scholarly journals Biased Influences of Low Tumor Purity on Mutation Detection in Cancer

2020 ◽  
Vol 7 ◽  
Author(s):  
Jun Cheng ◽  
Jun He ◽  
Shanshan Wang ◽  
Zhangxiang Zhao ◽  
Haidan Yan ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cancer Patients ◽  
Rank Correlation ◽  
The Cancer Genome Atlas ◽  
Tumor Purity ◽  
Mutation Profile ◽  
Cancer Genome Atlas ◽  
Genomic Mutation ◽  
Gastric Cancer Patients ◽  
Colorectal Cancer Patients

The non-cancerous components in tumor tissues, e.g., infiltrating stromal cells and immune cells, dilute tumor purity and might confound genomic mutation profile analyses and the identification of pathological biomarkers. It is necessary to systematically evaluate the influence of tumor purity. Here, using public gastric cancer samples from The Cancer Genome Atlas (TCGA), we firstly showed that numbers of mutation, separately called by four algorithms, were significant positively correlated with tumor purities (all p < 0.05, Spearman rank correlation). Similar results were also observed in other nine cancers from TCGA. Notably, the result was further confirmed by six in-house samples from two gastric cancer patients and five in-house samples from two colorectal cancer patients with different tumor purities. Furthermore, the metastasis mechanism of gastric cancer may be incorrectly characterized as numbers of mutation and tumor purities of 248 lymph node metastatic (N + M0) samples were both significantly lower than those of 121 non-metastatic (N0M0) samples (p < 0.05, Wilcoxon rank-sum test). Similar phenomena were also observed that tumor purities could confound the analysis of histological subtypes of cancer and the identification of microsatellite instability status (MSI) in both gastric and colon cancer. Finally, we suggested that the higher tumor purity, such as above 70%, rather than 60%, could be better to meet the requirement of mutation calling. In conclusion, the influence of tumor purity on the genomic mutation profile and pathological analyses should be fully considered in the further study.

scholarly journals Characteristics of Subtypes Within Microsatellite Instability-high Gastric Cancer Based on a Gene Signature Related to Immune Microenvironment Components

2020 ◽  
Author(s):  
Xiaolong Wu ◽  
Xiangyu Gao ◽  
Xiaofang Xing ◽  
Xianzi Wen ◽  
Ziyu Li ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Microsatellite Instability ◽  
Cancer Patients ◽  
Immune Checkpoint ◽  
Differentially Expressed Gene ◽  
The Cancer Genome Atlas ◽  
Immune Microenvironment ◽  
Clinical Prognosis ◽  
Time Signature ◽  
Gastric Cancer Patients

Abstract Background: Gastric cancer patients with microsatellite instability-high (MSI-H) status have a better clinical prognosis and higher response rate to immune checkpoint inhibitors. However, recent studies have suggested that some molecular pathways in MSI-H tumors could affect tumor immune microenvironment (TIME) components, thereby leading to immunotherapy resistance. We aimed to establish subtypes based on the TIME components of MSI-H gastric cancer and analyze the characteristics of each subtype. Methods: Cohorts from the Cancer Genome Atlas, the Asian Cancer Research Group, and Peking University Cancer Hospital were used for this study. CIBERSORT software was used to analyze the TIME components. A set of genes based on the TIME component characteristics, which we named the MSI-TIME signature, was defined using k-means cluster and differentially expressed gene analysis. Results: By using the MSI-TIME signature in the aforementioned cohorts for cluster analysis, the TIME subtypes within MSI-H gastric cancer (MSI-S1, MSI-S2) were established; the differences between the subgroups were reflected in multiple aspects. The MSI-S1 subtype was characterized by a high density of CD8+ T cells, high expression levels of immune checkpoint molecules including PD-L1, PD-L2, CTLA-4, and a high T-cell inflammation level. Patients with the MSI-S1 subtype could also benefit from adjuvant chemotherapy. In contrast, the WNT/β-catenin pathway was enriched in the MSI-S2 subtype. Conclusion: We found that patients with MSI-H gastric cancer showed very different TIME characteristics and could be divided into two subtypes accordingly. These results might benefit MSI-H gastric cancer patients developing individualized treatment strategies in the future.

