Background Glycolysis is a central metabolic pathway for tumor cells. However, the potential roles of glycolysis-related genes in renal cell carcinoma (RCC) have not been investigated. Methods Seven glycolysis-related gene sets were selected from MSigDB and were analyzed through GSEA. Using TCGA database, the glycolysis-related gene signature was constructed. Prognostic analyses were based on the Kaplan–Meier method. The cBioPortal database was employed to perform the mutation analyses. The CIBERSORT algorithm and TIMER database were used to determine the immunological effect of glycolytic gene signature. The expressions in protein level of eight glycolytic risk genes were determined by HPA database. Finally, qPCR, MTT and Transwell invasion assays were conducted to validate the roles of core glycolytic risk genes (CD44, PLOD1 and PLOD2) in RCC. Results Four glycolysis-related gene sets were significantly enriched in RCC samples. The glycolytic risk signature was constructed (including CD44, PLOD2, KIF20A, IDUA, PLOD1, HMMR, DEPDC1 and ANKZF1) and identified as an independent RCC prognostic factor (HR = 1.204). Moreover, genetic alterations of glycolytic risk genes were uncommon in RCC (10.5%) and glycolytic risk signature can partially affect immune microenvironment of RCC. Six glycolytic risk genes (except for IDUA and HMMR) were over-expression in A498 and 786-O renal cancer cells through qPCR test. MTT and Transwell assays revealed that silencing of CD44, PLOD1 and PLOD2 suppressed the proliferation and invasion of renal cancer cells. Conclusions The glycolysis-related risk signature is closely associated with RCC prognosis, progression and immune microenvironment. CD44, PLOD1 and PLOD2 may serve as RCC oncogenes.
Carcinoma progression is associated with the loss of epithelial features and the acquisition of a mesenchymal phenotype, a process known as epithelial-mesenchymal transition (EMT). Resveratrol, a natural polyphenolic compound found in grapes, berries and peanuts, has a wide range of pharmacological properties, including anti-tumor metastasis properties. The underlying mechanism through which resveratrol inhibits metastasis of prostate cancer (PCa) is not yet fully understood; however, it is thought to be associated with the disruption of EMT. In the present study, lipopolysaccharide (LPS) was used to trigger EMT in PC-3 and LNCaP PCa cell lines, and the cell lines were subsequently treated with resveratrol. The results demonstrated that exposure of PC-3 and LNCaP cells to LPS resulted in morphological alterations characteristic of EMT, as well as an increase in the expression of the mesenchymal marker vimentin and a decrease in the expression of E-cadherin. In addition, LPS exposure resulted in an increase in cell motility, along with an upregulation of the transcription factor glioma-associated oncogene homolog 1 (Gli1). However, treatment with resveratrol inhibited LPS-induced morphological changes, decreased the expression of LPS-induced markers of EMT and inhibited the expression of Gli1, resulting in the inhibition of in vitro cell motility and invasiveness. These results provide a novel perspective for the anti-invasion mechanism of resveratrol, suggesting that the effect is in part due to its ability to inhibit the EMT process through the Hedgehog signaling pathway.
Objective: The aim of this study was to examine the level of autophagy in renal clear cell carcinoma, stratify by clinicopathologic grades and stages and compare it with healthy renal tissue in order to hypothesize on the role of autophagy in the proliferation of renal clear cell carcinoma. Methods: Renal clear cell carcinoma tissue and matched adjacent tissue were collected from 52 patients who had received surgical resection. Autophagosomes were visualized in both renal clear cell carcinomas and adjacent tissue by transmission electron microscopy. Expression of the markers of autophagy, Beclin1 and LC3, was detected by a reverse transcription -polymerase chain reaction. Beclin1 and LC3 protein levels were examined by immunohistochemistry and western blot, and the correlation between autophagy levels and clinicopathologic data was analyzed. Results: Autophagy was down-regulated in renal clear cell carcinomas compared with matched adjacent tissue as measured by the reverse transcriptase-polymerase chain reaction, immunohistochemistry and western blot analyses. Clinicopathologic analyses indicated that advanced or metastatic renal clear cell carcinomas were associated with a lower expression of autophagy compared with localized renal clear cell carcinomas. Similarly, the Fuhrman nuclear grade of renal clear cell carcinomas was negatively correlated with the level of autophagy. Stage, grade and the level of LC3 II were significant factors for prognosis and the low level of LC3 II was associated with poor prognosis of renal clear cell carcinomas. Conclusions:The results indicate that autophagy is suppressed in renal clear cell carcinomas. The lower levels of autophagy are correlated with the higher stages and grades of renal clear cell carcinomas. Furthermore, a low level of LC3 II indicates poor prognosis of renal clear cell carcinoma. This is suggestive of association between the low level of autophagy and progression of renal clear cell carcinoma.
Rationale:Schwannomas are usually benign tumors arising from well-differentiated schwann cells, which rarely occur in the retroperitoneal space. The lack of specific signs and radiologic imaging characteristics makes preoperative diagnosis rather difficult. Most retroperitoneal schwannomas are benign and the primary treatment choice for retroperitoneal schwannomas is surgical excision, however, the involvement of the urinary system is scarcely reported.Patient concerns:A 34-year-old woman presented with progressive left abdominal pain and rebound abdominal mass at the left lower quadrant for 1 month. Radiological imaging suggested capsulated solid mass with cystic and necrotic areas in the retroperitoneum accompanied by severe left kidney hydronephrosis and preoperative biopsy result was inconclusive.Diagnoses:We believe this is a rare case of retroperitoneal schwannoma complicated with severe hydronephrosis.Interventions:After preparation, the patient underwent laparoscopy exploration and converted to open surgical exploration. The patient accepted complete surgical excision of the retroperitoneal tumor and left kidney. Postoperative pathology diagnosis of the mass was proven to be benign retroperitoneal schwannoma.Outcomes:Postoperative course of the patient was uneventful and the left abdominal pain was greatly improved. After 12-month follow up, no evidence of recurrence or any other complication including renal failure was observed.Lessons:Preoperative imaging and preoperative ultrasound-guided biopsy are helpful to make accurate diagnosis. The final diagnosis is based on postoperative histological and immunohistochemical findings. The primary treatment option is complete surgical resection of the retroperitoneal schwannoma and the involved upper urinary system when severe hydronephrosis occured. Local recurrence and overall survival are closely correlated with negative resection margins and pathology types.
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