Stromal cell populations in the tumor microenvironment (TME) play a critical role in the oncogenesis and metastasis of renal cell carcinoma. In this study, we found that there are α-smooth muscle actin positive (α-SMA (+)) cells in the stroma of clear cell renal cell carcinoma (ccRCC) tissues, and their numbers are significantly associated with poor survival in ccRCC patients. Interleukin 6 (IL-6) is a critical diver that induces α-SMA (+) cells in ccRCC tissues via promotion of epithelial to mesenchymal transition (EMT) and stimulates migration and invasion in ccRCC. Peritumoral CD4+ T cells are the main source of IL-6 in ccRCC tissues. In addition to biochemical factors, mechanical compression within tumors affects tumor cell behavior. Tumors grown in a confined space exhibit intratumoral compressive stress and, with sufficient pressure, stress-stimulated migration of cancer cells. Moreover, a combination of IL-6 secreted by CD4+ T cells and growth-induced solid stress further contributes to the regulation of cancer cell morphogenesis, EMT and acquisition of a stemness phenotype. The effects in the combination group were driven by the Akt/GSK-3β/β-catenin signaling pathway, and deregulation of β-catenin expression was predictive of poor outcome in ccRCC patients. Notably, the expression of a cancer stem cell marker, CD44, was correlated with T stage, high Fuhrman grade and metastasis in ccRCC. These data provide evidence for new stress-reducing and IL-6 targeting strategies in cancer therapy.

Recently, long noncoding RNAs have emerged as new gene regulators and prognostic markers in several cancers, including renal cell carcinoma (RCC). Here, we focused on the long noncoding RNA lung cancer associated transcript 1 (LUCAT1) based on clear cell RCC (ccRCC) the cancer genome atlas (TCGA) data. However, whether aberrant expression of LUCAT1 in ccRCC is correlated with malignancy, metastasis or prognosis has not been elucidated. In the current study, we found that the expression of LUCAT1 was upregulated in ccRCC tissues and cancer cell lines. Upregulated LUCAT1 was positively correlated with larger tumor size, advanced tumor-node-metastasis (TNM) stage, higher smoking frequency, nodal metastasis and shorter overall survival in patients with ccRCC. Inhibition of LUCAT1 by small interfering RNA reduced cell proliferation and invasion of ccRCC cells in vitro. In vivo assay showed that the tumor volume and weight were lower in the group of LUCAT1 inhibition than that in the control group. We then found that LUCAT1 directly bound and inhibited the expression of micoRNA-495-3p (miR-495-3p), which subsequently regulated the expression of special adenine-thymine (AT)-rich DNA-binding protein 1 (SATB1). Collectively, LUCAT1 was critical for proliferation and invasion of ccRCC cells by regulating miR-495-3p and SATB1. Our findings indicated that LUCAT1 and miR-495-3p may offer potential novel therapeutic targets of treatment of ccRCC.

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Background: It is anticipated that there will be a large rise in the number of tumor diagnoses and mortality in those aged 65 and older over the course of upcoming decades. Immune checkpoint inhibitors, often known as ICIs, boost immune system activity by selectively targeting ICI genes. On the other hand, old age may be connected with unfavorable results. Methods: The Cancer Genome Atlas (TCGA) provided gene expression data from ccRCC tissue and key clinical variables. ICI gene databases were applied and verified using the GEO database. Results: We identified 14 ICI genes as risk gene signatures among 528 ccRCC patients using univariate and multivariable cox hazard models, and the elderly group was linked with poor survival. Then, by utilizing a new nomogram method, the TNFSF15 gene and age predicting values were estimated at one, three, and five years (85%, 81%, and 81%), respectively, and our age-related risk score was significant even after multivariable analysis (HR = 1.518, p = 0.009, CI = 1.1102.076). TNFSF15 gene expression was lower in elderly ccRCC patients (p = 0.0001). A negative connection between age and the TNFSF15 gene expression was discovered by correlation analysis (p = 0.0001). The verification of the gene by utilizing GEO (GSE167093) with 604 patients was obtained as external validation that showed significant differences in the TNFSF15 gene between young and elderly patients (p = 0.007). Additionally, the protein–protein interactions of the TNFSF15 gene with other ICI genes and aging-related genes was determined. In addition, the TNFSF15 expression was significantly correlated with pathological stages (p = 0.018). Furthermore, it was discovered that the biological processes of senescence, cellular senescence, the immune system, and many immune cell infiltration and immune function types are all closely tied. Conclusions: Along with the risk score evaluation, the ICI gene TNFSF15 was identified as a tumor suppressor gene related to inequalities in age survival and is associated with pathological stages and different immunity statuses. The aging responses of ccRCC patients and related gene expression need further investigation in order to identify potential therapeutic targets.

Renal cell carcinoma (RCC) is one of the most prevalent malignant tumors of the urinary system, accounting for around 2% of all cancer diagnoses and deaths worldwide. Clear cell RCC (ccRCC) is the most prevalent and aggressive histology with an unfavorable prognosis and inadequate treatment. Patients’ progression-free survival is considerably improved by surgery; however, 30% of patients develop metastases following surgery. Identifying novel targets and molecular markers for RCC prognostic detection is crucial for more accurate clinical diagnosis and therapy. Glycosylation is a critical post-translational modification (PMT) for cancer cell growth, migration, and invasion, involving the transfer of glycosyl moieties to specific amino acid residues in proteins to form glycosidic bonds through the activity of glycosyltransferases. Most cancers, including RCC, undergo glycosylation changes such as branching, sialylation, and fucosylation. In this review, we discuss the latest findings on the significance of aberrant glycans in the initiation, development, and progression of RCC. The potential biomarkers of altered glycans for the diagnosis and their implications in RCC have been further highlighted.

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BackgroundThis retrospective clinical study is to evaluate the safety and efficiency of two different approaches in retroperitoneal laparoscopic adrenalectomy and provide experience and basis for the treatment of adrenal tumors through retroperitoneal approach.MethodsFrom July 2015 to February 2018, 112 patients with adrenal lesions underwent retroperitoneal laparoscopic adrenalectomy (RLA) using a 3-port method. Among them, 56 patients underwent RLA via the extra perinephric fat approach (EPFA), 56 patients underwent RLA via the intra perinephric fat approach (IPFA). Clinical data, including preoperative, operative and postoperative management were recorded.ResultsAll surgeries were successfully completed, and there was no single patient who died during these surgeries. There was no statistically significant difference between the two groups in blood loss, postoperative complications, vena cava injury, renal cortex injury, peripheral organ injury, and post operation hospital stay. Peritoneum injury occurred more frequently in the EPFA group when compared with the IPEA group (p = 0.042). The average surgery time of the IPEA group is significantly shorter when compared with that of the EPEA group (p < 0.001). Due to serious saponification of the perinephric fat and heavy adhesion to renal fascia, three cases in IPFA group were converted to the EPFA surgery.ConclusionRLA is a safe and effective procedure both via extra perinephric fat and intra perinephric fat approaches. IPEA is superior to EPEA in terms of peritoneal injury and duration. The choice may mainly depend on the experience of the surgeon, the characteristics of the adrenal tumor and the nature of the perinephric fat.

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