Abstract
BackgroundKidney cancer is one of the most common cancers in the world. It is necessary to clarify its underlying mechanism and find its prognostic biomarkers. Current studies showed that SHMT2 may be participated in several kinds of cancer.MethodsOur studies investigated the expression of SHMT2 in kidney cancer by Oncomine, Human Protein Atlas database and ULCAN database. Meanwhile, we found its co-expression gene by cBioPortal online tool and validated their relationship in A498 and ACHN cells by cell transfection, western blot and qRT-PCR. Besides these, we also explored their prognostic values via the Kaplan–Meier plotter database in different types of kidney cancer patients.ResultsSHMT2 was found to be increased in 7 kidney cancer datasets, compared to normal renal tissues. For the cancer stages, ages and races, there existed significant difference in the expression of SHMT2 among different groups by mining of the UALCAN database. High SHMT2 expression is associated with poor overall survival in patients with kidney cancer. Among all co-expressed genes, NDUFA4L2 and SHMT2 had a high co-expression efficient. SHMT2 overexpression led to the increased expression of NDUFA4L2 at both mRNA and protein levels. Like SHMT2, overexpressed NDUFA4L2 also was associated with worse overall survival in patients with kidney cancer.ConclusionBased on above results, overexpressed SHMT2 and its co-expressed gene NDUFA4L2 were all correlated with the prognosis in kidney cancer. The present study might be benefit for better understanding the clinical significance of SHMT2 and provided a potential therapeutic target for kidney cancer in future.
Highlights
Kidney cancer is one of the most common cancers in the world
Serine Hydroxymethyltransferase 2 (SHMT2) was upregulated in 7 various kidney cancer datasets, compared to normol tissues (P‐value < 0.05 and Fold change > 2) including Renal Wilms Tumor [11], Clear Cell Renal Cell Carcinoma [11,12,13], Non-Hereditary Clear Cell Renal Cell Carcinoma [14] and Hereditary Clear Cell Renal Cell
We confirmed that mRNA expression levels of SHMT2 was significantly increased in renal clear cell carcinoma tissues than in normal renal tissues, which further verified the results from Gene Expression Profiling Interactive Analysis (GEPIA) database (Fig. 1h)
Summary
Kidney cancer is one of the most common cancers in the world. It is necessary to clarify its underlying mechanism and find its prognostic biomarkers. Despite great achievement in diagnosis and therapy, because of the Serine Hydroxymethyltransferase 2 (SHMT2), a protein coding gene, regulate glycine production in mitochondria, which is an essential intermediate for purine biosynthesis [4, 5] This gene is over-expressed in liver, lymph node and peripheral blood mononuclear cells. Wang et al Biol Res (2020) 53:46 marker in several cancers, including intrahepatic cholangiocarcinoma [6], large B cell lymphoma [7] and breast cancer [8]. Besides these studies, the mitochondrial onecarbon metabolic pathway involving in SHMT2 is associated with patient survival in pancreatic cancer and gastrointestinal cancer [9, 10]. Its expression profile and clinical significance of SHMT2 in human kidney cancer have not yet been investigated
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