Identification of molecular features correlating with tumor immunity in gastric cancer by multi-omics data analysis

Yin, Hanlin; Wang, Xiaosheng

doi:10.21037/atm-20-922

Cited by 37 publications

(27 citation statements)

References 57 publications

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“…By interfering with AC006033.2, we found that the proliferation, migration, and invasion of osteosarcoma cell lines were enhanced. Studies have shown that AC006033.2 is also an effective biomarker for anti-tumor immunity in gastric cancer (He and Wang, 2020), which is similar to the results of our study. We found that IRLs signature is closely related to the TIM of osteosarcoma.…”

Section: Discussionsupporting

confidence: 92%

Immune-Related LncRNAs Affect the Prognosis of Osteosarcoma, Which Are Related to the Tumor Immune Microenvironment

Huang

Lin

Chen

et al. 2021

Front. Cell Dev. Biol.

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Background: Abnormal expression of lncRNA is closely related to the occurrence and metastasis of osteosarcoma. The tumor immune microenvironment (TIM) is considered to be an important factor affecting the prognosis and treatment of osteosarcoma. This study aims to explore the effect of immune-related lncRNAs (IRLs) on the prognosis of osteosarcoma and its relationship with the TIM.Methods: Ninety-five osteosarcoma samples from the TARGET database were included. Iterative LASSO regression and multivariate Cox regression analysis were used to screen the IRLs signature with the optimal AUC. The predict function was used to calculate the risk score and divide osteosarcoma into a high-risk group and low-risk group based on the optimal cut-off value of the risk score. The lncRNAs in IRLs signature that affect metastasis were screened for in vitro validation. Single sample gene set enrichment analysis (ssGSEA) and ESTIMATE algorithms were used to evaluate the role of TIM in the influence of IRLs on osteosarcoma prognosis.Results: Ten IRLs constituted the IRLs signature, with an AUC of 0.96. The recurrence and metastasis rates of osteosarcoma in the high-risk group were higher than those in the low-risk group. In vitro experiments showed that knockdown of lncRNA (AC006033.2) could increase the proliferation, migration, and invasion of osteosarcoma. ssGSEA and ESTIMATE results showed that the immune cell content and immune score in the low-risk group were generally higher than those in the high-risk group. In addition, the expression levels of immune escape-related genes were higher in the high-risk group.Conclusion: The IRLs signature is a reliable biomarker for the prognosis of osteosarcoma, and they alter the prognosis of osteosarcoma. In addition, IRLs signature and patient prognosis may be related to TIM in osteosarcoma. The higher the content of immune cells in the TIM of osteosarcoma, the lower the risk score of patients and the better the prognosis. The higher the expression of immune escape-related genes, the lower the risk score of patients and the better the prognosis.

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Section: Discussionsupporting

confidence: 92%

Immune-Related LncRNAs Affect the Prognosis of Osteosarcoma, Which Are Related to the Tumor Immune Microenvironment

Huang

Lin

Chen

et al. 2021

Front. Cell Dev. Biol.

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“…Taking together our results and background literature is possible to correlate LINC01871 with a cytotoxic immune response. Our enrichment analysis showed an association with Interferon alpha and gamma, which are strongly related to cytotoxic response, going in line with what was observed in other studies (44,46). In BRCA, CD8+ T cells are reported as prognostic significance in estrogen receptor (ER)-negative BRCA, but not in ER-positive cases, being associated with better clinical outcomes survival and response to treatment (47).…”

Section: Discussionsupporting

confidence: 91%

“…The authors suggested that this lncRNA may play an important role, mainly related to the above immune processes and immune genes (44). In cervical cancer, LINC01871 was also found in an immune-related prognostic signature being related to immune response and TGF-b signaling pathway (45); additionally, in gastric cancer, LINC01871 expression was positively correlated with CD8+ T cell enrichment levels, cytolytic immune activity, and CD274 (PD-L1) expression levels in TCGA gastric cancer cohort (46).…”

