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. 2022 Oct 15;8(10):e11079.
doi: 10.1016/j.heliyon.2022.e11079. eCollection 2022 Oct.

Two novel lncRNAs AF111167.2 and AL162377.1 targeting miR-21-5p mediated down expression of SYDE2 correlates with poor prognosis and tumor immune infiltration of ccRCC

Yuanshan Cui  1 , Jitao Wu  1 , Zhongbao Zhou  2 , Jian Ma  1 , Liying Dong  1
Affiliations

Two novel lncRNAs AF111167.2 and AL162377.1 targeting miR-21-5p mediated down expression of SYDE2 correlates with poor prognosis and tumor immune infiltration of ccRCC

Yuanshan Cui et al. Heliyon. .

Abstract

Advanced clear cell Renal Cell Carcinoma (ccRCC) is notoriously known for its poor prognosis. Synapse defective protein 1 homolog 2 encoded by the SYDE2 gene is a Rho GTPase-activating protein whose functional tumorigenic significance is still unclear. Recent pan-cancer analysis using the Cancer Genome Atlas (TCGA) and the Genotype-Tissue Expression (GTEx) data showed the potential tumor-suppressing effects of SYDE2 in ccRCC. Subsequently, the TCGA, GTEx data, and human protein atlas were employed to assess the correlation between the SYDE2 expression, clinical data, and overall survival (OS) in ccRCC patients. Furthermore, microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) contributing to SYDE2 down expression were identified by expression, relationship, and survival analysis. Eventually, two novel lncRNAs, AL162377.1 and AF111167.2, targeting the miR-21-5p axis, were identified in the SYDE2 upstream non-coding RNAs (ncRNAs)-related pathway in ccRCC. The expression level of SYDE2 highly depends on the tumor immune cell infiltration and immune checkpoint expression. In summary, these data demonstrated that lncRNAs/miRNAs-mediated down-regulation of SYDE2 is related to the tumor immune infiltration. Hence, giving an insight into the prognosis of ccRCC.

Keywords: Clear cell renal cell carcinoma; Immune infiltrates; Prognosis; SYDE2; ncRNAs.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Expression pattern of SYDE2 in Pan-cancer perspective. The mRNA expression of GSDMB was down regulated in 14 of 33 cancer types compared with normal tissues (ns:nonsense, p ≥ 0.05; ∗: p < 0.05; ∗∗: p < 0.01; ∗∗∗: p < 0.001).
Figure 2
Figure 2
The mRNA and protein expression of SYDE2 in ccRCC. (A) mRNA expression levels of SYDE2 in 539 ccRCC samples and 72 normal samples. (B) mRNA expression levels of SYDE2 in 72 ccRCC and matched-adjacent normal samples. (C) Tumor tissues: the protein levels of SYDE2 based on Human Protein Atlas. (D) Normal tissues: the protein levels of SYDE2 based on Human Protein Atlas (∗∗∗P < 0.001). ccRCC:Clear Cell Renal Cell Carcinoma.
Figure 3
Figure 3
Relationships between SYDE2 mRNA levels and clinical pathological characteristics. Lower expression levels of SYDE2 were observed in patients with high T stage (A), N stage (B), M stage (C), pathologic stage (D) and histologic grade (E). Higher levels of SYDE2 expression were identified in female patients (F) (∗P < 0.05, ∗∗P < 0.01,∗∗∗P < 0.001).
Figure 4
Figure 4
ROC and Kaplan-Meier curves for SYDE2. (A) ROC curve showed that GSDMB had an AUC value of 0.800 to discriminate ccRCC tissues from healthy controls. (B/C/D) Kaplan-Meier survival curves indicated that ccRCC patients with high SYDE2 mRNA expression had a longer OS, DSS and PFI than those with low-level of GSDMB. OS: overall survival; DSS: disease specific disease; PFI: progress free interval.
Figure 5
Figure 5
(A) The miRNA-SYDE2 regulatory network was established using cytoscape software. (B) miR-21-5p was one of the most significantly negatively correlated with SYDE2. (C to M) miR-21-5p was markedly upregulated in ccRCC and its upregulation was negatively linked to patients' prognosis. ccRCC:Clear Cell Renal Cell Carcinoma.
Figure 6
Figure 6
(A) The lncRNA-miR-21-5p regulatory network was constructed by cytoscape software. (B to J) novel lncRNAs AL162377.1, and AF111167.2 was markedly downregulated in ccRCC and its downregulation was negatively linked to patients' prognosis. ccRCC:Clear Cell Renal Cell Carcinoma.
Figure 7
Figure 7
(A) Significant changes of immune cell infiltration level (including B cell, CD8+T cell, CD4+ T cell, macrophage, neutrophil, and dendritic cell) under “arm-level deletion” copy number of SYDE2 in ccRCC was detected. (B)The correlation between the expression level (TPM) of SYDE2 and immune cell enrichment based on the Spearman correlation coefficient.
Figure 8
Figure 8
Relationship between SYDE2 and PD1/PD-L1 in ccRCC. (A–B) SYDE2 expression was significantly negatively correlated with PD1 in ccRCC. ccRCC:Clear Cell Renal Cell Carcinoma.
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