Long non-coding RNA HOTTIP promotes renal cell carcinoma progression through the regulation of the miR-506 pathway.

HOXA transcript at the distal tip (HOTTIP), a lncRNA, induces cell proliferation and cancer progression. However, the expression and function of HOTTIP in renal cell carcinoma (RCC) were rarely reported. The role of the HOTTIP in RCC was explored in this study. HOTTIP expresses higher in RCC tissues than in normal tissues and indicates poor prognosis based on the TCGA database. The over- and low-expression HOTTIP cell line was established in this research to assess the oncogenic function of HOTTIP in RCC progression. Mechanistic analyses revealed that HOTTIP functioned as a competing endogenous RNA (ceRNA) for miR-506. RIP experiment and luciferase assay were performed to explore the mechanisms of the sponge between HOTTIP and miR-506. HOTTIP down-regulation attenuated cell proliferation, migration, and invasion, which could be rescued by miR-506 down-regulation. On the whole, this study revealed that the HOTTIP/miR-506 axis has a dominant impact on RCC progression and potentially provides a novel strategy for RCC diagnosis and therapy.

A Novel 7-Methylguanosine (m7G)-Related Gene Signature for Overall Survival Prediction in Patient with Clear Cell Renal Cell Carcinoma.

Clear cell renal cell carcinoma (ccRCC) is the most common pathology type of renal cancer that has an abysmal prognosis. Although a crucial role for 7-methylguanosine modification in cancer cell development has been reported, its role in ccRCC remains uncertain. This study was conducted to determine the efficacy of predictive biomarkers based on m7G-related genes in ccRCC. Firstly, we extracted clinical data and gene expression profiles of ccRCC patients from publicly accessible databases. It identified that 22 of the m7G-related 34 genes were related to overall survival, and 5 of the 22 genes were significantly expressed differently in tumor tissues. Based on Lasso regression analysis, five optimal genes (CYFIP2, EIF4A1, NUDT1, NUDT10, and NUDT4) were chosen to build a new predictive risk model in the TCGA cohort. Validation was carried out with the E-MTAB-1980 cohort. Then, a prognostic nomogram was erected, including the m7G-related gene risk score, age, histological grade, and stage status. Further studies and analysis showed that immune cell infiltration might be associated with the m7G-related risk genes. In addition, the relationship between gene expression and drug response was evaluated by the Pearson correlation test. Therefore, the risk signature with five selected m7G-related genes may be a promising prognostic biomarker and contribute to standardized prognostic assessment for ccRCC.

Association between multiple sclerosis and prostate cancer risk: A systematic review and meta­analysis.

Prostate cancer (PCa) risk in patients with multiple sclerosis (MS) remains to be elucidated. The present study conducted a meta-analysis to assess the relationship between MS and PCa. PubMed, EMBASE, Web of Science, and Cochrane Library databases were searched to identify studies on the PCa risk in patients with MS up to September 2022. A random effects meta-analyses model was performed to estimate the relative risk (RR) and the 95% confidence intervals (CI). All eight studies involving 210,943 patients with MS were identified and included in the meta-analysis. The present study revealed that there was no significant association between MS and the risk of PCa (RR=0.78, 95% CI: 0.56-1.08, P<0.0001). Subgroup analyses verified this conclusion when stratified by regions. However, after adjusting for potential confounders, the findings suggested conflicting results. The current evidence shows that compared with the population control, patients with MS have no relationship with PCa risk and further large samples and long-term trials are needed to verify these results.

Exploration of the immune microenvironment of breast cancer in large population cohorts.