Section: Discussionmentioning

confidence: 99%

Unraveling Immune-Related lncRNAs in Breast Cancer Molecular Subtypes

et al. 2021

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Breast cancer (BRCA) is the most leading cause of cancer worldwide. It is a heterogeneous disease with at least five molecular subtypes including luminal A, luminal B, basal-like, HER2-enriched, and normal-like. These five molecular subtypes are usually stratified according to their mRNA profile patterns; however, ncRNAs are increasingly being used for this purpose. Among the ncRNAs class, the long non-coding RNAs (lncRNAs) are molecules with more than 200 nucleotides with versatile regulatory roles; and high tissue-specific expression profiles. The heterogeneity of BRCA can also be reflected regarding tumor microenvironment immune cells composition, which can directly impact a patient’s prognosis and therapy response. Using BRCA immunogenomics data from a previous study, we propose here a bioinformatics approach to include lncRNAs complexity in BRCA molecular and immune subtype. RNA-seq data from The Cancer Genome Atlas (TCGA) BRCA cohort was analyzed, and signal-to-noise ratio metrics were applied to create these subtype-specific signatures. Five immune-related signatures were generated with approximately ten specific lncRNAs, which were then functionally analyzed using GSEA enrichment and survival analysis. We highlighted here some lncRNAs in each subtype. LINC01871 is related to immune response activation and favorable overall survival in basal-like samples; EBLN3P is related to immune response suppression and progression in luminal B, MEG3, XXYLT1-AS2, and LINC02613 were related with immune response activation in luminal A, HER2-enriched and normal-like subtypes, respectively. In this way, we emphasize the need to know better the role of lncRNAs as regulators of immune response to provide new perspectives regarding diagnosis, prognosis and therapeutical targets in BRCA molecular subtypes.

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“…Loss of ARID1A was found to have a significant correlation with the expression of IFN-g and checkpoint genes (including PD-L1, CTLA4, and PDCD1) in microsatellite-stable colorectal cancer (29). In addition, ARID1A has been proven to serve as a biomarker for the sensitivity to immune checkpoint inhibitors (29)(30)(31)(32).…”

Section: Discussionmentioning

confidence: 99%

ARID1A Downregulation Predicts High PD-L1 Expression and Worse Clinical Outcome in Patients With Gallbladder Cancer

Nan

Wang

et al. 2022

Front. Oncol.

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BackgroundRecent studies have confirmed that AT-rich interactive domain-containing protein 1A (ARID1A) plays a critical role in tumorigenesis, but its role in gallbladder cancer (GBC) remains unclear.MethodsIn total, 224 patients from Zhongshan Hospital were recruited for this retrospective study. The clinicopathological and baseline characteristics of the patients were collected. Bioinformatics analysis was performed to reveal variations in genes and signaling pathways, and ARID1A and PD-L1 expression and the number of PD1+ tumor-infiltrating lymphocytes (TILs) were measured by immunohistochemical staining.ResultsARID1A expression was negatively correlated with overall survival in patients with GBC, and multivariate analysis identified ARID1A as an independent prognostic factor for overall survival. A heatmap and gene set enrichment analysis suggested that cytotoxic T lymphocyte signatures and immune-related signaling pathways were downregulated in ARID1A low tumors. Subsequent immunohistochemical staining confirmed that ARID1A expression was negatively correlated with PD-L1 expression and PD1+ TILs in the tumor microenvironment. The Kaplan–Meier analysis suggested that high ARID1A expression combined with low PD-L1 expression or low PD1+ TIL counts is associated with the best prognosis in patients with GBC.ConclusionARID1A inactivation can lead to a worse prognosis in patients with GBC, potentially by mediating immune evasion through the PD1/PD-L1 pathway.

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Identification of molecular features correlating with tumor immunity in gastric cancer by multi-omics data analysis

Cited by 37 publications

References 57 publications

Immune-Related LncRNAs Affect the Prognosis of Osteosarcoma, Which Are Related to the Tumor Immune Microenvironment

Immune-Related LncRNAs Affect the Prognosis of Osteosarcoma, Which Are Related to the Tumor Immune Microenvironment

Unraveling Immune-Related lncRNAs in Breast Cancer Molecular Subtypes

ARID1A Downregulation Predicts High PD-L1 Expression and Worse Clinical Outcome in Patients With Gallbladder Cancer

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