PDF(Pubmed)
Abstract：
UNASSIGNED: Hepatocellular carcinoma (HCC) is one of the most common malignant tumors originating from the digestive system. Tertiary lymphoid structures (TLS), non-lymphoid tissues outside of the lymphoid organs, are closely connected to chronic inflammation and tumorigenesis. However, the detailed relationship between TLS and HCC prognosis remained unclear. In this study, we aimed to construct a TLS-related gene signature for predicting the prognosis of HCC patients.
UNASSIGNED: The Cancer Genome Atlas (TCGA) clinical data from 369 HCC tissues and 50 normal liver tissues were utilized to examine the differential expression of TLS-related genes. Based on least absolute shrinkage and selection operator (LASSO) Cox regression analysis, the prognostic model was constructed using the TCGA cohort and validated in the GSE14520 cohort and International Cancer Genome Consortium (ICGC) cohort. The Kaplan-Meier (KM) and receiver operating characteristic (ROC) curves were employed to validate the predictive ability of the prognostic model. Furthermore, Cox regression analysis was applied to identify whether the TLS score could be employed as an independent prognosis factor. A nomogram was developed to predict the survival probability of HCC patients. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were performed for TLS-related genes. Genetic mutation analysis, the CIBERSORT algorithm, and single-sample gene set enrichment analysis (ssGSEA) were used to assess the tumor mutation landscape and immune infiltration. Finally, the role of the TLS score in HCC therapy was investigated.
UNASSIGNED: Six genes were included in the construction of our prognostic model (CETP, DNASE1L3, PLAC8, SKAP1, C7, and VNN2), and we validated its accuracy. Survival analysis showed that patients in the high-TLS score group had a significantly better overall survival than those in the low-TLS score group. Univariate, multivariate Cox regression analysis and the establishment of a nomogram indicated that the TLS score could independently function as a potential prognostic marker. A significant association between TLS score and immunity was revealed by an analysis of gene alterations and immune cell infiltration. In addition, two subtypes of the TLS score could accurately predict the effectiveness of sorafenib, transcatheter arterial chemoembolization (TACE), and immunotherapy in HCC patients.
UNASSIGNED: In this research, we conducted and validated a prognostic model associated with TLS that may be helpful for predicting clinical outcomes and treatment responsiveness for HCC patients.
UNASSIGNED: The Cancer Genome Atlas (TCGA) clinical data from 369 HCC tissues and 50 normal liver tissues were utilized to examine the differential expression of TLS-related genes. Based on least absolute shrinkage and selection operator (LASSO) Cox regression analysis, the prognostic model was constructed using the TCGA cohort and validated in the GSE14520 cohort and International Cancer Genome Consortium (ICGC) cohort. The Kaplan-Meier (KM) and receiver operating characteristic (ROC) curves were employed to validate the predictive ability of the prognostic model. Furthermore, Cox regression analysis was applied to identify whether the TLS score could be employed as an independent prognosis factor. A nomogram was developed to predict the survival probability of HCC patients. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were performed for TLS-related genes. Genetic mutation analysis, the CIBERSORT algorithm, and single-sample gene set enrichment analysis (ssGSEA) were used to assess the tumor mutation landscape and immune infiltration. Finally, the role of the TLS score in HCC therapy was investigated.
UNASSIGNED: Six genes were included in the construction of our prognostic model (CETP, DNASE1L3, PLAC8, SKAP1, C7, and VNN2), and we validated its accuracy. Survival analysis showed that patients in the high-TLS score group had a significantly better overall survival than those in the low-TLS score group. Univariate, multivariate Cox regression analysis and the establishment of a nomogram indicated that the TLS score could independently function as a potential prognostic marker. A significant association between TLS score and immunity was revealed by an analysis of gene alterations and immune cell infiltration. In addition, two subtypes of the TLS score could accurately predict the effectiveness of sorafenib, transcatheter arterial chemoembolization (TACE), and immunotherapy in HCC patients.