scholarly journals Reproduction of the Cancer Genome Atlas (TCGA) and Asian Cancer Research Group (ACRG) Gastric Cancer Molecular Classifications and Their Association with Clinicopathological Characteristics and Overall Survival in Moroccan Patients

2021 ◽  
Vol 2021 ◽  
pp. 1-12
Author(s):  
Jean Paul Nshizirungu ◽  
Sanae Bennis ◽  
Ihsane Mellouki ◽  
Mohammed Sekal ◽  
Dafr-Allah Benajah ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cancer Research ◽  
Overall Survival ◽  
Molecular Subtypes ◽  
Clinicopathological Features ◽  
The Cancer Genome Atlas ◽  
Cancer Genome Atlas ◽  
Gastric Cancer Patients ◽  
Genome Atlas ◽  
E Cadherin

Introduction. The Cancer Genome Atlas (TCGA) project and Asian Cancer Research Group (ACRG) recently categorized gastric cancer into molecular subtypes. Nevertheless, these classification systems require high cost and sophisticated molecular technologies, preventing their widespread use in the clinic. This study is aimed to generating molecular subtypes of gastric cancer using techniques available in routine diagnostic practice in a series of Moroccan gastric cancer patients. In addition, we assessed the associations between molecular subtypes, clinicopathological features, and prognosis. Methods. Ninety-seven gastric cancer cases were classified according to TCGA, ACRG, and integrated classifications using a panel of four molecular markers (EBV, MSI, E-cadherin, and p53). HER2 status and PD-L1 expression were also evaluated. These markers were analyzed using immunohistochemistry (E-cadherin, p53, HER2, and PD-L1), in situ hybridization (EBV and HER2 equivocal cases), and multiplex PCR (MSI). Results. Our results showed that the subtypes presented distinct clinicopathological features and prognosis. EBV-positive gastric cancers were found exclusively in male patients. The GS (TCGA classification), MSS/EMT (ACRG classification), and E-cadherin aberrant subtype (integrated classification) presented the Lauren diffuse histology enrichment and tended to be diagnosed at a younger age. The MSI subtype was associated with a better overall survival across all classifications (TCGA, ACRG, and integrated classification). The worst prognosis was observed in the EBV subtype (TCGA and integrated classification) and MSS/EMT subtype (ACRG classification). Discussion/Conclusion. We reported a reproducible and affordable gastric cancer subtyping algorithms that can reproduce the recently recognized TCGA, ACRG, and integrated gastric cancer classifications, using techniques available in routine diagnosis. These simplified classifications can be employed not only for molecular classification but also in predicting the prognosis of gastric cancer patients.

scholarly journals MIR100HG: a credible prognostic biomarker and an oncogenic lncRNA in gastric cancer

2019 ◽  
Vol 39 (4) ◽  
Author(s):  
Jun Li ◽  
Qingfeng Xu ◽  
Wen Wang ◽  
Shaojun Sun
Keyword(s):  
Gastric Cancer ◽  
Cancer Patients ◽  
Prognostic Biomarker ◽  
Human Cancer ◽  
The Cancer Genome Atlas ◽  
Migration And Invasion ◽  
Epithelial Cell Line ◽  
Tissue Samples ◽  
Poor Prognostic Factor ◽  
Gastric Cancer Patients

Abstract The MIR100HG expression was observed to be up-regulated or down-regulated in human cancer tissues depending on tumor types. However, there was no report about the role of MIR100HG in gastric cancer. In our study, we first found levels of MIR100HG expression were increased in gastric cancer cell lines and tissue samples compared with normal gastric epithelial cell line and adjacent normal gastric mucosa tissue samples, respectively. Moreover, high MIR100HG expression was positively associated with clinical stage, tumor invasion, lymph node metastasis, and distant metastasis in gastric cancer patients. Survival analysis showed MIR100HG expression was negative correlated with clinical outcome in gastric cancer patients from The Cancer Genome Atlas (TCGA) database or our study, and high MIR100HG expression served as an independent poor prognostic factor for gastric cancer patient’s overall survival. The study in vitro suggested down-regulation of MIR100HG expression inhibits cell proliferation, migration, and invasion in gastric cancer. In conclusion, MIR100HG is a credible prognostic biomarker and functions as an oncogenic lncRNA in gastric cancer.

scholarly journals The importance of T-lymphocyte subsets on overall survival of colorectal and gastric cancer patients

