Search

Laryngeal squamous cell carcinoma (LSCC) is the most common malignant tumor, which occurs in the head and neck. Current treatments for LSCC are all largely weakened by increasing drug resistance. Our study aimed to investigate the effects of long noncoding RNA (lncRNA) H19 on drug resistance in LSCC. In our study, we found that the level of H19 was sharply upregulated in LSCC tissues and drug‐resistant cells compared with the control. Besides, the expression of high‐mobility group B1 (HMGB1) was elevated, and microRNA107 (miR‐107) was suppressed in drug‐resistant cells compared with the control. Further study revealed that the interference of H19 by short hairpin RNA (shRNA) effectively suppressed high autophagy level and obvious drug resistance in drug‐resistant cells. Besides that, miR‐107 was predicted as a target of H19 and inhibiting effects of H19 shRNA on autophagy and drug resistance were both reversed by miR‐107 inhibitor. Moreover, HMGB1 was predicted as a target of miR‐107 in LSCC cells and knockdown of HMGB1 was able to suppress autophagy and drug resistance in LSCC cells. In addition, our investigation demonstrated that H19 shRNA exerted an inhibiting effect on autophagy and drug resistance by downregulating HMGB1 by targeting miR‐107. Finally, the in vivo experiment revealed that LV‐H19 shRNA strongly suppressed drug resistance compared with the usage of cisplatin individually. Taken together, our research indicated an H19–miR‐107–HMGB1 axis in regulating the autophagy‐induced drug resistance in LSCC in vitro and in vivo, providing novel targets for molecular‐targeted therapy and broadening the research for LSCC. [ABSTRACT FROM AUTHOR]

MiR‐130b and SAM and SH3 domain containing 1 (SASH1) play an important role in many types of human cancers. The aim of our research was to study their interactions in the process of the proliferation and aggressiveness of oesophageal squamous cell carcinoma (ESCC) cells. Microarray analysis was done to screen the differentially expressed genes in the ESCC tissues. miR‐130b and SASH1 mRNA levels in the ESCC tissues and cells were detected by qRT‐PCR. Dual luciferase reporter system was used to verify the target relationship between miR‐130b and SASH1. The effects of miR‐130b on SASH1 expression were explored by western blot in KYSE30 and TE1 cell lines. CCK‐8 assay, flow cytometry, Transwell, and wound healing assays were conducted to explore the effects of miR‐130b and SASH1 in vitro. In addition, in vivo experiments were conducted to study the roles of miR‐130b and SASH1. miR‐130b was highly expressed, while SASH1 was the opposite in both the ESCC tissues and cells. The expression of SASH1 was inhibited by the direct binding of miR‐130b. The inhibition of miR‐130b reduced the proliferation and aggressiveness of ESCC cells, while it also induced apoptosis and cell cycle arrest in the ESCC cells by suppressing SASH1. The in vivo assay suggested that the overexpression of miR‐130b promoted the growth of ESCC tumours. MiR‐130b was up‐regulated in the ESCC tumour tissues and cells, acting as a tumour promoter. A stimulating effect was demonstrated on ESCC cell growth and aggressiveness by suppressing SASH1, which is an anti‐oncogene. [ABSTRACT FROM AUTHOR]

Objectives: Hepatocellular carcinoma (HCC) patients at the same stage exhibit different prognosis, and the underlying molecular mechanism remains unclear. This study aims to identify the key genes impacting the prognosis of HCC patients., Methods: Differentially expressed gene analyses were performed between HCC samples and normal ones, and between patients with long overall survival (OS) and those with short OS, in TCGA-LIHC and GSE14520 datasets. The Kaplan-Meier method with log-rank test was used to evaluate the role of secreted phosphoprotein 2 (SPP2) in the prognosis of HCC patients. Gene set enrichment analysis (GSEA) was used to understand the difference of enriched signaling pathways between SPP2-stratified HCC subgroups. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed to predict the potential functional pathways in which SPP2 might participate., Results: SPP2 was significantly down-regulated in tumors when compared with normal tissues, or in tumor samples with short OS when compared with those with long OS [fold change (FC)>2 and false discovery rate (FDR)<0.05]. Low expression of SPP2 was associated with worse clinicopathological features like vascular invasion ( P =1.6e-05), poor cancer status (with tumor, P =0.021), advanced T stage (T3 or T4, P =4.5e-04), advanced TNM stage (stage III or IV, P =3.1e-04), and with unfavorable prognosis (shorter OS, P =0.002). Gene enrichment analyses revealed that SPP2 might involve in the metabolic homeostasis of HCC and in the development of liver fibrosis and cirrhosis., Conclusions: SPP2 might inhibit the development of liver fibrosis and cirrhosis and the tumorigenesis of HCC, and analogs of SPP2 might be potential drugs in the prevention of these diseases.