UNASSIGNED: In this research, we conducted and validated a prognostic model associated with TLS that may be helpful for predicting clinical outcomes and treatment responsiveness for HCC patients.
摘要：
■肝细胞癌（HCC）是起源于消化系统的最常见的恶性肿瘤之一。三级淋巴结构（TLS），淋巴器官外的非淋巴组织,与慢性炎症和肿瘤发生密切相关。然而,TLS与HCC预后之间的详细关系尚不清楚.在这项研究中,我们的目的是构建一个TLS相关的基因标记来预测HCC患者的预后.
■使用来自369个HCC组织和50个正常肝组织的癌症基因组图谱（TCGA）临床数据来检查TLS相关基因的差异表达。基于最小绝对收缩和选择算子(LASSO)Cox回归分析，使用TCGA队列构建预后模型,并在GSE14520队列和国际癌症基因组联盟(ICGC)队列中进行验证.采用Kaplan-Meier（KM）和受试者工作特征（ROC）曲线来验证预后模型的预测能力。此外，Cox回归分析用于确定TLS评分是否可以用作独立的预后因素。建立列线图来预测HCC患者的生存概率。对TLS相关基因进行基因本体论(GO)和京都基因和基因组百科全书(KEGG)途径。基因突变分析,CIBERSORT算法，和单样本基因组富集分析（ssGSEA）用于评估肿瘤突变景观和免疫浸润。最后,研究了TLS评分在HCC治疗中的作用。
■我们的预后模型的构建中包含了六个基因（CETP，DNASE1L3、PLAC8、SKAP1、C7和VNN2),我们验证了它的准确性。生存分析显示，高TLS评分组患者的总生存率明显优于低TLS评分组患者。单变量,多变量Cox回归分析和列线图的建立表明，TLS评分可以独立地用作潜在的预后标志物。通过分析基因改变和免疫细胞浸润，揭示了TLS评分与免疫力之间的显着关联。此外,两种亚型的TLS评分可以准确预测索拉非尼的有效性，经导管动脉化疗栓塞术(TACE),肝癌患者的免疫治疗。
■在这项研究中，我们进行并验证了与TLS相关的预后模型,该模型可能有助于预测HCC患者的临床结局和治疗反应性.
■使用来自369个HCC组织和50个正常肝组织的癌症基因组图谱（TCGA）临床数据来检查TLS相关基因的差异表达。基于最小绝对收缩和选择算子(LASSO)Cox回归分析，使用TCGA队列构建预后模型,并在GSE14520队列和国际癌症基因组联盟(ICGC)队列中进行验证.采用Kaplan-Meier（KM）和受试者工作特征（ROC）曲线来验证预后模型的预测能力。此外，Cox回归分析用于确定TLS评分是否可以用作独立的预后因素。建立列线图来预测HCC患者的生存概率。对TLS相关基因进行基因本体论(GO)和京都基因和基因组百科全书(KEGG)途径。基因突变分析,CIBERSORT算法，和单样本基因组富集分析（ssGSEA）用于评估肿瘤突变景观和免疫浸润。最后,研究了TLS评分在HCC治疗中的作用。
■我们的预后模型的构建中包含了六个基因（CETP，DNASE1L3、PLAC8、SKAP1、C7和VNN2),我们验证了它的准确性。生存分析显示，高TLS评分组患者的总生存率明显优于低TLS评分组患者。单变量,多变量Cox回归分析和列线图的建立表明，TLS评分可以独立地用作潜在的预后标志物。通过分析基因改变和免疫细胞浸润，揭示了TLS评分与免疫力之间的显着关联。此外,两种亚型的TLS评分可以准确预测索拉非尼的有效性，经导管动脉化疗栓塞术(TACE),肝癌患者的免疫治疗。
■在这项研究中，我们进行并验证了与TLS相关的预后模型,该模型可能有助于预测HCC患者的临床结局和治疗反应性.
