A novel necroptosis-related gene index for predicting prognosis and a cold tumor immune microenvironment in stomach adenocarcinoma

Khan, Muhammad; Lin, Jie; Wang, Baiyao; Chen, Chengcong; Huang, Zhong; Tian, Yunhong; Yuan, Yawei; Bu, Junguo

doi:10.3389/fimmu.2022.968165

Cited by 24 publications

(18 citation statements)

References 134 publications

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“…Khan et al. ( 57 ) established the necroptosis-related genes prognostic index (NRGPI). They divided gastric cancer patients into high-risk and low-risk subgroups.…”

Section: Discussionmentioning

confidence: 99%

GPX3 expression was down-regulated but positively correlated with poor outcome in human cancers

Chen²,

Yang³

et al. 2023

Front. Oncol.

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IntroductionCancer is a crucial public health problem and one of the leading causes of death worldwide. Previous studies have suggested that GPX3 may be involved in cancer metastasis and chemotherapy resistance. However, how GPX3 affects cancer patients’ outcomes and the underlying mechanism remains unclear.MethodsSequencing data and clinical data from TCGA, GTEx, HPA, and CPTAC were used to explore the relationship between GPX3 expression and clinical features. Immunoinfiltration scores were used to assess the relationship between GPX3 and the tumor immune microenvironment. Functional enrichment analysis was used to predict the role of GPX3 in tumors. Gene mutation frequency, methylation level, and histone modification were used to predict the GPX3 expression regulation method. Breast, ovarian, colon, and gastric cancer cells were used to investigate the relationship between GPX3 expression and cancer cell metastasis, proliferation, and chemotherapy sensitivity.ResultsGPX3 is down-regulated in various tumor tissues, and GPX3 expression level can be used as a marker for cancer diagnosis. However, GPX3 expression is associated with higher stage and lymph node metastasis, as well as poorer prognosis. GPX3 is closely related to thyroid function and antioxidant function, and its expression may be regulated by epigenetic inheritance such as methylation modification or histone modification. In vitro experiments, GPX3 expression is associated with cancer cell sensitivity to oxidant and platinum-based chemotherapy and is involved in tumor metastasis in oxidative environments.DiscussionWe explored the relationship between GPX3 and clinical features, immune infiltration characteristics, migration and metastasis, and chemotherapy sensitivities of human cancers. We further investigated the potential genetic and epigenetic regulation of GPX3 in cancer. Our results suggested that GPX3 plays a complicated role in the tumor microenvironment, simultaneously promoting metastasis and chemotherapy resistance in human cancers.

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“…Khan et al. ( 57 ) established the necroptosis-related genes prognostic index (NRGPI). They divided gastric cancer patients into high-risk and low-risk subgroups.…”

Section: Discussionmentioning

confidence: 99%

GPX3 expression was down-regulated but positively correlated with poor outcome in human cancers

Chen²,

Yang³

et al. 2023

Front. Oncol.

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“…Among all the signatures, StepCox [backward] + Enet [alpha = 0.7] showed the highest average C-index value (0.726). This signature, named in this study as IRS, is composed of 24 genes: TNFAIP2 39 , 40 , SLC37A2 , RGS1 41 , ZNF101 , TM6SF1 , CRHBP , AKAP5 42 , CRYBB1 , S100Z 43 , ACSM5 , NTAN1 44 , IL5RA , ABCG1 , CAMK4 , MCEMP1 45 – 47 , SLC2A3 48 – 50 , RENBP , BASP1 51 , 52 , KYNU 53 , 54 , CTLA4 55 , FCGR2B 56 , ENTPD8 , DDO , FCN1 57 . All of these genes have been mentioned in previous studies to affect the prognosis of patients with GC.…”

Section: Discussionmentioning

confidence: 99%

Use of machine learning-based integration to develop an immune-related signature for improving prognosis in patients with gastric cancer