Objectives: Hepatocellular carcinoma (HCC) prognosis involves multiple clinical factors. Although nomogram models targeting various clinical factors have been reported in early and locally advanced HCC, there are currently few studies on complete and effective prognostic nomogram models for stage IV HCC patients. This study aims to creat nomograms for cancer-specific survival (CSS) in patients at stage IV of HCC and developing a web predictive nomogram model to predict patient prognosis and guide individualized treatment., Methods: Clinicopathological information on stage IV of HCC between January, 2010 and December, 2015 was collected from the Surveillance, Epidemiology, and End Results (SEER) database. The patients at stage IV of HCC were categorized into IVA (without distant metastases) and IVB (with distant metastases) subgroups based on the presence of distant metastasis, and then the patients from both IVA and IVB subgroups were randomly divided into the training and validation cohorts in a 7꞉3 ratio. Univariate and multivariate Cox regression analyses were used to analyze the independent risk factors that significantly affected CSS in the training cohort, and constructed nomogram models separately for stage IVA and stage IVB patients based on relevant independent risk factors. Two nomogram's accuracy and discrimination were evaluated by receiver operator characteristic (ROC) curves and calibration curves. Furthermore, web-based nomogram models were developed specifically for stage IVA and stage IVB HCC patients by R software. A decision analysis curve (DCA) was used to evaluate the clinical utility of the web-based nomogram models., Results: A total of 3 060 patients were included in this study, of which 883 were in stage IVA, and 2 177 were in stage IVB. Based on multivariate analysis results, tumor size, alpha-fetoprotein (AFP), T stage, histological grade, surgery, radiotherapy, and chemotherapy were independent prognostic factors for patients with stage IVA of HCC; and tumor size, AFP, T stage, N stage, histological grade, lung metastasis, surgery, radiotherapy, and chemotherapy were independent prognostic factors for patients with stage IVB HCC. In stage IVA patients, the 3-, 6-, 9-, 12-, 15-, and 18-month areas under the ROC curves for the training cohort were 0.823, 0.800, 0.772, 0.784, 0.784, and 0.786, respectively; and the 3-, 6-, 9-, 12-, 15-, and 18-month areas under the ROC curves for the validation cohort were 0.793, 0.764, 0.739, 0.773, 0.798, and 0.799, respectively. In stage IVB patients, the 3-, 6-, 9-, and 12-month areas under the ROC curves for the training cohort were 0.756, 0.750, 0.755, and 0.743, respectively; and the 3-, 6-, 9-, and 12-month areas under the ROC curves for the validation cohort were 0.744, 0.747, 0.775, and 0.779, respectively; showing that the nomograms had an excellent predictive ability. The calibration curves showed a good consistency between the predictions and actual observations., Conclusions: Predictive nomogram models for CSS in stage IVA and IVB HCC patients are developed and validated based on the SEER database, which might be used for clinicians to predict the prognosis, implement individualized treatment, and follow up those patients.

Objectives: Tumor markers have been widely used clinically. Detection of serum CA125 is one of the commonly used clinical methods for early screening and early diagnosis of epithelial ovarian cancer, but it is difficult to diagnose epithelial ovarian cancer with a single specific tumor marker. In this study, the combinatorial tumor marker detection method was used to compare the value of each tumor marker alone and different combinations in the diagnosis of epithelial ovarian cancer., Methods: The clinical data of patients with epithelial ovarian cancer ( n =65) and ovarian benign disease ( n =29) were collected. Multiple tumor marker protein chip was used to detect cancer antigen 125 (CA125), carbohydrate antigen 242 (CA242), alpha-fetoprotein (AFP), beta-human chorionic gonadotropin (β-HCG), carcinoembryonic antigen (CEA), cancer antigen 199 (CA199), neuron-specific enolase (NSE), Ferritin, cancer antigen 153 (CA153), and human growth hormone (HGH) serum levels, and to compare the differences between the benign and malignant ovarian tumors. The correlation between tumor markers and clinicopathologic features for ovarian epithelial carcinoma was analyzed by χ 2 test. Spearman rank analysis showed the correlation between CA125 expression level and other tumor markers in epithelial ovarian cancer and the correlation between age and the above 10 tumor markers. Sensitivity, specificity, positive predictive value, negative predictive value, Youden index, and diagnostic efficiency were used to evaluate the diagnostic value of single tumor marker and the combination of tumor markers., Results: The levels of β-HCG, NSE, CA153, and CA125 in the epithelial ovarian cancer group were higher than those in the ovarian benign disease group. The level of NSE in the serum of patients with epithelial ovarian cancer was related to the clinical stage of patients. In addition, the levels of CA242, β-HCG, CEA, NSE, Ferritin, CA153 in the serum of patients with epithelial ovarian cancer were positively correlated with CA125 ( r s =0.497, P <0.001; r s =0.612, P <0.001; r s =0.358, P =0.003; r s =0.680, P <0.001; r s =0.322, P =0.009; r s =0.609, P <0.001, respectively), and the levels of β-HCG, Ferritin, CA153 were positively correlated with the patient's age ( r s =0.256, P =0.040; r s =0.325, P =0.008; r s =0.249, P =0.046, respectively). In the diagnosis of epithelial ovarian cancer, the sensitivity, Youden index, and diagnostic efficiency of CA125 detection alone were higher than the results of the other 9 separate detections. When CA153, CA199, CA242, Ferritin, and CEA were combined with CA125, the sensitivity of the combined detection of different combinations was higher than that of CA125 alone. The combined detection sensitivities of CA125+CEA and CA125+Ferritin+CEA were 89.2% and 90.8%, respectively, and the diagnostic efficiencies were both 84.1%, which were higher than those of other combinations. The Youden index of CA125+CEA joint detection was 0.616, which was higher than those of other combinations., Conclusions: CA125 has a high diagnostic value in the diagnosis of epithelial ovarian cancer. The detection of combined tumor markers in serum has higher sensitivity and specificity in epithelial ovarian cancer.