Tumor purity as a prognosis and immunotherapy relevant feature in gastric cancer

Abstract Background: Few studies have focused on the underlying relationship between the prognosis of tumor mutation burden (TMB) and immune cell infiltration in gastric cancer (GC). This study aims to explore the relationship among TMB and various components in tumor microenvironment (TME). Methods: The transcription profiles and somatic mutation data of 375 tumor and 32 normal samples were obtained from TCGA. The specific mutation information was summarized and visualized with waterfall chart, then number of TMB per million bases of each GC sample was calculated. Immune/stromal scores and tumor purity were calculated by the ‘ESTIMATE’ package, and the fractions of 22 immune cells in each sample were evaluated by CIBERSORT algorithm. Finally, Lass regression analysis was utilized to generate a prognostic scoring signature with TCGA cohort as the training set, while GES84437 cohort as the validation set. Results: Higher TMB indicated favorable overall survival (OS, P = 0.043)，better disease specific survival (P = 0.029), and longer progression free interval (P = 0.004). TMB was positively correlated with MSI and tumor purity, while negatively associated with immune/stromal scores. Moreover, TMBhigh group has lower T cells CD4 memory resting (P < 0.001) and T cells regulatory (P < 0.001), and more T cells CD4 memory activated (P < 0.001) and T cells follicular helper (P = 0.009). More importanly, the infiltration of dendritic cells activated predicted a worse OS, while T cells CD4 memory activated and T cells follicular helper meant a better OS. Finally, a nomogram combined TMB-related signature with clinicopathologic variables can successfully predict the OS with high accuracy and efficiency.Conclusion: TMB can effectively reveal the immune infiltration status in TME of GC, and might serve as a prognostic classifier for individualized treatment of clinical decision-making.

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Biased Influences of Low Tumor Purity on Mutation Detection in Cancer

Frontiers in Molecular Biosciences ◽

10.3389/fmolb.2020.533196 ◽

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.

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A Novel RNA-Binding Protein Signature to Predict Clinical Outcomes and Guide Clinical Therapy in Gastric Cancer

Frontiers in Medicine ◽

10.3389/fmed.2021.670141 ◽

2021 ◽

Vol 8 ◽

Author(s):

Zhigang Qiu ◽

Haitao Jiang ◽

Kun Ju ◽

Xichun Liu

Keyword(s):

Gastric Cancer ◽

High Risk ◽

Clinical Outcomes ◽

Rna Binding ◽

Binding Protein ◽

Rna Binding Protein ◽

Low Risk ◽

Survival Prediction ◽

Clinical Therapy ◽

Tumor Purity

Objective: This study aimed to develop an RNA-binding protein (RBP)-based signature for risk stratification and guiding clinical therapy in gastric cancer.Methods: Based on survival-related RBPs, an RBP-based signature was established by LASSO regression analysis in TCGA dataset. Kaplan–Meier curves were drawn between high- and low-risk groups. The predictive efficacy of this signature was assessed via ROCs at 1-, 3-, and 5-year survival. Its generalizability was verified in an external dataset. Following adjustment with other clinicopathological characteristics, the independency of survival prediction was evaluated via multivariate Cox regression and subgroup analyses. GSEA was utilized in identifying activated pathways in two groups. Stromal score, immune score, tumor purity, and infiltration levels of 22 immune cells were determined in each sample via the ESTIMATE and CIBERSORT algorithms. The sensitivity to chemotherapy drugs was assessed through the GDSC database.Results: Data showed that patients with high risk exhibited unfavorable clinical outcomes than those with low risk. This signature possessed good performance in predicting 1-, 3-, and 5-year survival and can be independently predictive of patients' survival. Calcium, ECM receptor interaction, and focal adhesion were highly enriched in high-risk samples. High-risk samples presented increased stromal and immune scores and reduced tumor purity. Moreover, this signature presented close relationships with immune infiltrations. Low-risk specimens were more sensitive to sorafenib, gefitinib, vinorelbine, and gemcitabine than high-risk specimens.Conclusion: This RBP-based signature may be a promising tool for predicting clinical outcomes and guiding clinical therapy in gastric cancer.