Ning

Sun

Fan

et al. 2023

Sci Rep

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Gastric cancer is one of the most common malignancies. Although some patients benefit from immunotherapy, the majority of patients have unsatisfactory immunotherapy outcomes, and the clinical significance of immune-related genes in gastric cancer remains unknown. We used the single-sample gene set enrichment analysis (ssGSEA) method to evaluate the immune cell content of gastric cancer patients from TCGA and clustered patients based on immune cell scores. The Weighted Correlation Network Analysis (WGCNA) algorithm was used to identify immune subtype-related genes. The patients in TCGA were randomly divided into test 1 and test 2 in a 1:1 ratio, and a machine learning integration process was used to determine the best prognostic signatures in the total cohort. The signatures were then validated in the test 1 and the test 2 cohort. Based on a literature search, we selected 93 previously published prognostic signatures for gastric cancer and compared them with our prognostic signatures. At the single-cell level, the algorithms "Seurat," "SCEVAN", "scissor", and "Cellchat" were used to demonstrate the cell communication disturbance of high-risk cells. WGCNA and univariate Cox regression analysis identified 52 prognosis-related genes, which were subjected to 98 machine-learning integration processes. A prognostic signature consisting of 24 genes was identified using the StepCox[backward] and Enet[alpha = 0.7] machine learning algorithms. This signature demonstrated the best prognostic performance in the overall, test1 and test2 cohort, and outperformed 93 previously published prognostic signatures. Interaction perturbations in cellular communication of high-risk T cells were identified at the single-cell level, which may promote disease progression in patients with gastric cancer. We developed an immune-related prognostic signature with reliable validity and high accuracy for clinical use for predicting the prognosis of patients with gastric cancer.

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“…APOD is a potential biomarker of hypoxia and is involved in immune responses ( 20 ). APOD is included in a novel necrosis-related gene model for predicting the prognosis of gastric adenocarcinoma and is closely associated with the immune microenvironment of cold tumors ( 21 ). In glioma, POSTN may regulate resistance to anti-VEGF-A therapy by upregulating the expression of TGFβ1 and HIF1α ( 22 ).…”

Section: Discussionmentioning

confidence: 99%

Construction of a hypoxia-immune-related prognostic panel based on integrated single-cell and bulk RNA sequencing analyses in gastric cancer

Deng

Chu

et al. 2023

Front. Immunol.

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IntroductionGastric cancer (GC) is the fifth most common tumor, contributing to the third-highest number of cancer-related deaths. Hypoxia is a major feature of the tumor microenvironment. This study aimed to explore the influence of hypoxia in GC and establish a hypoxia-related prognostic panel.MethodsThe GC scRNA-seq data and bulk RNA-seq data were downloaded from the GEO and TCGA databases, respectively. AddModuleScore() and AUCell() were used to calculate module scores and fractions of enrichment for hypoxia-related gene expression in single cells. Least absolute shrinkage and selection operator cox (LASSO-COX) regression analysis was utilized to build a prognostic panel, and hub RNAs were validated by qPCR. The CIBERSORT algorithm was adopted to evaluate immune infiltration. The finding of immune infiltration was validated by a dual immunohistochemistry staining. The TIDE score, TIS score and ESTIMATE were used to evaluate the immunotherapy predictive efficacy.ResultsHypoxia-related scores were the highest in fibroblasts, and 166 differentially expressed genes were identified. Five hypoxia-related genes were incorporated into the hypoxia-related prognostic panel. 4 hypoxia-related genes (including POSTN, BMP4, MXRA5 and LBH) were significantly upregulated in clinical GC samples compared with the normal group, while APOD expression decreased in GC samples. Similar results were found between cancer-associated fibroblasts (CAFs) and normal fibroblasts (NFs). A high hypoxia score was associated with advanced grade, TNM stage, N stage, and poorer prognosis. Decreased antitumor immune cells and increased cancer-promoting immune cells were found in patients with high hypoxia scores. Dual immunohistochemistry staining showed high expression of CD8 and ACTA2 in gastric cancer tissue. In addition, the high hypoxia score group possessed higher TIDE scores, indicating poor immunotherapy benefit. A high hypoxia score was also firmly related to sensitivity to chemotherapeutic drugs.DiscussionThis hypoxia-related prognostic panel may be effective in predicting the clinical prognosis, immune infiltrations, immunotherapy, and chemotherapy in GC.

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A novel necroptosis-related gene index for predicting prognosis and a cold tumor immune microenvironment in stomach adenocarcinoma

Cited by 24 publications

References 134 publications

GPX3 expression was down-regulated but positively correlated with poor outcome in human cancers

GPX3 expression was down-regulated but positively correlated with poor outcome in human cancers

Use of machine learning-based integration to develop an immune-related signature for improving prognosis in patients with gastric cancer

Construction of a hypoxia-immune-related prognostic panel based on integrated single-cell and bulk RNA sequencing analyses in gastric cancer

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