Characterization of Long Non-coding RNA Signatures of Intracranial Aneurysm in Circulating Whole Blood

Tutino, Vincent M.; Poppenberg, Kerry E.; Damiano, Robert J.; Patel, Tatsat R.; Waqas, Muhammad; Dmytriw, Adam A.; Snyder, Kenneth V.; Siddiqui, Adnan H.; Jarvis, James N.

doi:10.1007/s40291-020-00494-3

Cited by 13 publications

(11 citation statements)

References 49 publications

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“…Transcriptome profiling is a powerful tool for revealing expression patterns that are associated with complex diseases [9,15,16], such as stroke. The ability to extract satisfactory RNA from blood clots for downstream applications has been proven difficult with traditional extraction methods.…”

Section: Discussionmentioning

confidence: 99%

Isolation of RNA from Acute Ischemic Stroke Clots Retrieved by Mechanical Thrombectomy

Tutino

Fricano

Frauens

et al. 2021

Genes

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Mechanical thrombectomy (MT) for large vessel acute ischemic stroke (AIS) has enabled biologic analyses of resected clots. While clot histology has been well-studied, little is known about gene expression within the tissue, which could shed light on stroke pathophysiology. In this methodological study, we develop a pipeline for obtaining useful RNA from AIS clots. A total of 73 clot samples retrieved by MT were collected and stored in RNALater and in 10% phosphate-buffered formalin. RNA was extracted from all samples using a modified Chemagen magnetic bead extraction protocol on the PerkinElmer Chemagic 360. RNA was interrogated by UV–Vis absorption and electrophoretic quality control analysis. All samples with sufficient volume underwent traditional qPCR analysis and samples with sufficient RNA quality were subjected to next-generation RNA sequencing on the Illumina NovaSeq platform. Whole blood RNA samples from three patients were used as controls, and H&E-stained histological sections of the clots were used to assess clot cellular makeup. Isolated mRNA was eluted into a volume of 140 µL and had a concentration ranging from 0.01 ng/µL to 46 ng/µL. Most mRNA samples were partially degraded, with RNA integrity numbers ranging from 0 to 9.5. The majority of samples (71/73) underwent qPCR analysis, which showed linear relationships between the expression of three housekeeping genes (GAPDH, GPI, and HPRT1) across all samples. Of these, 48 samples were used for RNA sequencing, which had moderate quality based on MultiQC evaluation (on average, ~35 M reads were sequenced). Analysis of clot histology showed that more acellular samples yielded RNA of lower quantity and quality. We obtained useful mRNA from AIS clot samples stored in RNALater. qPCR analysis could be performed in almost all cases, while sequencing data could only be performed in approximately two-thirds of the samples. Acellular clots tended to have lower RNA quantity and quality.

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Section: Discussionmentioning

confidence: 99%

Isolation of RNA from Acute Ischemic Stroke Clots Retrieved by Mechanical Thrombectomy

Tutino

Fricano

Frauens

et al. 2021

Genes

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“…Deep sequencing data have laid the foundation for identifying genes associated with cancer prognosis [25]. Currently, numerous studies are focusing on cancer prognosis-associated coding and non-coding RNA signatures [26][27][28]. However, most of these signatures require expression level quanti cation29.…”

Section: Discussionmentioning

confidence: 99%

An Immune-associated lncRNA Signature Predicts the Survival of Patients With Head and Neck Squamous Cell Carcinoma

