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Published on: March 30, 2015
SNX4 Is Correlated With Immune Infiltration and Prognosis in Clear Cell Renal Cell Carcinoma
Yu Meng Chai1,2, Zhong Bao Zhou1,2, Run Ze Liu1
1Department of Urology, Beijing Tiantan Hospital, Capital Medical University, Beijing 100070, China.
Background:
Clear cell renal cell carcinoma (ccRCC) is known as the most common and malignant histologic subtype of renal carcinoma. Sorting nexin 4 (SNX4) plays a regulatory role in recycling from endosomes to the plasma membrane and promotes autophagosome assembly and transport, which may exert the cancerous growth and progression. This study aimed to assess the biological role of SNX4 in ccRCC and their clinical association via public biological data platforms combined with experimental verification.
Methods:
In our study, we analyzed the mRNA and protein expression of SNX4 in ccRCC under different clinicopathological characteristics through The Cancer Genome Atlas (TCGA), Human Protein Atlas (HPA) and Clinical Proteomic Tumor Analysis Consortium (CPTAC) databases. We used the Gene Expression Profiling Interactive Analysis (GEPIA) platform to conduct the survival analysis and figure out the immune cell infiltration level under different expression levels of SNX4 combined with Tumor Immune Estimation Resource (TIMER) database. Furthermore, we predicted competing endogenous RNA (ceRNA) regulatory network using TargetScan, miRDB, starBase and miRTarBase online databases. We totally collected six paired ccRCC tissues and adjacent tissues and applied quantitative real-time polymerase chain reaction (qRT-PCR) and western blot (WB) to detect the expression of SNX4 in the collected clinical specimens.
Results:
The mRNA and protein expression level of SNX4 was significantly lower in ccRCC than those in normal tissues. The results proposed that lower SNX4 was expressed in patients with higher histologic grade and in male patients. Kaplan-Meier analysis demonstrated that lower mRNA expression level of SNX4 was correlated with poorer prognosis. SNX4 had positive correlation with immune cell infiltrating levels and programmed cell death-ligand 1 (PD-L1) expression. Furthermore, we constructed the SNX4/miR-221-3p/miR-222-3p/DHRS4-AS1 axis, which may be the underlying ceRNA interaction network. Finally, we verified the reduced expression of SNX4 in ccRCC by qRT-PCR and WB.
Conclusion:
The expression of SNX4 in ccRCC was lower than adjacent tissues and its downregulated expression was associated with poor prognosis of ccRCC patients. SNX4 may exert critical roles in the tumorigenesis, development and migration of ccRCC via various mechanisms.
Insights
Sorting nexin 4 (SNX4) is downregulated in clear cell renal cell carcinoma (ccRCC), correlating with poorer prognosis and increased immune cell infiltration. This suggests SNX4 plays a role in ccRCC development and progression.
Area of Science:
- Oncology
- Molecular Biology
- Genomics
Background:
- Clear cell renal cell carcinoma (ccRCC) is the most common and aggressive kidney cancer subtype.
- Sorting nexin 4 (SNX4) is implicated in endosomal recycling and autophagy, processes potentially linked to cancer progression.
Purpose of the Study:
- To investigate the biological role and clinical significance of SNX4 in ccRCC.
- To analyze SNX4 expression patterns and their association with clinicopathological features and patient prognosis.
Main Methods:
- Utilized public databases (TCGA, HPA, CPTAC, GEPIA, TIMER) for expression and survival analysis.
- Predicted the competing endogenous RNA (ceRNA) network involving SNX4.
- Validated SNX4 expression in ccRCC tissues using qRT-PCR and Western Blot.
Main Results:
- SNX4 mRNA and protein levels were significantly reduced in ccRCC compared to normal tissues.
- Lower SNX4 expression was associated with higher histologic grade, male sex, and poorer patient prognosis.
- SNX4 positively correlated with immune cell infiltration and PD-L1 expression.
- A potential ceRNA network (SNX4/miR-221-3p/miR-222-3p/DHRS4-AS1) was identified.
Conclusions:
- Downregulated SNX4 expression is a hallmark of ccRCC and predicts unfavorable outcomes.
- SNX4 may be a critical regulator in ccRCC tumorigenesis, development, and migration.
- The identified ceRNA network offers potential therapeutic targets for ccRCC.