Tumor immune microenvironment is associated with tumor progression. However, previous studies have not fully explored the breast cancer (BC) immune microenvironment. All the data analyzed in this study were obtained from the open-access database, including The Cancer Genome Atlas, Gene Expression Omnibus (TCGA), and cBioPortal databases. R software v4.0 and SPSS 13.0 were used to perform all the statistical analysis. Firstly, the clinical and expression profile information of TCGA, GSE20685, GSE20711, GSE48390, GSE58812, and METABRIC cohorts was collected. Then, 53 immune terms were quantified using the single-sample Gene Set Enrichment Analysis (ssGSEA) algorithm. A prognosis model based on HER2_Immune_PCA, IL12_score, IL13_score, IL4_score, and IR7_score was established, which showed great prognosis prediction efficiency in both training group and validation group. A nomogram was then established for a better clinical application. Clinical correlation showed that elderly BC patients might have a higher riskscore. Pathway enrichment analysis showed that the pathway of oxidative phosphorylation, E2F targets, hedgehog signaling, adipogenesis, DNA repair, glycolysis, heme metabolism, and mTORC1 signaling was activated in the high-risk group. Moreover, Tumor Immune Dysfunction and Exclusion and Genomics of Drug Sensitivity in Cancer analysis showed that low-risk patients might be more sensitive to PD-1 therapy, cisplatin, gemcitabine, paclitaxel, and sunitinib. Finally, four genes, XCL1, XCL2, TNFRSF17, and IRF4, were identified for risk group classification. In summary, our signature is a useful tool for the prognosis and prediction of the drug sensitivity of BC.

Correlations Between the Characteristics of Alternative Splicing Events, Prognosis, and the Immune Microenvironment in Breast Cancer.

OBJECTIVE: Alternative splicing (AS) is the mechanism by which a few genes encode numerous proteins, and it redefines the concept of gene expression regulation. Recent studies showed that dysregulation of AS was an important cause of tumorigenesis and microenvironment formation. Therefore, we performed a systematic analysis to examine the role of AS in breast cancer (Breast Cancer, BrCa) progression. METHODS: The present study included 993 BrCa patients from The Cancer Genome Atlas (TCGA) database in the genome-wide analysis of AS events. We used differential and prognostic analyses and found differentially expressed alternative splicing (DEAS) events and independent prognostic factors related to patients' overall survival (OS) and disease-free survival (DFS). We divided the patients into two groups based on these AS events and analyzed their clinical features, molecular subtyping and immune characteristics. We also constructed a splicing factor (SF) regulation network for key AS events and verified the existence of AS events in tissue samples using real-time quantitative PCR. RESULTS: A total of 678 AS events were identified as differentially expressed, of which 13 and 10 AS events were independent prognostic factors of patients' OS and DFS, respectively. Unsupervised clustering analysis based on these prognostic factors indicated that the Cluster 1 group had a better prognosis and more immune cell infiltration. SFs were significantly related to the expression of AS events, and AA-RPS21 was significantly upregulated in tumors. CONCLUSION: Alternative splicing expands the mechanism of breast cancer progression from a new perspective. Notably, alternative splicing may affect the patient's prognosis by affecting the infiltration of immune cells. Our research provides important guidance for subsequent studies of AS in breast cancer.

Incidence, Risk Factors and Prognosis of T4a Gastric Cancer: A Population-Based Study.

Background: T4a gastric cancer (GC) is a subtype of advanced GC (AGC), which urgently needs a comprehensive grade method for better treatment strategy choosing. The purpose of this study was to develop two nomograms for predicting the prognosis of patients with T4a GC. Methods: A total of 1,129 patients diagnosed as T4a GC between 2010 and 2015 were extracted from the Surveillance, Epidemiology, and End Result (SEER) program database. Univariate and multivariate Cox analyses were performed to explore the independent predictors and to establish nomogram for overall survival (OS) of the patients, whereas competing risk analyses were performed to find the independent predictors and to establish nomogram for cancer-specific survival (CSS) of the patients. The area under the curve (AUC), calibration curve, decision curve analysis (DCA), and Kaplan-Meier analysis were performed to evaluate the nomograms. Results: Older age, larger tumor size, black race, signet ring cell carcinoma (SRCC), more lymph node involvement, the absence of surgery, the absence of radiotherapy, and the absence of chemotherapy were identified as independent prognostic factors for both OS and CSS. In the training cohort, the AUCs of the OS nomogram were 0.760, 0.743, and 0.723 for 1-, 3-, and 5-year OS, whereas the AUCs of the CSS nomogram were 0.724, 0.703, and 0.713 for 1-, 3-, and 5-year CSS, respectively. The calibration curve and DCA indicated that both nomograms can effectively predict OS and CSS, respectively. The abovementioned results were also confirmed in the validation cohort. Stratification of the patients into high- and low-risk groups highlighted the differences in prognosis between the two groups both in training and in validation cohorts. Conclusions: Age, tumor size, race, histologic type, N stage, surgery status, radiotherapy, and chemotherapy were confirmed as independent prognostic factors for both OS and CSS in patients with T4a GC. Two nomograms based on the abovementioned variables were constructed to provide more accurate individual survival predictions for them.

