This is a preprint, a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Research
The N6-methyladenosine-modified Pseudogene HSPA7 Correlates with the Tumor Microenvironment and Predicts the Response to Immune Checkpoint Therapy in Glioblastoma
Gang Li
Shandong University Qilu Hospital
Corresponding Author
License:
This work is licensed under a CC BY 4.0 License. Read Full License
Background: Glioblastoma (GBM), one of the most aggressive cancers in brain tumor type, have no effective and sufficient therapies. Identifying robust biomarkers of immune checkpoint blockade (ICB) therapy, a promising treatment option for GBM patients, are urgently warranted.
Methods: We comprehensively evaluated the m6A modification patterns of lncRNAs via m6A-sequencing (m6A-seq) data of GBM tissues. And systematically investigated the immune and stromal regulators in these m6A regulated lncRNAs. We used the ssGSEA (single-sample gene-set enrichment analysis) algorithm to investigate the difference on enrichment of TME cell infiltration and functional annotation of HSPA7 in individual GBM sample.
Results: We depicted a transcriptome-wide m6A methylation profiling of lncRNAs in GBM for the first time, revealing the highly distinct m6A modification patterns of lncRNAs, compared to the normal brain tissues. And we identified m6A modified pseudogene HSPA7 as a novel risk prognostic factor for GBM patients, playing crucial roles in immunophenotype, stromal and carcinogenic pathways activation, having a robust predictive capacity of ICB immunotherapeutic response.
Conclusions: This work revealed that the m6A modified lncRNA HSAP7 played a nonnegligible role in tumor microenvironment (TME) cell infiltration, stromal and carcinogenic activation, and could be a robust predictive biomarker of ICB immunotherapy for GBM patients.
Keywords
N6-methyladenosine, long noncoding RNA, Tumor microenvironment, Glioblastoma, Immune checkpoint blockade
Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
This is a list of supplementary files associated with this preprint. Click to download.
- Supplementaryresultsandmethods.docx
Additional file 1—Supplementary results and methods.docx Fig. S1 Differentially expressed lncRNAs among immune， stromal and m6A regulated genes. Fig. S2 AC011899.9 was not significantly overexpressed in GBM tissues, compared with GETx normal brain tissues. Fig. S3 TME landscapes of GBM in TCGA database. Fig. S4 HSPA7 correlates with the immune suppression genes. Fig. S5-S6 The function of HSPA7 was verified in CGGA cohort1. Fig. S7 WTAP potentially regulate recruitment of the m6A methyltransferase complex to HSAP7 directly. Fig. S8 WTAP correlated with immunophenotypes and stromal activation pathways in CGGA GBM datasets. Fig. S9 The enrichment of HSPA7 interacting proteins identified in NCBI database. Fig. S10 HSPA7 correlated with the macrophage associated genes positively. Fig. S11 HSPA7 negatively correlated with TMB and MMR genes. Fig. S12 HSPA7 correlated with the immunophenotypes and stomal activation in bladder cancers. Fig. S13-S19 Characterization of HSPA7 across 33 cancer types.
- TableS1S7.xlsx
Additional file 2—Table S1-S7.xlsx Table S1: Immune cell types, immune pathway functions related gene sets. Table S2: Functional annotation and enriched pathways analysis related gene sets. Table S3: Differentially expressed lncRNAs between 153 primary GBM and 5 normal brain tissues in TCGA GBM cohort. Table S4: Tumorpurity, ESTIMATE, stromal and immune scores of 153 primary GBM cases in TCGA GBM cohort. Table S5: Differentially expressed lncRNAs between high and low immune score in TCGA GBM cohort. Table S6: Differentially expressed lncRNAs between high and low stromal score in TCGA GBM cohort. Table S7: Univariate and multivariate analysis of immune cells in TCGA GBM cohort.
- TableS8.xlsx
Additional file 3—Table S8.xlsx Table S8: HSPA7 postively correlated genes and enriched terms.
- TableS9.xlsx
Additional file 4—Table S9.xlsx Table S9: HSPA7 interacting proteins and enriched terms identified in NCBI database.
- TableS10.xlsx
Additional file 5—Table S10.xlsx Table S8: HSPA7 interacting proteins and enriched terms identified in stabase database.
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
History
CURRENT STATUS: Posted
Version 1
Posted 22 Dec, 2020
No community comments so far
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
Subject Areas
Cancer Biology
Learn more about our company.
This is a preprint. It has not completed peer review.
Research
The N6-methyladenosine-modified Pseudogene HSPA7 Correlates with the Tumor Microenvironment and Predicts the Response to Immune Checkpoint Therapy in Glioblastoma
Gang Li
Shandong University Qilu Hospital
Corresponding Author
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
History
CURRENT STATUS: Posted
Version 1
Posted 22 Dec, 2020
No community comments so far
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
Subject Areas
Cancer Biology
License:
This work is licensed under a CC BY 4.0 License. Read Full License
Background: Glioblastoma (GBM), one of the most aggressive cancers in brain tumor type, have no effective and sufficient therapies. Identifying robust biomarkers of immune checkpoint blockade (ICB) therapy, a promising treatment option for GBM patients, are urgently warranted.
Methods: We comprehensively evaluated the m6A modification patterns of lncRNAs via m6A-sequencing (m6A-seq) data of GBM tissues. And systematically investigated the immune and stromal regulators in these m6A regulated lncRNAs. We used the ssGSEA (single-sample gene-set enrichment analysis) algorithm to investigate the difference on enrichment of TME cell infiltration and functional annotation of HSPA7 in individual GBM sample.
Results: We depicted a transcriptome-wide m6A methylation profiling of lncRNAs in GBM for the first time, revealing the highly distinct m6A modification patterns of lncRNAs, compared to the normal brain tissues. And we identified m6A modified pseudogene HSPA7 as a novel risk prognostic factor for GBM patients, playing crucial roles in immunophenotype, stromal and carcinogenic pathways activation, having a robust predictive capacity of ICB immunotherapeutic response.
Conclusions: This work revealed that the m6A modified lncRNA HSAP7 played a nonnegligible role in tumor microenvironment (TME) cell infiltration, stromal and carcinogenic activation, and could be a robust predictive biomarker of ICB immunotherapy for GBM patients.
Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6