang ◽  
Chenchen Wang ◽  
Congqi Dai ◽  
Xinyang Liu ◽  
Wenhua Li ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Prognostic Significance ◽  
Growth Factor Receptor ◽  
Disease Free Survival ◽  
Positive Association ◽  
Her2 Positive ◽  
Kaplan Meier ◽  
Met Amplification ◽  
Amplification Rate ◽  
Cox Proportional Hazard Regression

Abstract The prognostic significance of c-MET in gastric cancer (GC) remains uncertain. In the present study, we examined the amplification, expression, and the prognostic value of c-MET, human epidermal growth factor receptor 2 (HER2), and programmed cell death 1 ligand 1 (PDL1), together with the correlations among them in a large cohort of Chinese samples. A total of 444 patients were included. The immunohistochemistry (IHC) and the dual-color silver in situ hybridization (SISH) were performed to examine their expression and amplification. Univariate and multivariate analyses were performed by the Cox proportional hazard regression model, and survival curves were estimated by the Kaplan–Meier method. The positivity determined by IHC of c-MET was 24.8%, and the MET amplification rate was 2.3%. The positivity rates of HER2 and PDL1 were 8% and 34.7%, respectively. PDL1 expression had a significantly positive association with c-MET expression. c-MET positivity played a significant prognostic role in disease-free survival (DFS) (P = 0.032). Patients with mesenchymal-epithelial transition (MET) amplification had significantly poorer prognosis on both DFS and overall survival (OS). Subgroup analysis showed that in HER2-negative patients, but not in HER2-positive patients, MET-positive patients had significantly worse DFS (P = 0.000) and OS (P = 0.006). c-MET regulated the expression of PDL1 through an AKT-dependent pathway. c-MET inhibitor enhanced the T-cell killing ability and increased the efficacy of PD1 antibody. c-MET was found to be an independent prognostic factor for DFS of GC patients. A combination of c-MET inhibitors and PD1 antibodies could enhance the killing capacity of T cells, providing a preliminary basis for the clinical research on the same combination in GC treatment.

scholarly journals Gastric Cancer Treatments and Survival Trends in the United States

2020 ◽  
Vol 28 (1) ◽  
pp. 138-151
Author(s):  
Kelly A. Stahl ◽  
Elizabeth J. Olecki ◽  
Matthew E. Dixon ◽  
June S. Peng ◽  
Madeline B. Torres ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Overall Survival ◽  
Stage Iv ◽  
The United States ◽  
Current Treatment ◽  
Stage I ◽  
Stage Ii ◽  
Chi Square ◽  
Specific Guideline ◽  
Kaplan Meier

Gastric cancer is the third most common cause of cancer deaths worldwide. Despite evidence-based recommendation for treatment, the current treatment patterns for all stages of gastric cancer remain largely unexplored. This study investigates trends in the treatments and survival of gastric cancer. The National Cancer Database was used to identify gastric adenocarcinoma patients from 2004–2016. Chi-square tests were used to examine subgroup differences between disease stages: Stage I, II/III and IV. Multivariate analyses identified factors associated with the receipt of guideline concordant care. The Kaplan–Meier method was used to assess three-year overall survival. The final cohort included 108,150 patients: 23,584 Stage I, 40,216 Stage II/III, and 44,350 Stage IV. Stage specific guideline concordant care was received in only 73% of patients with Stage I disease and 51% of patients with Stage II/III disease. Patients who received guideline consistent care had significantly improved survival compared to those who did not. Overall, we found only moderate improvement in guideline adherence and three-year overall survival during the 13-year study time period. This study showed underutilization of stage specific guideline concordant care for stage I and II/III disease.

Expression and Clinical Significance of Serum Exosomal miR-375 in Patients with Gastric Cancer

2021 ◽  
Vol 7 (5) ◽  
pp. 3896-3904
Author(s):  
Daoting Deng ◽  
Hong Zhang ◽  
Junxi Liu ◽  
Lina Ma ◽  
Xinrui Lei ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cancer Patients ◽  
Cox Regression ◽  
Prognostic Significance ◽  
Cox Regression Analysis ◽  
Healthy Group ◽  
Cancer Group ◽  
Kaplan Meier ◽  
Gastric Cancer Patients ◽  
Gastric Cancer Group