Medicina ◽  
2007 ◽  
Vol 43 (7) ◽  
pp. 548 ◽  
Author(s):  
Vida Milašienė ◽  
Eugenijus Stratilatovas ◽  
Violeta Norkienė
Keyword(s):  
Colorectal Cancer ◽  
Gastric Cancer ◽  
Overall Survival ◽  
Cancer Patients ◽  
Cellular Immunity ◽  
Lymphocyte Subsets ◽  
Absolute Number ◽  
Stage Iii ◽  
Gastric Cancer Patients ◽  
Colorectal Cancer Patients

The aim of this study was to evaluate the influence of cellular immunity parameters on overall survival of colorectal and gastric cancer patients after surgery. The parameters of cellular immunity (CD3+, CD4+, CD8+, CD20+, and CD16+) were determined by immunofluorescence method. Cox regression analysis showed no impact of the estimated preoperative and postoperative parameters of cellular immunity on overall survival of colorectal cancer patients and similarly of gastric cancer patients in stage II. However, the analysis showed that the survival of colorectal and gastric cancer patients in stage III depended on immunological parameters determined before surgery: CD3+ (P=0.007 and P=0.007, respectively), CD4+ (P=0.021 and P=0.011, respectively), and CD8+ (P=0.047 and P=0.007) counts. Only the survival of colorectal cancer patients depended on natural killer cell number (P=0.009). Kaplan-Meier analysis showed that patients with stage III colorectal and gastric cancer had better survival rates when absolute number of CD3+ lymphocytes, determined before surgery, was greater than 0.8×109/L, CD4+ – greater than 0.25×109/L, CD8+ – greater than 0.3×109/L. Colorectal cancer patient survived longer when the number of natural killer cells CD16+ was more than 0.25×109/L. This study suggests that higher levels of the absolute number of lymphocyte subsets before surgery have a beneficial effect on overall survival of gastric and colorectal cancer patients in stage III.

A novel assessing system for predicting the prognosis of gastric cancer

Epigenomics ◽  
2019 ◽  
Vol 11 (11) ◽  
pp. 1251-1266
Author(s):  
Siheng Lin ◽  
Rui Zhou ◽  
Dongqiang Zeng ◽  
Jiani Wu ◽  
Jianhua Wu ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Tumor Microenvironment ◽  
Gene Expression Omnibus ◽  
The Cancer Genome Atlas ◽  
Diagnostic Tools ◽  
Expression Data ◽  
Protein Coding ◽  
Kaplan Meier ◽  
Cancer Genome Atlas ◽  
Gastric Cancer Patients

Aim: To develop novel diagnostic tools that can predict the prognosis of gastric cancer. Material & methods: Using RNA expression data from The Cancer Genome Atlas and Gene Expression Omnibus, we established protein-coding RNAs-noncoding RNAs-tumor microenvironment type (PNM) scores, which contain signatures of tumor protein coding genes (P), tumor noncoding genes (N) and immune/stroma cells in tumor microenvironment (M) to predict the prognosis of gastric cancer. Results & conclusion: Based on PNM scores, gastric cancer patients were divided into three subgroups and Kaplan–Meier survival curves revealed significant differences among the subgroups (p < 0.001). Our study showed that the PNM scores could be used as a robust predicting tool for the prognosis of gastric cancer.

scholarly journals Preoperative Use of PET/CT in Patients With Colorectal and Gastric Cancer and Its Impact on Treatment Decision Making

2016 ◽  
Vol 101 (7-8) ◽  
pp. 318-327 ◽  
Author(s):  
Ali E. Atici ◽  
Tebessum Cakir ◽  
Enver Reyhan ◽  
Mustafa Duman ◽  
Ilter Ozer ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Gastric Cancer ◽  
Computed Tomography ◽  
Decision Making ◽  
Cancer Patients ◽  
Treatment Decision ◽  
Treatment Decision Making ◽  
Pet Ct ◽  
Gastric Cancer Patients ◽  
Colorectal Cancer Patients

