The role of CD4 1 cytotoxic T cells (CTLs) in hepatocellular carcinoma (HCC) remains obscure. This study characterized CD41 CTLs in HCC patients and further elucidated the associations between CD41 CTLs and HCC disease progression. In all, 547 HCC patients, 44 chronic hepatitis B (CHB) patients, 86 liver cirrhosis (LC) patients, and 88 healthy individuals were enrolled in the study. CD41 CTLs were defined by flow cytometry, immunohistochemistry, and lytic granule exocytosis assays. A multivariate analysis of prognostic factors for overall survival was performed using the Cox proportional hazards model. Circulating and liver-infiltrating CD41 CTLs were found to be significantly increased in HCC patients during early stage disease, but decreased in progressive stages of HCC. This loss of CD41 CTLs was significantly correlated with high mortality rates and reduced survival time of HCC patients. In addition, the proliferation, degranulation, and production of granzyme A, granzyme B, and perforin of CD4 1 CTLs were inhibited by the increased forkhead/winged helix transcription factor (FoxP3 1 ) regulatory T cells in these HCC patients. Further analysis showed that both circulating and tumor-infiltrating CD4
An increasing number of evidences indicate microbes are implicated in human physiological mechanisms, including complicated disease pathology. Some microbes have been demonstrated to be associated with diverse important human diseases or disorders. Through investigating these disease-related microbes, we can obtain a better understanding of human disease mechanisms for advancing medical scientific progress in terms of disease diagnosis, treatment, prevention, prognosis and drug discovery. Based on the known microbe-disease association network, we developed a semi-supervised computational model of Laplacian Regularized Least Squares for Human Microbe–Disease Association (LRLSHMDA) by introducing Gaussian interaction profile kernel similarity calculation and Laplacian regularized least squares classifier. LRLSHMDA reached the reliable AUCs of 0.8909 and 0.7657 based on the global and local leave-one-out cross validations, respectively. In the framework of 5-fold cross validation, average AUC value of 0.8794 +/−0.0029 further demonstrated its promising prediction ability. In case studies, 9, 9 and 8 of top-10 predicted microbes have been manually certified to be associated with asthma, colorectal carcinoma and chronic obstructive pulmonary disease by published literature evidence. Our proposed model achieves better prediction performance relative to the previous model. We expect that LRLSHMDA could offer insights into identifying more promising human microbe-disease associations in the future.
BackgroundSOX9 as a member of the SOX (SRY [sex determining region Y] box) gene superfamily has been previously demonstrated to be a proto-oncogene in a variety of malignancies. However, the clinical significance of SOX9 expression in hepatocellular carcinoma (HCC) remains unclear. The aim of this study was to investigate the expression of SOX9 in HCC and determine its correlation with tumor progression and prognosis.MethodsOne-hundred and thirty HCC patients who had undergone curative liver resection were selected and immunohistochemistry, Western blotting, and quantitative real time polymerase chain reaction (Q-PCR) were performed to analyze SOX9 expression in the respective tumors.ResultsImmunohistochemistry, Western blotting, and Q-PCR consistently confirmed SOX9 overexpression in HCC tissues compared with their adjacent nonneoplastic tissues (P ≪ 0.01). Additionally, immunostaining showed more SOX9 positive cells in the higher tumor stage (T3 ~ 4) and tumor grade (G3) than in the lower tumor stage (T1 ~ 2, P = 0.03) and tumor grade (G1 ~ 2, P = 0.01), respectively. Moreover, HCC patients with high SOX9 expression were significantly associated with lower 5-year overall survival (P ≪ 0.01) and lower 5-year disease-free survival (P ≪ 0.01), respectively. The Cox proportional hazards model further showed that SOX9 over-expression was an independent poor prognostic factor for both 5-year disease-free survival (hazards ratio [HR] = 2.621, 95% confidence interval[CI] = 1.548-5.829, P = 0.01) and 5-year overall survival (HR = 3.825, CI = 1.638-7.612, P = 0.003) in HCC.ConclusionOur data suggest for the first time that the overexpression of SOX9 protein in HCC tissues is of predictive value on tumor progression and poor prognosis.Virtual slidesThe virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/9029740396926377.
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