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Ultrastructural Cytochemical Study of Human Gastric Cancer: Observation of AKP ase,ACP ase,G6P ase,TPP ase and CO ase

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100158819 ◽

1990 ◽

Vol 48 (3) ◽

pp. 254-255

Author(s):

Dong Yuming ◽

Yang Guanglin ◽

Du Wei Dong ◽

Xu Ai Liam

Keyword(s):

Gastric Cancer ◽

Gastric Epithelium ◽

Human Gastric Cancer ◽

Electron Microscopic ◽

Cytochemical Study ◽

Electron Microscopic Cytochemistry ◽

Cytochemical Reaction ◽

Set Up ◽

Cancer Tissues ◽

Cytochemical Technique

The activities and distributions of AKPase ,ACPase,G6Pase,TPPase and COase in human normal gastric mucosa and gastric cancer tissues were studied histochemically at light microscopic level. These enzymes are the marker enzymes of cell membrane lysosome endoplasmic reticulum, Golgi apparatus and mitochondrion objectively. On the basis of the research we set up a special ultrastructural cytochemical technique and first researched into gastric cancer domesticly. Ultrastructural cytochemistry is also called electron microscopic cytochemistry. This new technique possesses both the sensitivity of cytochemical reaction andi the high resolution of electron microscope. It is characterized by direct observation,exact localization and the combination morphology with function.The distributions of AKPase,ACPase,G6Pase,TPPase and COase in 14 cases of gastric cancer and 1 case of gastric Denign lesion were studied ultrastructurally. The results showed: 1. normal gastric epithelium had no AKPase reaction. The reaction of ACPase,G6Pase,TPPase and Coase were found in the corresponding organella, which were consistent with their function.

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Ultrastructural Localization Study of Carcinoembryonic Antigen (CEA) in Gastric Cancer: Immunoelectron Microscopic Observation

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100158807 ◽

1990 ◽

Vol 48 (3) ◽

pp. 252-253

Author(s):

Dong Yuming ◽

Yang Guanglin ◽

Wu Jifeng ◽

Chen Xiaolin

Keyword(s):

Gastric Cancer ◽

Intestinal Metaplasia ◽

Cancer Cells ◽

Microscopic Observation ◽

Biological Significance ◽

Ultrastructural Localization ◽

Mucinous Carcinoma ◽

Surface Glycoprotein ◽

Tubular Adenocarcinoma ◽

Pap Method

On the basis of light microscopic observation, the ultrastructural localization of CEA in gastric cancer was studied by immunoelectron microscopic technique. The distribution of CEA in gastric cancer and its biological significance and the mechanism of abnormal distribution of CEA were further discussed.Among 104 surgically resected specimens of gastric cancer with PAP method at light microscopic level, the incidence of CEA(+) was 85.58%. All of mucinous carcinoma exhibited CEA(+). In tubular adenocarcinoma the incidence of CEA(+) showed a tendency to rising with the increase of degree of differentiation. In normal epithelia and intestinal metaplasia CEA was faintly present and was found only in the luminal surface. The CEA staining patterns in cancer cells were of three types--- cytoplasmic, membranous and weak reactive type. The ultrastructural localization of CEA in 14 cases of gastric cancer was studied by immunoelectron microscopic technique.There was a little or no CEA in the microvilli of normal epithelia. In intestinal metaplasia CEA was found on the microvilli of absorptive cells and among the mucus particles of goblet cells. In gastric cancer CEA was also distributed on the lateral and basal surface or even over the entire surface of cancer cells and lost their polarity completely. Many studies had proved that the alterations in surface glycoprotein were characteristic changes of tumor cells. The antigenic determinant of CEA was glycoprotein, so the alterations of tumor-associated surface glycoprotein opened up a new way for the diagnosis of tumors.

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