The advantages of primary positron emission tomography–computed tomography (PET-CT) evaluation of both cancers needs to be clarified. This study aimed to investigate the efficacy of PET-CT compared with computed tomography (CT) in preoperative evaluation of colorectal and gastric cancer patients, and to determine its effects on treatment decision-making. We prospectively evaluated patients who presented with both types of cancer in our clinic between September 2008 and June 2010, using PET-CT and CT. We compared the results with histopathologic findings and determined the changing treatment strategies. In detecting local lymph node positivity, for colorectal cancer patients the sensitivity of PET-CT was 30% and that of CT was 20%; the specificities were the same (100%). For gastric cancer patients, the sensitivity of PET-CT was 38.9% and that of CT was 22%; the specificities were 100% and 83%, respectively. In detecting metastasis, for colorectal cancer patients the sensitivity of PET-CT was 80% and that of CT was 50%; the specificities were similar (100% versus 95%). For gastric cancer patients, the sensitivity of PET-CT was 72% and that of CT was 34%; the specificities were similar (95% versus 90%). In detecting liver metastasis, for colorectal cancer patients the sensitivity of PET was 75% and that of CT was 50%; the specificities were similar (100% versus 95%). For gastric cancer patients, the sensitivity of PET-CT was 57% and that of CT was 28%; the specificities were similar (95% versus 91%). PET-CT findings altered treatment decisions in 16% of patients (n = 10; 9 gastric cancer and 1 colorectal cancer). A high rate of treatment strategy alteration in gastric cancers was seen with PET-CT; its usage is preferred in colorectal cancer staging only for high-risk patients and those with equivocal findings.

scholarly journals Change of the growth hormone–insulin-like growth factor-I axis in patients with gastrointestinal cancer: related to tumour type and nutritional status

2005 ◽  
Vol 93 (6) ◽  
pp. 853-858 ◽  
Author(s):  
Qi Huang ◽  
Yong-Jun Nai ◽  
Zhi-Wei Jiang ◽  
Jie-Shou Li
Keyword(s):  
Colorectal Cancer ◽  
Gastric Cancer ◽  
Growth Hormone ◽  
Growth Factor ◽  
Cancer Patients ◽  
Factor I ◽  
Igf I ◽  
Gastric Cancer Patients ◽  
Colorectal Cancer Patients ◽  
Gh Resistance

Changes in the growth hormone (GH)–insulin-like growth factor-I (IGF-I) axis, especially acquired GH resistance, develop in many severe illnesses, including cachexia. To study changes in the GH–IGF-I axis in patients with cancer cachexia, biochemical markers and body composition parameters were measured in eighty-eight gastric cancer patients, thirty colorectal cancer patients (subclassified according to the presence or absence of cachexia) and twenty-four healthy control subjects. Fifty-nine patients were defined as cachectic, based on the percentage of weight loss compared with their previous normal weight. The remaining fifty-nine patients were defined as non-cachectic. Measurements were repeated in twenty-seven patients (sixteen with gastric cancer and eleven with colorectal cancer) 3 months after radical operation. Compared with the controls, the cachectic gastric cancer patients had high GH levels (1·36 v. 0·32 ng/ml; P=0·001), a trend towards high IGF-I levels (223·74 v. 195·15 ng/ml; P=0·128 compared with non-cachectic patients) and a low log IGF-I/GH ratio (2·55 and 2·66 v. 3·00; P=0·002), along with a decreased BMI; the cachectic colorectal cancer patients showed the biochemical characteristics of acquired GH resistance: high GH (0·71 v. 0·32 ng/ml; P=0·016), a trend towards decreased IGF-I levels (164·18 v. 183·24 ng/ml; P=0·127) and a low log IGF-I/GH ratio (2·54 v. 2·99; P=0·005), with increased IGF-I levels following radical surgery (200·49 v. 141·91 ng/ml; P=0·046). These findings suggest that normal GH reaction and sensitivity occur in gastric cancer patients, controlled by nutritional status, whereas acquired GH resistance develops in cachectic colorectal cancer patients, which may be caused by tumour itself.

scholarly journals Cancer Stem Cell Marker DCLK1 Correlates with Tumorigenic Immune Infiltrates in the Colon and Gastric Adenocarcinoma Microenvironments

Cancers ◽  
2020 ◽  
Vol 12 (2) ◽  
pp. 274 ◽  
Author(s):  
Xiangyan Wu ◽  
Dongfeng Qu ◽  
Nathaniel Weygant ◽  
Jun Peng ◽  
Courtney W. Houchen
Keyword(s):  
Gastric Cancer ◽  
Cancer Patients ◽  
Clinical Outcomes ◽  
Immune Cell ◽  
Prognostic Biomarker ◽  
Unmet Need ◽  
The Cancer Genome Atlas ◽  
Stem Cell Marker ◽  
Sequencing Data ◽  
Gastric Cancer Patients

