The kidney renal papillary cell carcinoma (KIRP) is a relatively rare type of kidney cancer. There has been no investigation to find a robust signature to predict the survival outcome of KIRP patients in the aspect of tumor immunology. In this study, 285 KIRP samples from The Cancer Genome Atlas (TCGA) were randomly divided into training and testing set. A total of 1534 immune‐related genes from The Immunology Database and Analysis Portal (ImmPort) were used as candidates to construct the signature. Using univariate Cox analysis, we evaluated the relationship between overall survival and immune‐related genes expression and found 272 immune‐related genes with predicting prognostic ability. In order to construct an efficient predictive model, the Cox proportional hazards model with an elastic‐net penalty was used and identified 23 groups after 1000 iterations. As a result, 15‐genes model showing more stable than other gene groups was chosen to construct our immune‐related risk signature. In line with our expectations, the signature can independently predict the survival outcome of KIRP patients. Patients with high‐immune risk were found correlated with advanced stage. We also found that the high‐immune risk patients with higher PBRM1 and SETD2 mutations, increasing chromosomal instability, together with the gene set enrichment analysis (GSEA) results showing intensive connection of our signature with immune pathways. In conclusion, our study constructs a robust 15‐gene signature for predicting KIRP patients’ survival outcome on the basis of tumor immune environment and may provide possible relationship between prognosis and immune‐related biological function.
PIK3CA is a key component of phosphatidylinositol 3-kinase (PI3K) pathway that its involvement in tumorigenesis has been revealed by previous research. However, its functions and potential mechanisms in bladder cancer are still largely undiscovered. Tissue microarray (TMA) with 66 bladder cancer patients was surveyed via immunohistochemistry to evaluate the level of PIK3CA and CUX1 and we found upregulation of PIK3CA in bladder cancer tissue and patients with higher level of PIK3CA presented with poorer prognosis. Overly expressed PIK3CA promoted growth, migration, invasion, and metastasis of bladder cancer cells and knockdown of PIK3CA had the opposite effect. Gain-of-function and loss-of-function studies showed that PIK3CA expression was facilitated by CUX1, leading to activation of epithelial-mesenchymal transition (EMT), accompanied by upregulated expression of Snail, β-catenin, Vimentin and downregulated expression of E-cadherin in the bladder cancer cell lines. Besides, over-expressed CUX1 could restore the expression of downregulated Snail, β-catenin, Vimentin and E-cadherin which was induced by PIK3CA knockdown. These results revealed that PIK3CA overexpression in bladder cancer was regulated by the transcription factor CUX1, and PIK3CA exerted its biological effects by activating EMT.
Purpose: To evaluate the safety and feasibility of lingual mucosal graft ureteroplasty (LMGU) combined with ureteral reimplantation (UR) for repairing managing multifocal ureteral strictures (MUS). Methods: Between December 2020 and December 2022, 14 patients underwent LMGU combined with UR. Their perioperative data were collected retrospectively and analyzed. For the proximal diseased ureter, the narrow segment was incised longitudinally to open the ventral wall of ureter, and a lingual mucosal graft (LMG) was placed as an onlay graft. Meanwhile, UR was applied to treat distal ureteral strictures. Results: Of 14 patients, three (21.4%) had previously undergone a failed ureteral reconstruction. The mean (SD) proximal stricture length was 4.0 cm (1.56), distal ureteral stricture length was 4.3 cm (0.94). The mean (SD) operative time was 236 min (57), the estimated blood loss was 78 ml (41.5), and the length of postoperative stay was 6 days. One (7%) patient underwent double LMGU to treat proximal 2 segments of ureteral stricture. No open conversions and intraoperative complications occurred. With a mean follow-up of 15 months (range 6–29), the recurrence-free rate was 14/14 (100%). Conclusions: LMGU combined with UR is a feasible and effective technique for managing MUS and can be an alternative to IUR or renal autotransplantation in some selected patients with MUS.