Wang

Bian

Liu

et al. 2021

Preprint

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BackgroundThe malignant progression and treatment resistance of head and neck squamous cell carcinoma are closely related to the tumor immune microenvironment. Long non-coding RNA (lncRNA) plays a regulatory role in this process and may be exploited as new signatures for head and neck squamous cell carcinoma(HNSCC) diagnosis, prognosis, and treatment.MethodsHNSCC transcriptome data was abstracted from the Cancer Genome Atlas (TCGA) data resource, and uncovered immune-linked lncRNA through co-expression analysis. Besides, univariate along with Lasso penalty regression were employed to determine immune-linked lncRNA pairs with different expressions. We then compared area under the curve, calculated the Akaike information criterion (AIC) value of the receiver operating characteristic curve for 5 years, determined cutoff points, and established an optimal predictive model for identifying high- and low-risk HNSCC patients. Then, we evaluated these patients with high- and low-risk HNSCC in terms of survival, clinic-pathological characteristics, tumor-infiltrating immune cells, chemotherapeutic efficacy, and immunosuppressed biomarkers.ResultsThis study included 545 samples. By co-expression analysis of known immune-linked genes and lncRNAs, a total of 809 immune-related lncRNAs were collected. 77 differentially expressed immune-related lncRNAs were identified (logFC>2,FDR<0.01). The identified differentially-expressed immune-linked lncRNAs were used to develop differential immune-linked lncRNA pairs. Univariate and modified Lasso regression analysis identified 40 differentially expressed immune linked lncRNAs pairs, 17 of which were incorporated in the Cox proportional hazard model by a stepwise approach. The signature could well predict the survival of patients, and the area under the receiver operating characteristic (ROC) of 17 lncRNA pairs predicted 1, 3, and 5-year survival rates (AUC) were all greater than 0.74. Kaplan-Meier analysis found that patients at low risk had longer survival than those in the high-risk group (p<.001). In addition, T stage, survival status, N stage, and clinical stage, were remarkably linked to the risk. The high- and low risk groups were correlated with tumor invading immune cells like macrophages, CD8+ T-cells, monocytes, along with CD4+ T-cells. ICI-related biomarker correlation analysis showed high risk scores were positively linked to high CDK8 expression (p<0.001) and negatively correlated with BTLA , LAG3 and PDCD1 (p<0.001). High-risk scores were correlated with lower IC50 for chemotherapeutics like Docetaxel (p<0.01), indicating that this model can predict chemotherapeutic efficacy.ConclusionsOur results offer promising prospects for identifying innovative molecular targets of immunotherapy and to improve therapeutic approaches for head and neck squamous cell carcinoma patients.

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Section: Discussionmentioning

confidence: 99%

An Immune-associated lncRNA Signature Predicts the Survival of Patients With Head and Neck Squamous Cell Carcinoma

Wang

Bian

Liu

et al. 2021

Preprint

View full text Add to dashboard Cite

Recent researches have established that lncRNAs (long non-coding RNAs) could be exploited as new signatures for head and neck squamous cell carcinoma (HNSCC) diagnosis, prognosis, and treatment. Herein, HNSCC transcriptome data was abstracted from the Cancer Genome Atlas (TCGA) data resource, and uncovered immune linked lncRNAs through co-expression analysis. Besides, univariate along with Lasso penalty regression were employed to determine immune-linked lncRNA pairs with different expressions. We then compared area under the curve, calculated the Akaike information criterion (AIC) value of the receiver operating characteristic curve for 5 years, determined cutoff points, and established an optimal predictive model for identifying high- and low-risk HNSCC patients. Overall, we identified 40 differentially expressed immune-linked lncRNA pairs, 17 of which were incorporated in the Cox regression model. Using this model, we can more effectively stratify patients based on poor survival results, positive clinicopathological features, specific tumor immune invasion status, low chemotherapy responsivity, and high expression of immunosuppressive biomarkers. Our data illustrated that the immune-linked lncRNA pairs signature have clinical prediction value for HNSCC.

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Characterization of Long Non-coding RNA Signatures of Intracranial Aneurysm in Circulating Whole Blood

Cited by 13 publications

References 49 publications

Isolation of RNA from Acute Ischemic Stroke Clots Retrieved by Mechanical Thrombectomy

Isolation of RNA from Acute Ischemic Stroke Clots Retrieved by Mechanical Thrombectomy

An Immune-associated lncRNA Signature Predicts the Survival of Patients With Head and Neck Squamous Cell Carcinoma

An Immune-associated lncRNA Signature Predicts the Survival of Patients With Head and Neck Squamous Cell Carcinoma

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