Immunotherapy that has proven efficacy in several solid cancers plays a partial role in improving clinical outcomes of advanced gastrointestinal (GI) cancers. There is an unmet need to find new immune-related therapeutic targets. Doublecortin-like kinase 1 (DCLK1) marks tuft cells which are recognized as cancer-initiating cells and regulators of the type II immune response, and has been studied for its role in many cancers including colon and gastric cancers, but its role in tumor immunity remains unexplored. In the current study, we analyzed colon and gastric cancer RNA sequencing data from 283 and 415 patients, respectively, from The Cancer Genome Atlas (TCGA). High DCLK1 expression predicted the worse clinical outcomes in colon and gastric cancer patients and correlated with increased immune and stromal components. Further analysis indicated that DCLK1 was strongly linked to infiltration of multiple immune cell types, especially TAMs and Treg, and strongly correlated with increased CD8+ T cell inhibitors TGFB1 and CXCL12 and their receptors, suggesting it may contribute to TAM-mediated inhibition of CD8+ T cells. Interestingly, we found that DCLK1 was a prognostic biomarker in left-sided colon cancer, which has worse outcomes and demonstrates a reduced response to existing immunotherapies. In conclusion, our results demonstrate that DCLK1 is linked with functional regulation of the tumor microenvironment and may have potential as a prognostic biomarker and adjuvant target to promote immunotherapy sensitivity in colon and gastric cancer patients.

scholarly journals New Concept Air Conditioning System for the Operating Room to Minimize Patient Cooling and Surgeon Heating: A Historical Control Cohort Study

2019 ◽  
Vol 44 (1) ◽  
pp. 45-52
Author(s):  
Hisashi Usuki ◽  
Hiroaki Kitamura ◽  
Yasuhisa Ando ◽  
Hironobu Suto ◽  
Eisuke Asano ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Gastric Cancer ◽  
Laparoscopic Surgery ◽  
Cancer Patients ◽  
Air Conditioning ◽  
Air Conditioning System ◽  
Intraoperative Hypothermia ◽  
Gastric Cancer Patients ◽  
Colorectal Cancer Patients ◽  
New System

Abstract Background Intraoperative hypothermia is a common adverse event. For avoiding the complication due to hypothermia, many warming devices and methods have been used in perioperative period. It has been reported that more patients undergoing laparoscopic surgery tend to have hypothermia than with open surgery. To avoid intraoperative hypothermia, many kinds of warming tools have been used. But, it was also reported that some warming methods increased perceptions of distraction and physical demand. Methods To achieve both patients’ normothermia and surgeons’ comfort, new air conditioning (AC) system was designed with considering the characteristics of laparoscopic surgery. The temperature of the airflows to the patient and to the surgeons can be adjusted independently in this new system. The new system has two parts. One controls the temperature of the central area over the operation table. The air from this part falls on the patients. The other part is the lateral area beside the operating table; the air from this part falls on the surgeons. The subjects of this study were 160 gastric cancer patients and 316 colorectal cancer patients undergoing laparoscopic surgery. The temperature of the central flow was set 23.5 °C, and the temperature of the lateral flow was set 22 °C just after the anesthesia. The number of timepoints the patient spent in hypothermic state, defined as a temperature cooler by 0.5 °C or more than that at the starting point of surgery, was determined in each patient. Results In the results, the rate of hypothermic state in old operation rooms was 23.8% and that in new operation rooms was 2.7% in male gastric cancer patients (p < 0.01). And those were 37.1% in old operation rooms and 0.9% in new operation rooms in female gastric cancer patients (p < 0.01). The rate of hypothermic state in old operation rooms was 30.0% and that in new operation rooms was 9.5% in male colorectal cancer patients (p < 0.01). And those were 41.6% in old operation rooms and 8.9% in new operation rooms in female colorectal cancer patients (p < 0.01). The similar results were showed in the study, which subjects were limited the patients undergoing surgery in 2015 and 2016; which were the last year the old operation rooms were used and the first year the new operation rooms were used. Conclusions Thus, the usefulness of the new air conditioning system for achieving both patients’ normothermia and comfort of surgeons could be verified in this study.

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