PDF(Pubmed)
Abstract：
UNASSIGNED: Pancreatic adenocarcinoma (PAAD) is characterized by lower immunogenicity with a poor response rate to immune checkpoint inhibitors (ICIs) and exhibits the poorest prognosis of all solid tumors, which results in the highest tumor-related mortality among malignancies. However, the underlying mechanisms are poorly understood. In addition, diverse carbohydrate sulfotransferases (CHSTs), which are involved in the sulfation process of these structures, play an important role in the metastatic spread of tumor cells. Aberrant glycosylation is beginning to emerge as an influencing factor in tumor immunity and immunotherapy. Therefore, it might serve as a biomarker of the immunotherapeutic response in tumors. The purpose of the study was to evaluate the role of CHST12 in PAAD prognosis and its relevance to the immunotherapeutic response.
UNASSIGNED: A comprehensive investigation of the interactions between CHST12 expression and the immune microenvironment as well as the clinical significance of CHST12 in PAAD was conducted. Data derived from the Cancer Genome Atlas (TCGA) database were analyzed using univariate and multivariate approaches, the Tumor Immune Estimation Resource (TIMER), and Tumor Immune Dysfunction and Exclusion (TIDE) algorithms. Publicly available datasets were analyzed in this study. These data can be found on websites such as http://www.xiantao.love and https://www.proteinatlas.org. An assessment of the predictive value of CHST12 for PAAD prognosis was conducted using univariate and multivariate Cox regression analysis, Kaplan-Meier analysis, and nomograms. The TIMER algorithm calculates the proportions of six types of immune cells. The TIDE algorithm was used to indicate the characteristics of tumors that respond to ICI therapy.
UNASSIGNED: The mRNA and protein levels of CHST12 showed the opposite trend. CHST12 mRNA expression was significantly upregulated in PAAD. According to Cox regression analysis, CHST12 RNA expression acts as a protective factor for overall survival [hazard ratio (HR), 0.617, P < 0.04]. Functional annotation indicated that CHST12-associated differentially expressed genes (DEGs) were related to the signaling activity of receptor tyrosine kinases and the regulation of ubiquitin-protein transferase. These are usually involved in tumor development and may be related to the treatment responses of immune checkpoint inhibitors (ICIs). There was significantly higher CHST12 mRNA expression in PAAD samples than in non-malignant samples.
UNASSIGNED: In PAAD, elevated CHST12 mRNA expression might regulate immune cell infiltration into the tumor microenvironment (TME) and may predict clinical outcomes.
UNASSIGNED: A comprehensive investigation of the interactions between CHST12 expression and the immune microenvironment as well as the clinical significance of CHST12 in PAAD was conducted. Data derived from the Cancer Genome Atlas (TCGA) database were analyzed using univariate and multivariate approaches, the Tumor Immune Estimation Resource (TIMER), and Tumor Immune Dysfunction and Exclusion (TIDE) algorithms. Publicly available datasets were analyzed in this study. These data can be found on websites such as http://www.xiantao.love and https://www.proteinatlas.org. An assessment of the predictive value of CHST12 for PAAD prognosis was conducted using univariate and multivariate Cox regression analysis, Kaplan-Meier analysis, and nomograms. The TIMER algorithm calculates the proportions of six types of immune cells. The TIDE algorithm was used to indicate the characteristics of tumors that respond to ICI therapy.
UNASSIGNED: The mRNA and protein levels of CHST12 showed the opposite trend. CHST12 mRNA expression was significantly upregulated in PAAD. According to Cox regression analysis, CHST12 RNA expression acts as a protective factor for overall survival [hazard ratio (HR), 0.617, P < 0.04]. Functional annotation indicated that CHST12-associated differentially expressed genes (DEGs) were related to the signaling activity of receptor tyrosine kinases and the regulation of ubiquitin-protein transferase. These are usually involved in tumor development and may be related to the treatment responses of immune checkpoint inhibitors (ICIs). There was significantly higher CHST12 mRNA expression in PAAD samples than in non-malignant samples.
