SIRT7 is a prognostic biomarker in kidney renal clear cell carcinoma that is correlated with immune cell infiltration

Background: SIRT7 has been shown to be expressed in many cancer types, including kidney renal clear cell carcinoma (KIRC), but its functional role in this oncogenic context remains to be firmly defined. This study was designed to explore correlations between SIRT7 and KIRC characteristics using the TCGA database. Methods: Relationships between SIRT7 expression and KIRC patient clinicopathological characteristics were assessed through Kruskal-Wallis tests, Wilcoxon signed-rank tests, and logistic regression analyses. Area under the ROC curve (AUC) values were used to assess the prognostic value of SIRT7 as a means of classifying KIRC patients. The functional role of SIRT7 in this cancer type was assessed through GO/KEGG enrichment analyses and immune cell infiltration analyses. Results: In KIRC patients, higher levels of SIRT7 expression were associated with Race, M stage, T stage (all P < 0.05). SIRT7 offered significant diagnostic value in ROC curve analyses (AUC = 0.912), and elevated SIRT7 levels were linked to worse patient overall survival (OS; P < 0.001). The expression of SIRT7 was independently related with KIRC patient OS (HR: 1.827; 95%CI: 1.346-2.481; P<0.001). In GO/KEGG analyses, SIRT7 was found to be associated with ubiquitin-mediated proteolysis and nucleotide excision repair. Higher SIRT7 expression was related to the enhanced infiltration of certain immune cells.Conclusions: Increased SIRT7 expression was associated with a worse KIRC patient prognosis, and immune infiltrates, suggesting it may offer value as a prognostic biomarker for this cancer type.

Clear Cell Carcinoma of the Pancreas Infiltrating Duodenum: A Case Report of a Multiface Aspect of an Intriguing Entity

Background: Although Clear-cell carcinoma has been found in various organs as a variant of ductal carcinoma of the pancreas, it still hasn’t been well recognized. According to the WHO classification, primary Clear-cell carcinoma of the pancreas is rare, and it is classified as a “miscellaneous” carcinoma. To date it has been poorly characterized and only few cases have been reported in the literature [1]. Case presentation: We report here an unusual case of Clear-cell carcinoma in a 59-year-old man involving the head of the pancreas and the second part of the duodenum initially misconceived as pyloric gland adenoma, a rare duodenal entity. Nevertheless, duodenal sub stenosis was suspected of malignancy, so further investigations were made. Subsequent abdominal computed tomography (CT) detected not only a duodenal vegetation but also an alteration of the duodenal-pancreatic interface with thickening of the duodenal wall and a common bile duct dilatation. The malignant clinical aspect and behavior of the lesion, associated to the impossibility of further investigations due to the duodenal sub stenosis, led to an exploratory laparotomy.The laparotomy revealed a retracting area straddling the duodenum and the pancreatic head. A duodenum pancreatectomy of the head of the pancreas with extended lymphadenectomy was performed and the histological evaluation showed a ductal Clear-cell adenocarcinoma of the pancreas infiltrating the duodenum. The postoperative course was characterized by a pancreatic fistula grade B. At 6 months from the surgery, the patient hasn’t had recurrence.Conclusion: Because it is a rare tumor with very few cases reported previously, the incidence and prognosis are not well known for this neoplasm. The report of our case would aid in the identification of this rare neoplasm. Further studies and more case reports are needed to clarify the diagnosis and prognostic significance of the clear cell differentiation of these tumors.

Hypoxia-related lncRNA Signature to Predict the Survival of Patients with Clear Cell Renal Cell Carcinoma

Background: Renal cell carcinoma is the most common aggressive tumor of the genitourinary system. The main pathological subtype is clear cell renal cell carcinoma (ccRCC), and its treatment options are very limited. Therefore, identifying specific markers of renal clear cell carcinoma is of great significance for diagnosis and prognosis.Methods: From the TCGA database, we obtained information on 611 patients with renal clear cell carcinoma to analyze the relationship between hypoxia-related lncRNAs and overall survival. According to the coexpression of hypoxia genes and lncRNAs, genes related to hypoxia were identified. Difference analysis and Cox regression analysis were applied to assess survival-related risk factors. According to the median risk score of hypoxia-related genes, patients were divided into high-risk and low-risk groups. According to these gene characteristics and clinical parameters, a nomogram map was built, and GSEA was used for gene function annotation. RT-qRCR, Western Blot and Flow Cytometry were used to determine the role of SNHG19 in RCC cells.Results: By analyzing the coexpression of hypoxia genes and lncRNAs, 310 hypoxia-related genes were obtained. Six sHRlncRs were significantly correlated with the clinical outcomes of patients with ccRCC. Four sHRlncRs (AC011445.2, PTOV1-AS2, AP004609.3, and SNHG19) with the highest prognostic values were included in the group to construct the HRRS model. The high-risk group had a shorter OS than the low-risk group. HR-lncRNAs were considered to be an independent prognostic factor and associated with OS. The high- and low-risk groups showed different pathways in GSEA. Experiments showed that SNHG19 plays essential roles in autophagy and apoptosis of RCC cells.Conclusion: Our research shows that we established and verified a hypoxia-related lncRNA model that accurately correlates with ccRCC patients. This study also provides novel insights into hypoxia-based mechanisms and provides new biomarkers for the poor prognosis of ccRCC patients.

Identification of TRPM2 as a Marker Associated With Prognosis and Immune Infiltration in Kidney Renal Clear Cell Carcinoma

TRPM2 (transient receptor potential melastatin-2), a Ca2+ permeable, non-selective cation channel, is highly expressed in cancers and regulates tumor cell migration, invasion, and proliferation. However, no study has yet demonstrated the association of TRPM2 with the prognosis of cancer patients or tumor immune infiltration, and the possibility and the clinical basis of TRPM2 as a prognostic marker in cancers are yet unknown. In the current study, we first explored the correlation between the mRNA level of TRPM2 and the prognosis of patients with different cancers across public databases. Subsequently, the Tumor Immune Estimation Resource (TIMER) platform and the TISIDB website were used to assess the correlation between TRPM2 and tumor immune cell infiltration level. We found that 1) the level of TRPM2 was significantly elevated in most tumor tissues relative to normal tissues; 2) TRPM2 upregulation was significantly associated with adverse clinical characteristics and poor survival of kidney renal clear cell carcinoma (KIRC) patients; 3) the level of TRPM2 was positively related to immune cell infiltration. Moreover, TRPM2 was closely correlated to the gene markers of diverse immune cells; 4) a high TRPM2 expression predicted worse prognosis in KIRC based on different enriched immune cell cohorts; and 5) TRPM2 was mainly implemented in the T-cell activation process indicated by Gene Ontology (GO) function and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. In conclusion, TRPM2 can serve as a marker to predict the prognosis and immune infiltration in KIRC through the regulation of T-cell activation. The current data may provide additional information for further studies surrounding the function of TRPM2 in KIRC.

Treatment of kidney clear cell carcinoma, lung adenocarcinoma and glioblastoma cell lines with hydrogels made of DNA nanostars

Overcoming the systemic administration of chemotherapy to reduce drug toxicity and the application of personalised medicine are two of the major challenges in the treatment of cancer. To this aim,...