To explore exosomal miR-375 expression in gastric cancer patients and its relationship with patient prognosis. A total of 53 patients diagnosed with gastric cancer in our hospital from May 2014 to May 2016 were included as the gastric cancer group, and 46 healthy women who came to our hospital for physical examination during the same period were enrolled as the healthy group. Exosomal miR-375 expression level was detected using qRT-PCR, and the diagnostic performance and prognostic significance of exosomal miR-375 in gastric cancer were explored. The gastric cancer group showed increased exosomal miR-375 expression than the healthy group (P< 0.05); Kaplan-Meier survival analysis exhibited that serum exosomal miR-375 has an AUC of 0.778, sensitivity of 69.57%, and specificity of 75.47%, whereas Cox regression analysis showed that the miR-375 expression in exosomes was an independent risk factor affecting the prognosis of gastric cancer patients (P< 0.05). Patient with gastric cancer showed upregulated miR-375 expression in serum exosomes. Serum exosomal miR-375 was found to has positive sensitivity and specificity in the diagnosis of gastric cancer, which may be associated with poor prognosis of gastric cancer patients.

scholarly journals Prognostic significance of natural killer cell-associated markers in gastric cancer: quantitative analysis using multiplex immunohistochemistry

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Hee Young Na ◽  
Yujun Park ◽  
Soo Kyung Nam ◽  
Jiwon Koh ◽  
Yoonjin Kwak ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
T Cells ◽  
B Cells ◽  
Nk Cells ◽  
Natural Killer ◽  
Immune Cells ◽  
Nk Cell ◽  
Critical Role ◽  
Killer Cell ◽  
Prognostic Significance

Abstract Background Natural killer (NK) cells mediate the anti-tumoral immune response as an important component of innate immunity. The aim of this study was to investigate the prognostic significance and functional implication of NK cell-associated surface receptors in gastric cancer (GC) by using multiplex immunohistochemistry (mIHC). Methods We performed an mIHC on tissue microarray slides, including 55 GC tissue samples. A total of 11 antibodies including CD57, NKG2A, CD16, HLA-E, CD3, CD20, CD45, CD68, CK, SMA, and ki-67 were used. CD45 + CD3-CD57 + cells were considered as CD57 + NK cells. Results Among CD45 + immune cells, the proportion of CD57 + NK cell was the lowest (3.8%), whereas that of CD57 + and CD57- T cells (65.5%) was the highest, followed by macrophages (25.4%), and B cells (5.3%). CD57 + NK cells constituted 20% of CD45 + CD57 + immune cells while the remaining 80% were CD57 + T cells. The expression of HLA-E in tumor cells correlated with that in tumoral T cells, B cells, and macrophages, but not CD57 + NK cells. The higher density of tumoral CD57 + NK cells and tumoral CD57 + NKG2A + NK cells was associated with inferior survival. Conclusions Although the number of CD57 + NK cells was lower than that of other immune cells, CD57 + NK cells and CD57 + NKG2A + NK cells were significantly associated with poor outcomes, suggesting that NK cell subsets play a critical role in GC progression. NK cells and their inhibitory receptor, NKG2A, may be potential targets in GC.

Prognostic value of biglycan in gastric cancer

2020 ◽  
Author(s):  
Sizhe Hu ◽  
Peipei Li ◽  
Chenying Wang ◽  
Xiyong Liu
Keyword(s):  
Gastric Cancer ◽  
Transcription Factors ◽  
Poor Prognosis ◽  
Prognostic Significance ◽  
Bioinformatic Analysis ◽  
Gene Set Enrichment Analysis ◽  
High Expression ◽  
Mrna Levels ◽  
Gene Signatures ◽  
Kaplan Meier

Abstract Background: BGN (biglycan) is a family member of small leucine-rich repeat proteoglycans. High expression of BGN might enhance the invasion and metastasis in some types of tumors. Here, the prognostic significance of BGN was evaluated in gastric cancer.Material and Methods: Two independent Gene Expression Omnibus (GEO) gastric cancer microarray datasets( n= 64, n=432) were collected for this study. Kaplan-Meier analysis was applied to evaluate if BGN impacts the outcomes of gastric cancer. The gene set enrichment analysis (GSEA) was used to explore BGN and cancer-related gene signatures. Bioinformatic analysis predicted the putative transcription factors of BGN.Results: For gastric cancer, the mRNA expression level of BGN in tumor tissues was significantly higher than that in normal tissues. Kaplan-Meier analysis showed that higher expression of BGN mRNA was significantly associated with more reduced recurrence-free survival (RFS). GSEA results suggested that BGN significantly enriched metastasis and poor prognosis gene signatures, revealing that BGN might be associated with cell proliferation, poor differentiation, high invasiveness of gastric cancer. Meanwhile, the putative transcription factors, including AR, E2F1, and TCF4, weres predicted by bioinformatic analysis and also significantly correlated with expression of BGN in mRNA levels. Conclusion: High expression of BGN mRNA was significantly related to poor prognosis, which suggested BGN was a potential prognostic biomarker and therapeutic target of gastric cancer.

