Fibroblast Growth Factor 11 Enables Tumor Cell Immune Escape by Promoting T Cell Exhaustion and Predicts Poor Prognosis in Patients with Lung Adenocarcinoma.

Fibroblast growth factor 11 (FGF11) accelerates tumor proliferation in a variety of cancer types. This study aimed to examine the link between FGF11 and the prognosis of lung adenocarcinoma. FGF11 was searched in the Tumor Cancer Genome Atlas (TCGA) and ImmProt databases. The link between FGF11 and lung cancer clinical data was investigated using TCGA and Kaplan-Meier (KM)-plotter databases, and we developed a prediction model. Putative mechanisms of action were investigated using Gene Ontology (GO) and KEGG enrichment analyses. The GeneMANIA and STRING databases were used to search for genes that interact with FGF11, and the Tumor Immune Estimation Resource (TIMER) database was used to discover connections between FGF11 and immune cells, as well as any correlations with immune-related genes. We found that FGF11 expression was higher in the lung adenocarcinoma tissue than in the paracancerous tissue, and patients with high FGF11 expression had a lower overall survival, progression-free survival, and disease specific survival rate than those with low FGF11 expression. The expression of FGF11 was inversely linked to six types of infiltrating immune cells in the TIMER database and was associated with EGFR, VEGFA, BRAF, and MET expressions. The FGF11 gene is negatively correlated with the expression of most immune cells, mainly with various functional T cells including Th1, Th1-like, Treg, and Resting Treg characterization genes. These results indicate that FGF11 has the potential to be a new lung adenocarcinoma biomarker. It increases tumor cell immune escape by boosting T cell exhaustion in the tumor microenvironment, contributing to the poor prognosis of the patients with lung adenocarcinoma. These results provide incentive to further research FGF11 as a possible biomarker and drug target for patients with lung adenocarcinoma.

CircSMARCC1 facilitates tumor progression by disrupting the crosstalk between prostate cancer cells and tumor-associated macrophages via miR-1322/CCL20/CCR6 signaling.

BACKGROUND: Circular RNAs (circRNAs) mediate the infiltration of tumor-associated macrophages (TAMs) to facilitate carcinogenesis and development of various types of cancers. However, the role of circRNAs in regulating macrophages in prostate cancer (PCa) remains uncertain. METHODS: Differentially expressed circRNAs in PCa were identified by RNA sequencing. The expression of circSMARCC1 was recognized and evaluated using fluorescence in situ hybridization and quantitative real-time PCR. The oncogenic role of circSMARCC1 in PCa tumor proliferation and metastasis was investigated through a series of in vitro and in vivo assays. Finally, Western blot, biotin-labeled RNA pulldown, luciferase assay, rescue experiments, and co-culture experiments with TAMs were conducted to reveal the mechanistic role of circSMARCC1. RESULTS: CircSMARCC1 was dramatically up-regulated in PCa cells, plasma and tissues. Overexpression of circSMARCC1 promotes tumor proliferation and metastasis both in vitro and in vivo, whereas knockdown of circSMARCC1 exerts the opposite effects. Mechanistically, circSMARCC1 regulates the expression of CC-chemokine ligand 20 (CCL20) via sponging miR-1322 and activate PI3K-Akt signaling pathway involved in the proliferation and epithelial mesenchymal transformation. More importantly, high expression of circSMARCC1 was positively associated with colonization of CD68+/CD163+/CD206+ TAMs in tumor microenvironment. In addition, overexpression of circSMARCC1 facilitates the expression of CD163 in macrophages through the CCL20-CCR6 axis, induces TAMs infiltration and M2 polarization, thereby leading to PCa progression. CONCLUSIONS: CircSMARCC1 up-regulates the chemokine CCL20 secretion by sponging miR-1322, which is involved in the crosstalk between tumor cells and TAMs by targeting CCL20/CCR6 signaling to promote progression of PCa.

VRK1 Predicts Poor Prognosis and Promotes Bladder Cancer Growth and Metastasis In Vitro and In Vivo.

Bladder cancer (BC) is one of the most common malignant tumors in the urinary system with growing morbidity and diagnostic rate in recent years. Therefore, identifying new molecular biomarkers that inhibit the progression of bladder cancer is needed for developing further therapeutics. This study found a new potential treatment target: vaccinia-related kinase 1 (VRK1) and explored the function and mechanism of VRK1 in the development of bladder cancer. First, TCGA database and tissue microarray analysis showed that VRK1 was significantly upregulated in bladder cancer. Kaplan-Meier survival analysis indicates that the OS and PFS of the VRK1 high expression group were significantly lower than the VRK1 low expression group (p = 0.002, p = 0.005). Cox multi-factor analysis results show that VRK1 expression is an independent risk factor affecting tumor progress. The maximum tumor diameter, staging, and adjuvant chemotherapy also have a certain impact on tumor progression (p < 0.05). In internal validation, the column C index is 0.841 (95% CI, 0.803-0.880). In addition, cell functional studies have shown that VRK1 can significantly inhibit the proliferation, migration, and invasiveness of bladder cancer cells. In vivo, nude mice transplanted tumors further prove that low VRK1 can significantly inhibit the proliferation capacity of bladder cancer cells. In summary, VRK1 expression is significantly related to the staging, grade, and poor prognosis of patients with bladder cancer. At the same time, in vivo and in vitro experiments have shown that downregulation of VRK1 can significantly inhibit the proliferation of bladder cancer cells. These findings provide a basis for using VRK1 as a potential therapeutic target for patients with bladder cancer.