High interleukin-8 and/or extracellular signal-regulated kinase 2 expression predicts poor prognosis in patients with hepatocellular carcinoma.

Interleukin (IL)-8 and extracellular signal-regulated kinase (ERK) 2 play key roles in tumor progression, but the relationship between IL-8 and/or ERK2 expression in hepatocellular carcinoma (HCC) tissues and postoperative recurrence or survival is unclear. The expression levels of IL-8 and ERK2 in both HCC tissues and non-tumor liver tissues were analyzed using the Oncomine™ database and immunohistochemistry assay. Reverse transcription-quantitative PCR was then used to evaluate the expression levels of IL-8 and ERK2 in the tumor tissues of 67 patients with HCC undergoing radical hepatectomy. Pearson's correlation, Kaplan-Meier, Cox univariate and multivariate survival analyses were utilized to determine the correlation between IL-8 and ERK2 expression in HCC tissues, and their potential prognostic significance. As indicated by the data from the Oncomine™ database, and the patient samples, IL-8 and ERK2 were expressed at significantly higher levels in HCC tissues than in non-tumor liver tissues (P<0.05). The rates of high IL-8 and ERK2 expression in HCC tissues were 43.28 (29/67) and 34.33% (23/67), respectively, and the IL-8 and ERK2 expression levels were positively correlated (r=0.764; P<0.001). Both ERK2 expression and IL-8/ERK2 co-expression were significantly associated with tumor size and differentiation (P<0.05). Additionally, high expression levels of IL-8, ERK2 and IL-8/ERK2 co-expression were all significantly associated with poor overall survival (OS; P<0.05) and disease-free survival (DFS; P<0.05). Multivariate Cox regression analysis also showed that high expression levels of IL-8, ERK2, and IL-8 and ERK2 were independent prognostic factors for OS and DFS (P<0.05). The results of the present study indicate a significant increase in the risk of recurrence and mortality in HCC patients with high expression levels of IL-8 and/or ERK2, compared with patients with low expression. Therefore, IL-8 and ERK2 may be predictors of postoperative prognosis in patients with HCC.

Isolated retroperitoneal enteric duplication cyst associated with an accessory pancreatic lobe.

INTRODUCTION: Enteric duplication cysts are rare congenital anomalies. They are lined by gastrointestinal mucosa, connected to the digestive tract, and share smooth muscle layers and a common blood supply. In rare cases, duplication cysts are isolated from the digestive tract and have a unique blood supply. No patient with isolated duplication cysts that are located in the retroperitoneum and associated with an accessory pancreatic lobe at the onset have been reported to date. MATERIALS AND METHODS: A 10-year-old Asian boy complained of left upper abdominal pain for more than 3 months. Contrast-enhanced computed tomography showed that the main pancreatic duct in the tail of the pancreas was dilated. A soft tissue density shadow was observed around the tail of the pancreas. The lesion was connected to the main pancreatic duct and the blood was supplied from a branch of the splenic artery. Surgical exploration and pathologic specimens resulted in the diagnosis of an isolated retroperitoneal enteric duplication cyst associated with an accessory pancreatic lobe. The patient received treatments of rehydration, antibiotics, and protease inhibitors. Due to the poor conservative treatment effect in internal medicine, a surgical resection of abnormal tissue was performed. RESULTS: The boy did not have abdominal pain again in the first year after leaving the hospital. DISCUSSION: For repeated abdominal pain in young people, especially in children, an enteric duplication cyst needs to be ruled out. This case was difficult to diagnose and imaging examination was not able to determine whether it is located in the anterior peritoneum or the retroperitoneum. For such cases, surgical exploration is necessary, and surgical resection can achieve more satisfactory results.