Use of tumor site as a prognosticator: Population-based analysis of rectosigmoid and rectum cancers

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 4123-4123
Author(s):  
K. P. Raj ◽  
A. Ziogas ◽  
A. R. Barleben ◽  
M. J. Stamos ◽  
J. A. Zell
Keyword(s):  
Large Population ◽  
Prognostic Significance ◽  
Tumor Location ◽  
Population Based ◽  
Stage Ii ◽  
Clinical Factors ◽  
Distal Rectum ◽  
Kaplan Meier ◽  
Rectal Cancers ◽  
Using Data

4123 Background: The study examines the prognostic significance of tumor location exclusively in rectosigmoid and rectal cancers. Although tumor location has traditionally been regarded as a prognostic determinant, data in support of this claim are lacking. We set out to determine this using data from a large population-based California Cancer Registry (CCR). Methods: A retrospective analysis of surgically treated cancer cases involving the rectum and rectosigmoid from 1994–2006 with a follow-up until January 2008 in CCR was conducted. Sub-site tumor location of the cancers involving the rectum was either defined as rectosigmoid or mid/distal rectum. Site-specific survival analyses were conducted by Kaplan-Meier method and hazard ratio calculated using Cox proportional hazard ratios (HR). Results: A total of 33,418 rectal cancer cases were identified, including 12,407 (37.1%) rectosigmoid cancers and 21,011 (62.9%) mid/distal rectum cancers. No significant differences by tumor location were noticed for age, gender, stage, histological type, grade or socioeconomic status. Fewer rectosigmoid cancers received radiation (81.9% vs. 62.3% p=<0.0001)) compared to mid/distal rectum cancers. After adjustment for treatment and relevant clinical factors, an improved rate of CRC-specific survival was noticed in non-metastatic rectosigmoid cancers when compared to cancers involving the mid/distal rectum. A significant decrease in mortality was observed in Stage-I [HR- 0.74(0.63–0.86)], Stage-II [HR-0.76(0.69–0.85)] and Stage-III [HR- 0.90 (0.83–0.98)] rectosigmoid cancers when compared to mid/distal rectum cancers. Number of lymph nodes examined (>12 vs. <12) was an independent prognostic factor for survival in Stage-II patients [HR-0.74 (0.63–0.87)]. Conclusions: Among locoregional cases, rectosigmoid cancers were found to have an improved CRC-specific survival compared to mid/distal rectum cancers, which was independent of other relevant clinical factors. [Table: see text] No significant financial relationships to disclose.

scholarly journals Prognostic Impact of Postoperative Systemic Inflammatory Response in Patients with Stage II/III Gastric Cancer

2021 ◽  
Author(s):  
Kenji Kuroda ◽  
Takahiro Toyokawa ◽  
Yuichiro Miki ◽  
Mami Yoshii ◽  
Tatsuro Tamura ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Inflammatory Response ◽  
Systemic Inflammation ◽  
Early Phase ◽  
Prognostic Significance ◽  
Infectious Complications ◽  
Systemic Inflammatory Response ◽  
Stage Ii ◽  
Prognostic Impact ◽  
Maximum Serum

Abstract Background: Several studies have shown that postoperative infectious complications correlate with poor prognosis in various malignancies, but the prognostic significance of the postoperative inflammatory response in patients with gastric cancer remains unclear. This study examined whether the systemic inflammatory response present in the early phase of the postoperative state correlates with long-term outcomes and to identify markers in patients with stage II/III gastric cancer.Methods: This study retrospectively reviewed 444 consecutive patients who underwent radical gastrectomy for stage II/III gastric cancer. We evaluated maximum serum C-reactive protein (CRPmax) and white blood cell count (WBCmax), defined as the maximum serum CRP level and maximum WBC count during the interval from surgery until discharge, as systemic inflammation markers.Results: In univariate analyses, CRPmax, WBCmax and infectious complications were significantly associated with both overall survival (OS) (p<0.001, p<0.001 and p=0.011, respectively) and relapse-free survival (RFS) (p<0.001, p=0.001 and p<0.001, respectively). Multivariate analysis revealed that high-CRPmax (>9.2 mg/dL) was an independent prognostic factor for OS (hazard ratio (HR) 1.69, 95% confidence interval (CI) 1.18–2.42, p=0.004) and RFS (HR 1.42, 95%CI 1.02–1.98, p=0.038), while WBCmax and infectious complications were not. Conclusion: CRPmax, which reflects the magnitude of systemic inflammation induced by surgical stress and postoperative complications in the early phase after surgery, may be a promising prognostic indicator in patients with stage II/III gastric cancer who undergo curative resection.

scholarly journals Prealbumin and lymphocyte-based prognostic score, a new tool for predicting long-term survival after curative resection of stage II/III gastric cancer

