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. 2019 Mar 5;9(4):653-667.
doi: 10.1002/2211-5463.12601. eCollection 2019 Apr.

An autophagy-related long non-coding RNA signature for glioma

Fangkun Luan  1 , Wenjie Chen  2 , Miao Chen  1 , Jun Yan  1 , Hao Chen  1 , Haiyue Yu  1 , Tieqi Liu  1 , Ligen Mo  1
Affiliations

An autophagy-related long non-coding RNA signature for glioma

Fangkun Luan et al. FEBS Open Bio. .

Abstract

Glioma is one of the most common types of malignant primary central nervous system tumor, and prognosis for this disease is poor. As autophagic drugs have been reported to induce glioma cell death, we investigated the potential prognostic role of autophagy-associated long non-coding RNA (lncRNA) in glioma patients. In this study, we obtained 879 lncRNAs and 216 autophagy genes from the Chinese Glioma Genome Atlas microarray, and found that 402 lncRNAs are correlated with the autophagy genes. Subsequently, 10 autophagy-associated lncRNAs with prognostic value (PCBP1-AS1, TP53TG1, DHRS4-AS1, ZNF674-AS1, GABPB1-AS1, DDX11-AS1, SBF2-AS1, MIR4453HG, MAPKAPK5-AS1 and COX10-AS1) were identified in glioma patients using multivariate Cox regression analyses. A prognostic signature was then established based on these prognostic lncRNAs, dividing patients into low-risk and high-risk groups. The overall survival time was shorter in the high-risk group than that in the low-risk group [hazard ratio (HR) = 5.307, 95% CI: 4.195-8.305; P < 0.0001]. Gene set enrichment analysis revealed that the gene sets were significantly enriched in cancer-related pathways, including interleukin (IL) 6/Janus kinase/signal transducer and activator of transcription (STAT) 3 signaling, tumor necrosis factor α signaling via nuclear factor κB, IL2/STAT5 signaling, the p53 pathway and the KRAS signaling pathway. The Cancer Genome Atlas dataset was used to validate that high-risk patients have worse survival outcomes than low-risk patients (HR = 1.544, 95% CI: 1.110-2.231; P = 0.031). In summary, our signature of 10 autophagy-related lncRNAs has prognostic potential for glioma, and these autophagy-related lncRNAs may play a key role in glioma biology.

Keywords: CCGA; TCGA; autophagy; glioma; long non‐coding RNA; prognostic signature.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Network of prognostic lncRNAs with co‐expressed autophagy genes in glioma. In the centric position, grey blue nodes indicate lncRNAs and the sky blue indicates autophagy genes. The coexpression network is visualized by cytoscape 3.4 software.
Figure 2
Figure 2
Kaplan–Meier survival curves for the 10 prognostic lncRNAs for glioma in CCGA dataset. The 10 autophagy‐related lncRNAs were found to be independent prognostic factors for glioma patients, of which five lncRNAs were unfavorable factors (TP53TG1, ZNF674‐AS1, COX10‐AS1, DDX11‐AS1 and SBF2‐AS1) and five lncRNAs were confirmed to be favorable prognostic factors for glioma (PCBP1‐AS1, DHRS4‐AS1, GABPB1‐AS1, MAPKAPK5‐AS1 and MIR4453HG).
Figure 3
Figure 3
Autophagy‐related lncRNA risk score analysis of glioma patients in CCGA. (A) The low and high score group for the autophagy‐related lncRNA signature in glioma patients. (B) The survival status and duration of glioma cases. (C) Heatmap of the 10 key lncRNAs expression in glioma. The color from blue to red shows an increasing trend from low levels to high levels.
Figure 4
Figure 4
Kaplan–Meier survival curves for the autophagy‐related lncRNA risk score for glioma in CCGA dataset. The Kaplan–Meier survival curves showed that the OS period is longer in the low‐risk group than that in the high‐risk group in the CCGA datasets (median OS 1211 vs 346 days; log rank P < 0.05).
Figure 5
Figure 5
Autophagy‐related lncRNA risk score analysis of glioma patients in TCGA. (A) The low and high score group for the autophagy‐related lncRNA signature in glioma patients. (B) The survival status and duration of glioma cases. (C) Heatmap of the 10 key lncRNAs expressed in glioma. The color from blue to red shows an increasing trend from low levels to high levels.
Figure 6
Figure 6
Kaplan–Meier survival curves for the autophagy‐related lncRNA risk score for glioma in TCGA dataset. Consistent with the results derived from the CGGA dataset, the high‐risk patients had a shorter median OS than that of the low‐risk patients in TCGA datasets (median OS 385 vs 468 days; log rank P = 0.012).
Figure 7
Figure 7
Gene set enrichment analysis indicated significant enrichment of hallmark cancer‐related pathways in the high‐risk group based on CCGA dataset. JAK, Janus kinase; NFKB, nuclear factor‐κB; TNFA, tumour necrosis factor α.
Figure 8
Figure 8
Gene set enrichment analysis indicated significant enrichment of the progression‐ and metastasis‐related pathway in the high‐risk group based on CCGA dataset.
Figure 9
Figure 9
Gene set enrichment analysis indicated significant autophagy‐related enrichment based on CCGA dataset.
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