The Consumption of Cholesterol-Enriched Diets Conditions the Development of a Subtype of HCC with High Aggressiveness and Poor Prognosis.
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ABSTRACT:
SUBMITTER: Simoni-Nieves A
PROVIDER: S-EPMC8038696 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Prothymosin-α (PTMA), a nuclear protein, is strikingly associated with unfavorable clinical outcomes in many cancers. However, no information about its clinical relevance in glioma was available. Therefore in the present study, we evaluated the prognostic utility of this protein in a cohort of 81 glioma patients. The PTMA expression was assessed by immunohistochemical analysis, quantitative PCR, and Western blotting. Furthermore, the association of PTMA with clinicopathological features and molecular alterations were assessed in the patient cohort and validated in multiomics datasets, The Cancer Genome Atlas (TCGA; n=667) and Chinese Glioma Genome Atlas (CGGA; n=1013). We observed an increase in PTMA expression with increasing histological grades of this malignancy. PTMA immunostaining also displayed a strong positive association with the MIB-1 index. Univariate analysis revealed a superior prognostic value of PTMA to predict overall survival (OS) as compared with the routinely used markers (p53, isocitrate dehydrogenase (IDH) 1 (IDH1), α-thalassemia/intellectual disability syndrome X-linked (ATRX), and Ki-67). Interestingly, in Cox regression analysis it emerged as an independent predictor of OS (hazard ratio (HR) = 13.71, 95% CI = 5.96-31.52, P<0.0001). Thus, our results demonstrate the potential prognostic utility of PTMA in glioma which may prove useful in the management of this deadly malignancy.
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Project description:This study aimed to investigate the prognostic value and molecular mechanism of DDX39 and its effector SNAIL in melanoma. First, overexpression of DDX39 in melanoma, which was identified by database analysis, was further validated in patient tissues. Cell growth, cell cycle, cell migration, and cell invasion assays were then performed to evaluate the effects of downregulated DDX39 on the melanoma cell proliferation and aggressiveness. The same approaches were also used to reveal the cooperation of the transcription factor SNAIL with DDX39 to promote the aggressiveness of melanoma cells. We found that the expression of DDX39 was significantly upregulated in melanoma tissue compared to pigmented nevus tissue, and it was positively correlated with the clinical stage defined by the American Joint Committee on Cancer (AJCC) and the prognosis. Downregulation of DDX39 in melanoma cells was found to significantly inhibit cell proliferation, increase G2/M cell cycle arrest, enhance caspase-mediated cell apoptosis, and suppress cell invasion and migration. In addition, we demonstrated that the overexpression of SNAIL could restore the cell growth and aggressiveness impaired by DDX39 RNA interference. Immunohistochemical staining also showed a positive correlation between DDX39 overexpression and SNAIL overexpression in melanoma tissues, suggesting that SNAIL is one of the effectors activated by DDX39. In summary, the overexpression of DDX39 and SNAIL was positively related to the poor prognosis of melanoma patients and the increased aggressiveness of melanoma cells. Our study provides valuable evidence regarding the prognostic value of DDX39 and SNAIL as well as their potential as novel therapeutic targets for treating melanoma patients.
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Project description:BACKGROUND:ZW10 interactor was recently reported to correlate with human cancers. However, the prognostic value of ZW10 interactor in hepatocellular carcinoma was not reported. METHODS:The expression level of ZW10 interactor was evaluated by Western blot and immunohistochemistry using tissue microarray. In the present study, we used 5 pairs of hepatocellular carcinoma and peritumoral frozen tissues for Western blot, and 70 paired paraffin-embedded hepatocellular carcinoma and peritumoral tissues as expression pattern cohort (cohort 1), and 280 paraffin-embedded hepatocellular carcinoma tissues were used as prognostic cohort (cohort 2). The integral optic density representing the expression level of ZW10 interactor in each tissue sample, was calculated using Image-Pro Plus. The integral optic density was added to the X-tile software for calculating the outcome-based cut point. Kaplan-Meier and Cox regression were used to evaluate the prognostic values. RESULTS:The expression level ZW10 interactor was decreased in hepatocellular carcinoma tissues in 85.7% (60/70) of the cases compared to the corresponding peritumoral tissues evaluated by immunohistochemistry. Similar result was obtained by Western blot analysis using frozen tissue. Expression of ZW10 interactor was closely correlated with age ( P = .0001) and liver cirrhosis in cohort 1 and tumor node metastasis ( P = .018), tumor size ( P = .005), and vascular invasion ( P = .022) in cohort 2 based on ?2 analyses. Survival analyses indicated that patients with hepatocellular carcinoma having low ZW10 interactor expression had a shorter overall survival time and time to recurrence compared to cases with high ZW10 interactor expression in the prognostic cohort ( P < .0001 for both overall survival and time to recurrence ). Univariate and multivariate Cox analyses indicated that ZW10 interactor was an independent prognostic factor for overall survival ( P = .033). CONCLUSIONS:The present study clearly showed that ZW10 interactor was frequently decreased in hepatocellular carcinoma compared to nontumoral liver tissues, and ZW10 interactor could serve as a potential prognostic marker in patients with hepatocellular carcinoma after surgery.
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