2018 ◽  
Vol 120 (12) ◽  
pp. 1359-1369 ◽  
Author(s):  
Qian Shen ◽  
Wu Liu ◽  
Hu Quan ◽  
Shuguang Pan ◽  
Shuang Li ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Retrospective Study ◽  
Lymphocyte Count ◽  
Prognostic Score ◽  
Locally Advanced ◽  
Prognostic Significance ◽  
Disease Free Survival ◽  
Stage Ii ◽  
Predictive Score ◽  
Term Survival

AbstractThe aim of this retrospective study was to investigate the prognostic significance of pre-treatment immunological and nutritional statuses in patients with locally advanced gastric cancer (GC), and to use the risk factors to develop a predictive score. A total of 731 patients who underwent gastrectomy for stage II/III GC from November 2010 to December 2015 were recruited into this retrospective study. On the basis of univariate and further multivariate Cox regression analyses, decreased pretreatment lymphocyte count (<1·5×109/litre) and prealbumin concentrations (<180 mg/l) were identified to be independently associated with poorer overall survival (OS) and disease-free survival (DFS). Low albumin concentrations (<33 g/l) were identified as an independent risk factor only for OS, but not for DFS. Thereafter, patients who had a decreased prealbumin concentration and lymphocyte count were given a combination of serum prealbumin concentration and lymphocyte count (Co-PaL) score of 2. Patients with only one or neither of these concentrations were given a Co-PaL score of 1 or 0, respectively. Both the OS and the DFS time were inversely related to the Co-PaL scores, and the differences among the three groups were all significant. In contrast, the prognosis did not differ significantly between patients with good nutrition and those with mild to moderate malnutrition according to the prognostic nutritional index. This study indicated that the simple scoring system could accurately predict the prognosis of patients who underwent gastrectomy for stage II/III GC. The score might be helpful in terms of clinical preoperative decision-making.

scholarly journals Characterization of the prognostic values of the NDRG family in gastric cancer

2019 ◽  
Vol 12 ◽  
pp. 175628481985850 ◽  
Author(s):  
Chaoran Yu ◽  
Xiaohui Hao ◽  
Sen Zhang ◽  
Wenjun Hu ◽  
Jianwen Li ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
T Cells ◽  
Poor Prognosis ◽  
Wide Spectrum ◽  
Mitotic Cell ◽  
High Risk Group ◽  
The Cancer Genome Atlas ◽  
Follicular Helper ◽  
Kaplan Meier ◽  
Cancer Genome Atlas

Background: The N-myc downstream-regulated gene ( NDRG) family, NDRG1-4, has been involved in a wide spectrum of biological functions in multiple cancers. However, their prognostic values remain sparse in gastric cancer (GC). Therefore, it is crucial to systematically investigate the prognostic values of the NDRG family in GC. Methods: The prognostic values of the NDRG family were evaluated by Kaplan–Meier Plotter and SurvExpress. The mRNA of the NDRG family was investigated in The Cancer Genome Atlas (TCGA). Transcription factors (TFs) and miRNAs associated with the NDRG family were predicted by NetworkAnalysis. The prognostic values of DNA methylation levels were analyzed by MethSurv. The correlation between immune cells and the NDRG family was evaluated by the Tumor Immune Estimation Resource (TIMER) database. Results: High levels of mRNA expression of NDRG2 and NDRG3 were associated with a favorable prognosis in all GCs. In HER2− GC, NDRG1 was significantly associated with a poor prognosis of GC [hazard ratio (HR) = 1.65, 95% confidence interval (CI) = 1.16–2.33, p = 0.0046]. In HER2+ GC, NDRG4 showed a poor prognosis (HR = 1.4, 95% CI: 1.06–1.85, p = 0.017). NDRG4 was an independent prognostic factor in recurrence-free survival by TCGA cohort. The low-risk NDRG-signature group displayed a significantly favorable survival outcome than the high-risk group (HR = 1.76, 95% CI: 1.2–2.59, p = 0.00385). The phosphorylated protein NDRG1 (NDRG1_pT346) displayed a favorable overall survival and was significantly associated with HER2 and phosphorylated HER2. Epidermis development was the top biological process (BP) for coexpressed genes associated with NDRG1 and NDRG4, while mitotic nuclear division and mitotic cell processes were the top BPs for NDRG2 and NDRG3, respectively. Overall, 6 CpGs of NDRG1, 4 CpGs of NDRG2, 3 CpGs of NDRG3 and 24 CpGs of NDRG4 were associated with significant prognosis. CD4+ T-cells showed the highest correlation with NDRG4 (correlation = 0.341, p = 2.14e−11). Furthermore, BCL6 in follicular helper T-cells (Tfh) cells showed the highest association with NDRG4 (correlation = 0.438, p = 00e+00). Conclusions: This study analyzed the multilevel prognostic values and biological roles of the NDRG family in GC.

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