Project description:Gastric cancer (GC) is the fifth most common cancer and GC has a high mortality rate worldwide. Circular (circ) RNAs serve an important role in cancer. The present study aimed to investigate the expression level of hsa_circ_0060975 in gastric cancer (GC) and to determine the clinical pathological significance of hsa_circ_0060975 in patients with GC. Reverse transcription-quantitative PCR was used to detect expression level of hsa_circ_0060975 in 192 GC and adjacent non-cancerous gastric tissues, in GC cell lines (MKN-45, HGC27 and AGS) and a human gastric epithelium cell line (GES-1), as well as in plasma samples from 126 patients with GC and 92 healthy volunteers. All plasma and tissue samples of were obtained from The First Affiliated Hospital of Anhui Medical University (Hefei, China). The relationship between hsa_circ_0060975 expression and clinical pathological factors was analyzed using the χ2 test. The diagnostic value of hsa_circ_0060975 was analyzed using the receiver operating characteristic curve (ROC curve), while the Kaplan-Meier method was used to analyze the relationship of hsa_circ_0060975 expression with the survival of patients with GC as determined by log-rank tests. Univariate and multivariate Cox regression analyses were used to identify the prognostic factors, including hsa_circ_0060975 expression and clinical pathological factors. In addition, the potential function of hsa_circ_0060975 was evaluated via bioinformatics analysis. The expression level of hsa_circ_0060975 was higher in GC tissues compared with adjacent non-cancerous gastric tissues, GC cell lines compared with GES-1 and plasma samples from patients with GC compared with plasma samples from healthy volunteers. In addition, higher hsa_circ_0060975 expression was associated with histological grade, pathological stage and tumor (T) classification in GC tissues and plasma samples (P<0.05). The area under the ROC curves of hsa_circ_0060975, the combination with hsa_circ_0060975 and carcinoembryonic antigen (CEA) or CEA alone were 0.804 (sensitivity, 0.746; specificity, 0.783; P<0.001); 0.931 (sensitivity, 0.937; specificity, 0.870; P<0.001) and 0.924 (sensitivity, 0.937; sspecificity, 0.804; P<0.001) respectively. The Kaplan-Meier survival analysis revealed that the overall survival (OS) and disease-free survival (DFS) time of patients with higher hsa_circ_0060975 expression were shorter compared with those in patients with lower hsa_circ_0060975 expression. Univariate and multivariate Cox regression analyses in OS and DFS time determined that the expression level of hsa_circ_0060975, histological grade and pathological stage were independent prognostic factors for patients with GC. In addition, the bioinformatics analysis results suggested that the abnormal expression of hsa_circ_0060975 may serve an important role in tumorigenesis. Hence, hsa_circ_0060975 expression may be an independent prognostic factor for patients with GC and may be a potential marker for biological malignancy.

Project description:Background - Hepatocellular carcinomas (HCCs) are heterogeneous tumors with respect to etiology, cell of origin and biology. The course of the disease is unpredictable and is in part dependent on the tumor microenvironment. One of the microenvironmental factors is hypoxia, which is known to promote aggressiveness in other malignant tumors. We hypothesized that certain regions in HCC exist with chronic hypoxia and a characteristic gene expression pattern. Moreover, during the development of HCC there is an important contribution of this chronic hypoxia on prognosis via this gene expression. Until now, most research has been performed in acute hypoxic models (< 24 hours). Methods – Human hepatoblastoma cells HepG2 were cultured in either normoxic (20% O2) or hypoxic (2% O2) conditions for 72 hrs, the time it takes to adapt to chronic hypoxia. After 3 days the cells were harvested and analyzed by microarray technology. The highly significant differentially expressed genes were selected and used to assess the clinical value of our in vitro chronic hypoxia gene signature in four published patient studies. Three of these independent microarray studies on HCC patients were used as training sets to determine a minimal prognostic gene set and one study was used for validation. Gene expression analysis and correlation with clinical outcome was assessed with the bioinfomatic method of Goeman et al (). Results – In the HepG2 cells, 3592 genes were differentially expressed in cells cultured at 2% oxygen for 72 hrs. Out of these, 265 showed a high significant change (2-fold change and p=0.0001). The level of gene expression after 72 hrs was different from the acute hypoxic response (during the first 24 hours) and represented chronicity. Using computational methods we identified 7 out of the 265 highly significant genes that showed correlation with prognosis in all three different training sets and this was independently validated in a 4th dataset. With our approach we could include the largest number of HCC patients in one single study. Conclusion – We identified a 7-gene signature, which is associated with chronic hypoxia and predicts prognosis in patients with HCC. In the future this signature could be used as a diagnostic tool. In addition, chronic hypoxia gene expression information can be used in the search for new therapeutic targets. Two conditions were compared and each sample has a biological replicate. Samples are hybridized in dye-swap, resulting in 4 hybridizations.

Project description:Background - Hepatocellular carcinomas (HCCs) are heterogeneous tumors with respect to etiology, cell of origin and biology. The course of the disease is unpredictable and is in part dependent on the tumor microenvironment. One of the microenvironmental factors is hypoxia, which is known to promote aggressiveness in other malignant tumors. We hypothesized that certain regions in HCC exist with chronic hypoxia and a characteristic gene expression pattern. Moreover, during the development of HCC there is an important contribution of this chronic hypoxia on prognosis via this gene expression. Until now, most research has been performed in acute hypoxic models (< 24 hours). Methods – Human hepatoblastoma cells HepG2 were cultured in either normoxic (20% O2) or hypoxic (2% O2) conditions for 72 hrs, the time it takes to adapt to chronic hypoxia. After 3 days the cells were harvested and analyzed by microarray technology. The highly significant differentially expressed genes were selected and used to assess the clinical value of our in vitro chronic hypoxia gene signature in four published patient studies. Three of these independent microarray studies on HCC patients were used as training sets to determine a minimal prognostic gene set and one study was used for validation. Gene expression analysis and correlation with clinical outcome was assessed with the bioinfomatic method of Goeman et al (). Results – In the HepG2 cells, 3592 genes were differentially expressed in cells cultured at 2% oxygen for 72 hrs. Out of these, 265 showed a high significant change (2-fold change and p=0.0001). The level of gene expression after 72 hrs was different from the acute hypoxic response (during the first 24 hours) and represented chronicity. Using computational methods we identified 7 out of the 265 highly significant genes that showed correlation with prognosis in all three different training sets and this was independently validated in a 4th dataset. With our approach we could include the largest number of HCC patients in one single study. Conclusion – We identified a 7-gene signature, which is associated with chronic hypoxia and predicts prognosis in patients with HCC. In the future this signature could be used as a diagnostic tool. In addition, chronic hypoxia gene expression information can be used in the search for new therapeutic targets.

Dataset Information

Highly expressed RPLP2 inhibits ferroptosis to promote hepatocellular carcinoma progression and predicts poor prognosis

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets