PDF(Pubmed)
Abstract：
UNASSIGNED: Hepatocellular carcinoma (HCC) is the most common primary malignancy of the liver, and becoming the third-leading cause of cancer-related mortality worldwide. Despite the immune checkpoint inhibitors and molecular targeted therapies have shown preferable efficacy in HCC, large number of HCC patients do not respond effectively to anti-PD-1 reagents. Besides, the accumulation of genetic mutations in cancer cells may lead to the therapy resistant. Hence, there are clinical gaps between genetic and transcriptomic biomarkers for the HCC treatment.
UNASSIGNED: To investigate the genetic mapping of liver cancer, targeted deep sequencing (TDS) and bioinformatics analysis were performed on hepatocellular carcinoma (HCC) tumor tissues and matched blood samples. Furthermore, copy number variants (CNVs) and Tumor mutation burden (TMB) were calculated. Immunohistochemistry was applied to determine the PD-L1 expression in HCC tumor tissues. Clinical characteristic, PD-L1 expression, and the TMB were analyzed in 32 HCC patients.
UNASSIGNED: This study indicated that the PD-L1 positive patients exhibited a lower TMB compared to the PD-L1 negative group, and PD-L1 positive patients were more likely to suffer from aggressive clinicopathologic features than PD-L1 negative patients. We also verified the top 30 mutated genes, including TP53, CTNNB1, KMT2D, AXIN1, ALK, and NOTCH1, in our dataset. Our results indicated that PD-L1 positive patients possessed more tumors with vascular invasion and advanced CCLC stage. Moreover, PD-L1 positive patients exhibited a lower TMB compared to the PD-L1 negative group.
UNASSIGNED: These findings could improve our understanding of the effects of immune checkpoint therapies on prognosis, and could facilitate the monitoring of somatic mutations in HCC.
UNASSIGNED: To investigate the genetic mapping of liver cancer, targeted deep sequencing (TDS) and bioinformatics analysis were performed on hepatocellular carcinoma (HCC) tumor tissues and matched blood samples. Furthermore, copy number variants (CNVs) and Tumor mutation burden (TMB) were calculated. Immunohistochemistry was applied to determine the PD-L1 expression in HCC tumor tissues. Clinical characteristic, PD-L1 expression, and the TMB were analyzed in 32 HCC patients.
UNASSIGNED: This study indicated that the PD-L1 positive patients exhibited a lower TMB compared to the PD-L1 negative group, and PD-L1 positive patients were more likely to suffer from aggressive clinicopathologic features than PD-L1 negative patients. We also verified the top 30 mutated genes, including TP53, CTNNB1, KMT2D, AXIN1, ALK, and NOTCH1, in our dataset. Our results indicated that PD-L1 positive patients possessed more tumors with vascular invasion and advanced CCLC stage. Moreover, PD-L1 positive patients exhibited a lower TMB compared to the PD-L1 negative group.
UNASSIGNED: These findings could improve our understanding of the effects of immune checkpoint therapies on prognosis, and could facilitate the monitoring of somatic mutations in HCC.
摘要：
■肝细胞癌（HCC）是肝脏最常见的原发性恶性肿瘤，并成为全球癌症相关死亡的第三大原因。尽管免疫检查点抑制剂和分子靶向治疗在HCC中显示出更好的疗效，大量HCC患者对抗PD-1试剂没有有效反应。此外,癌症细胞中基因突变的积累可能导致治疗耐药。因此，用于HCC治疗的遗传和转录组生物标志物之间存在临床差距。
■为了研究肝癌的遗传图谱，对肝细胞癌（HCC）肿瘤组织和匹配的血液样本进行靶向深度测序（TDS）和生物信息学分析。此外，计算拷贝数变体(CNV)和肿瘤突变负荷(TMB)。应用免疫组织化学检测PD-L1在HCC肿瘤组织中的表达。临床特征,PD-L1表达，并分析了32例HCC患者的TMB。
■这项研究表明，与PD-L1阴性组相比，PD-L1阳性患者的TMB较低，与PD-L1阴性患者相比，PD-L1阳性患者更有可能出现侵袭性临床病理特征。我们还验证了前30个突变基因，包括TP53，CTNNB1，KMT2D，AXIN1,ALK,和NOTCH1，在我们的数据集中。我们的结果表明，PD-L1阳性患者具有更多的血管浸润和晚期CCLC分期的肿瘤。此外，与PD-L1阴性组相比，PD-L1阳性患者表现出更低的TMB。
■这些发现可以提高我们对免疫检查点疗法对预后影响的理解。并且可以促进肝癌体细胞突变的监测。
■为了研究肝癌的遗传图谱，对肝细胞癌（HCC）肿瘤组织和匹配的血液样本进行靶向深度测序（TDS）和生物信息学分析。此外，计算拷贝数变体(CNV)和肿瘤突变负荷(TMB)。应用免疫组织化学检测PD-L1在HCC肿瘤组织中的表达。临床特征,PD-L1表达，并分析了32例HCC患者的TMB。
■这项研究表明，与PD-L1阴性组相比，PD-L1阳性患者的TMB较低，与PD-L1阴性患者相比，PD-L1阳性患者更有可能出现侵袭性临床病理特征。我们还验证了前30个突变基因，包括TP53，CTNNB1，KMT2D，AXIN1,ALK,和NOTCH1，在我们的数据集中。我们的结果表明，PD-L1阳性患者具有更多的血管浸润和晚期CCLC分期的肿瘤。此外，与PD-L1阴性组相比，PD-L1阳性患者表现出更低的TMB。
■这些发现可以提高我们对免疫检查点疗法对预后影响的理解。并且可以促进肝癌体细胞突变的监测。
