Gastric cancer is one of the most common and lethal cancers worldwide. However, despite its clinical importance, the regulatory mechanisms involved in the aggressiveness of this cancer are still poorly understood. A better understanding of the biology, genetics and molecular mechanisms of gastric cancer would be useful in developing novel targeted approaches for treating this disease. In this study we used protein-protein interaction networks and cluster analysis to comprehensively investigate the cellular pathways involved in gastric cancer. A primary immunodeficiency pathway, focal adhesion, ECM-receptor interactions and the metabolism of xenobiotics by cytochrome P450 were identified as four important pathways associated with the progression of gastric cancer. The genes in these pathways, e.g., ZAP70, IGLL1, CD79A, COL6A3, COL3A1, COL1A1, CYP2C18 and CYP2C9, may be considered as potential therapeutic targets for gastric cancer.
Retinoic acid has been recognised as a pivotal compound in cell differentiation, proliferation and malignant transformation (Shyu et al., 1995;Tanaka and De Luca, 2009). Retinoids are natural and synthetic derivatives of retinol (vitamin A). The naturally occuring retinoids, all-trans retinoic acid, 9-cis retinoic acid and 13-cis retinoic acid, are generated from diet-derived retinol. Retinoids are ligands of cellular receptors of retinoic acid, including retinoic acid receptors (RARs) and retinoid X receptors (RXRs) who are members of the steroid and thyroid hormone receptor superfamily (Evans, 1998;Sun and Lotan, 2002). Each subtype of both retinoid receptor classes (RARa, RARβ, RARγ and RXRa, RXRβ, RXRγ respectively) is encoded by separate genes. Multiple isoforms of receptor subtypes exist as a result of
Background The tumor-promoting role of tumor microenvironment (TME) in colorectal cancer has been widely investigated in cancer biology. Cancer-associated fibroblasts (CAFs), as the main stromal component in TME, play an important role in promoting tumor progression and metastasis. Hence, we explored the crosstalk between CAFs and microenvironment in the pathogenesis of colorectal cancer in order to provide basis for precision therapy. Methods We integrated spatial transcriptomics (ST) and bulk-RNA sequencing datasets to explore the functions of CAFs in the microenvironment of CRC. In detail, single sample gene set enrichment analysis (ssGSEA), gene set variation analysis (GSVA), pseudotime analysis and cell proportion analysis were utilized to identify the cell types and functions of each cell cluster. Immunofluorescence and immunohistochemistry were applied to confirm the results based on bioinformatics analysis. Results We profiled the tumor heterogeneity landscape and identified two distinct types of CAFs, which myo-cancer-associated fibroblasts (mCAFs) is associated with myofibroblast-like cells and inflammatory-cancer-associated fibroblasts (iCAFs) is related to immune inflammation. When we carried out functional analysis of two types of CAFs, we uncovered an extensive crosstalk between iCAFs and stromal components in TME to promote tumor progression and metastasis. Noticeable, some anti-tumor immune cells such as NK cells, monocytes were significantly reduced in iCAFs-enriched cluster. Then, ssGSEA analysis results showed that iCAFs were related to EMT, lipid metabolism and bile acid metabolism etc. Besides, when we explored the relationship of chemotherapy and microenvironment, we detected that iCAFs influenced immunosuppressive cells and lipid metabolism reprogramming in patient who underwent chemotherapy. Additionally, we identified the clinical role of iCAFs through a public database and confirmed it were related to poor prognosis. Conclusions In summary, we identified two types of CAFs using integrated data and explored their functional significance in TME. This in-depth understanding of CAFs in microenvironment may help us to elucidate its cancer-promoting functions and offer hints for therapeutic studies.
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Objectives Free portal pressure measurement is a reliable method for assessment of portal pressure in patients with cirrhosis. Intrahepatic circulatory time analysis of a sonographic contrast agent can assess liver fibrosis and its severity. The purposes of this pilot study were to assess the correlation between the intrahepatic circulatory time and free portal pressure and to assess whether intrahepatic circulatory time analysis can be used to predict portal venous pressure severity. Methods The intrahepatic circulatory time and free portal pressure were measured in 31 patients with hepatitis B virus–related liver disease. Pearson correlation analysis was used to assess the correlation between the intrahepatic circulatory time and free portal pressure. Results The hepatic vein–hepatic artery interval times were significantly shorter in the portal hypertension group than the non–portal hypertension group (mean ± SD, 8.26 ± 1.94 and 13.83 ± 1.17 seconds, respectively; P < .001). The portal vein–hepatic artery interval times were significantly longer in the portal hypertension group than the nonportal hypertension group (13.13 ± 2.25 and 7.25 ± 1.81 seconds; P < .001). Considering the whole patient population, there were statistically significant correlations between free portal pressure and the hepatic vein–hepatic artery interval time (r = −0.900; P < .001) and portal vein–hepatic artery interval time (r = 0.808; P < .001). In patients with portal hypertension, there was a statistically significant correlation between free portal pressure and the hepatic vein–hepatic artery interval time (r = −0.804; P = .009) and a weak correlation between free portal pressure and the portal vein–hepatic artery interval time (r = 0.506; P = .036). Conclusions Intrahepatic circulatory time measurement is correlated with free portal pressure and has the potential capability to evaluate portal pressure noninvasively in patients with hepatitis B virus–related liver disease.
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