UNASSIGNED: In PAAD, elevated CHST12 mRNA expression might regulate immune cell infiltration into the tumor microenvironment (TME) and may predict clinical outcomes.
摘要：
■胰腺腺癌（PAAD）的特征是免疫原性较低，对免疫检查点抑制剂（ICI）的反应率差，并且在所有实体瘤中预后最差，导致恶性肿瘤中肿瘤相关死亡率最高。然而,潜在的机制知之甚少。此外,不同的碳水化合物磺基转移酶（CHSTs），参与这些结构的硫酸化过程，在肿瘤细胞的转移扩散中起重要作用。异常糖基化开始成为肿瘤免疫和免疫治疗的影响因素。因此,它可能作为肿瘤免疫治疗反应的生物标志物。该研究的目的是评估CHST12在PAAD预后中的作用及其与免疫治疗反应的相关性。
■对CHST12表达与免疫微环境之间的相互作用以及CHST12在PAAD中的临床意义进行了全面研究。使用单变量和多变量方法分析来自癌症基因组图谱（TCGA）数据库的数据，肿瘤免疫评估资源(TIMER)，和肿瘤免疫功能障碍和排除（TIDE）算法。在这项研究中分析了公开可用的数据集。这些数据可以在http://www等网站上找到。仙桃。爱和https://www.proteinatlas.org.使用单变量和多变量Cox回归分析评估CHST12对PAAD预后的预测价值。Kaplan-Meier分析,和列线图。TIMER算法计算六种类型的免疫细胞的比例。TIDE算法用于指示响应ICI治疗的肿瘤的特征。
■CHST12的mRNA和蛋白水平呈相反的趋势。CHST12mRNA在PAAD中表达显著上调。根据Cox回归分析，CHST12RNA表达作为总体生存的保护因素[风险比（HR），0.617,P<0.04]。功能注释表明，CHST12相关差异表达基因（DEGs）与受体酪氨酸激酶的信号活性和泛素蛋白转移酶的调节有关。这些通常与肿瘤发展有关，可能与免疫检查点抑制剂（ICI）的治疗反应有关。PAAD样品中的CHST12mRNA表达显著高于非恶性样品。
■在PAAD中，升高的CHST12mRNA表达可能调节免疫细胞浸润到肿瘤微环境(TME),并可能预测临床结局.
■对CHST12表达与免疫微环境之间的相互作用以及CHST12在PAAD中的临床意义进行了全面研究。使用单变量和多变量方法分析来自癌症基因组图谱（TCGA）数据库的数据，肿瘤免疫评估资源(TIMER)，和肿瘤免疫功能障碍和排除（TIDE）算法。在这项研究中分析了公开可用的数据集。这些数据可以在http://www等网站上找到。仙桃。爱和https://www.proteinatlas.org.使用单变量和多变量Cox回归分析评估CHST12对PAAD预后的预测价值。Kaplan-Meier分析,和列线图。TIMER算法计算六种类型的免疫细胞的比例。TIDE算法用于指示响应ICI治疗的肿瘤的特征。
■CHST12的mRNA和蛋白水平呈相反的趋势。CHST12mRNA在PAAD中表达显著上调。根据Cox回归分析，CHST12RNA表达作为总体生存的保护因素[风险比（HR），0.617,P<0.04]。功能注释表明，CHST12相关差异表达基因（DEGs）与受体酪氨酸激酶的信号活性和泛素蛋白转移酶的调节有关。这些通常与肿瘤发展有关，可能与免疫检查点抑制剂（ICI）的治疗反应有关。PAAD样品中的CHST12mRNA表达显著高于非恶性样品。
■在PAAD中，升高的CHST12mRNA表达可能调节免疫细胞浸润到肿瘤微环境(TME),并可能预测临床结局.