Predictive value of the hemoglobin, albumin, lymphocyte, and platelet (HALP) score and lymphocyte-to-monocyte ratio (LMR) in patients with non-small cell lung cancer after radical lung cancer surgery.

BACKGROUND: Examining the analytical worth of the preoperative hemoglobin, albumin, lymphocyte, platelet (HALP) score and lymphocyte-to-monocyte ratio (LMR) within diseased persons having non-small cell lung cancer (NSCLC) after radical lung cancer surgery. METHODS: Clinical data concerning 238 diseased persons with NSCLC who underwent radical lung cancer resection within Nantong Cancer Hospital between January 2009 and October 2015 had been looking back studied. ROC curve had been employed in regulating optimal critical worth of HALP and LMR that had been 48.00 and 6.30 singly. A 5-year amplification observed survival concerning diseased persons, and clinicopathological stuff assessed using statistics procedure. Kaplan Meier method, log rank test had been exploited from the point of view to analyze for surviving, and Cox regression analysis had been exploited for univariate and multivariate analysis. Eventually, a nomogram had been produced to examine the confirmation internally. RESULTS: Kaplan Meier survival assessment revealed top HALP class's overall survival (OS) was significantly higher than below HALP class's (P<0.001), and high LMR group's OS was also greater than below LMR class's (P=0.001). Patients possessing average continuance period of 4 years. Further stratified study revealed high HALP class possessed notable OS as compared below HALP class (P=0.0002), and top LMR class possessed considerable OS as compared to below LMR class (P=0.003) in lung adenocarcinoma. In non-adenocarcinoma, there was no substantial difference in OS between two classes (P>0.05). Preoperative HALP and LMR remained independent risk constituents for tumor progression (P=0.005, P=0.028), lymph node metastasis and level of differentiation also had a certain effect on tumor progression (P<0.05), according to Cox multivariate analysis. Rise in HALP and LMR will help diseased persons having NSCLC live longer. The nomogram's c-index in inside validation was 0.672 (95% confidence interval: 0.626-0.718). CONCLUSIONS: Preoperative HALP versus LMR are independent predictive aspect within NSCLC diseased persons linked to clinicopathological features, and has a particular value in determining bodement.

Low Expression of Keratin17 is Related to Poor Prognosis in Bladder Cancer.

OBJECTIVE: To investigate the association between KRT17 and the prognosis in bladder cancer patients. METHODS: The clinical data of 101 patients with bladder cancer from May 2013 to May 2015 were retrospectively analyzed. At the same time, the expression of KRT17 and its correlation with clinicopathological factors were examined by immunohistochemistry. We search the prognostic value of KRT17 in bladder cancer from the cancer genome map (TCGA) online database. To explore the possible cellular mechanism, gene set enrichment analysis (GSEA) was used. The patients were divided into two groups: high expression of KRT17 and low expression of KRT17. The patients were followed up for 5 years to observe the survival. Kaplan-Meier method and Log rank test were used for univariate survival analysis, and Cox regression analysis was used for multivariate analysis. Finally, a nomogram was constructed on this basis for internal verification. RESULTS: Among the 101 patients, 46 (45.5%) were in the KRT17 low expression group and 55 (54.5%) in the high KRT17 expression group. After 5 years of follow-up, 79 patients survived with a survival rate of 78.2% and 22 patients died with a mortality rate of 21.8%. Kaplan-Meier survival analysis showed that OS and PFS of patients with high expression of KRT17 were significantly higher than those of patients with low expression of KRT17 (p<0.001, p=0.005). Cox multivariate analysis showed that KRT17 expression was an independent risk factor for tumor progression (p=0.019). And tumor size, vascular tumor thrombus, and T stage also affected tumor progression (p<0.05). In the internal validation, the c-index of nomogram was 0.898 (95% CI: 0.854-0.941). CONCLUSION: The decreased expression of KRT17 is associated with poor prognosis in patients with bladder cancer. KRT17 can be used as a novel predictive biomarker to provide a new therapeutic target for bladder cancer patients.

Relationship and prognostic significance between preoperative serum albumin to globulin ratio and CT features of non-small cell lung cancer.

PURPOSE: This study was conducted to assess the relationship and prognostic significance between preoperative serum albumin to globulin ratio (AGR) and high-resolution computed tomography (HRCT) features of non-small cell lung cancer (NSCLC). MATERIALS AND METHODS: Demographic parameters, laboratory values including AGR and other clinical variables were evaluated in 180 patients with NSCLC, and 72 of these patients had results of radiology parameters detected with HRCT [including emphysema, tumor disappearance rate (TDR), CT values and CT enhanced values of the tumor mass] were assessed for survival analyses. The 72 patients were divided into two groups: normal lung group and emphysema group. The discriminatory values for AGR between these two groups were assessed by Mann-Whitney U test The relationship between TDR and AGR in NSCLC patients was evaluated by Pearson correlation analysis. RESULTS: In multivariate analysis, TDR (p = 0.033), AGR (p = 0.038), emphysema (p = 0.009), and N stage (P = 0.026) were independent predictors of overall survival (OS). AGR was higher in NSCLC patients without emphysema than NSCLC patients with emphysema (z = -2.979, P = 0.003). TDR demonstrated that there was a positive relationship with AGR (r = 0.307, p = 0.009). A nomogram with AGR, TDR, emphysema, and N stage was established to predict 5-year survival. CONCLUSIONS: There is a relationship between CT features and AGR in NSCLC. The integrative nomogram combined with CT images, clinical and hematologic features improved survival prediction in NSCLC patients, which offers a non-invasive, comprehensive, and convenient evaluation for individualized management of NSCLC patients.