Clinical Laboratory of Integrative Medicine, The First Affiliated Hospital of Dalian Medical University, No.222 Zhongshan Road, Dalian, China.
Institute (College) of Integrative Medicine, Dalian Medical University, No.9 West Section Lvshun South Road, Dalian, China.
Sci Rep. 2021 Dec 8;11(1):23649. doi: 10.1038/s41598-021-03017-0.
Intrahepatic cholangiocarcinoma (CHOL) remains a rare malignancy, ranking as the leading lethal primary liver cancer worldwide. However, the biological functions of integrator complex subunit 8 (INTS8) in CHOL remain unknown. Thus, this research aimed to explore the potential role of INTS8 as a novel diagnostic or therapeutic target in CHOL. Differentially expressed genes (DEGs) in two Gene Expression Omnibus (GEO) datasets were obtained by the "RRA" package in R software. The "maftools" package was used to visualize the CHOL mutation data from The Cancer Genome Atlas (TCGA) database. The expression of INTS8 was detected by performing quantitative reverse transcription-PCR (qRT-PCR) and immunohistochemistry in cell lines and human samples. The association between subtypes of tumour-infiltrating immune cells (TIICs) and INTS8 expression in CHOL was determined by using CIBERSORT tools. We evaluated the correlations between INTS8 expression and mismatch repair (MMR) genes and DNA methyltransferases (DNMTs) in pan-cancer analysis. Finally, the pan-cancer prognostic signature of INTS8 was identified by univariate analysis. We obtained the mutation landscapes of an RRA gene set in CHOL. The expression of INTS8 was upregulated in CHOL cell lines and human CHOL samples. Furthermore, INTS8 expression was closely associated with a distinct landscape of TIICs, MMR genes, and DNMTs in CHOL. In addition, the high INTS8 expression group presented significantly poor outcomes, including overall survival (OS), disease-specific survival (DSS) and disease-free interval (DFI) (p < 0.05) in pan-cancer. INTS8 contributes to the tumorigenesis and progression of CHOL. Our study highlights the significant role of INTS8 in CHOL and pan-cancers, providing a valuable molecular target for cancer research.
肝内胆管癌（CHOL）仍然是一种罕见的恶性肿瘤，是全球导致原发性肝癌死亡的主要原因。然而，整合子复合物亚基 8（INTS8）在 CHOL 中的生物学功能尚不清楚。因此，本研究旨在探讨 INTS8 作为 CHOL 新型诊断或治疗靶点的潜力。通过 R 软件中的“RRA”包获得两个基因表达综合数据库（GEO）数据集的差异表达基因（DEGs）。使用“maftools”包可视化来自癌症基因组图谱（TCGA）数据库的 CHOL 突变数据。通过在细胞系和人类样本中进行定量逆转录-PCR（qRT-PCR）和免疫组织化学检测 INTS8 的表达。使用 CIBERSORT 工具确定 CHOL 中肿瘤浸润免疫细胞（TIIC）亚型与 INTS8 表达之间的关联。我们在泛癌分析中评估了 INTS8 表达与错配修复（MMR）基因和 DNA 甲基转移酶（DNMTs）之间的相关性。最后，通过单变量分析确定 INTS8 的泛癌预后特征。我们获得了 CHOL 中 RRA 基因集的突变图谱。INTS8 在 CHOL 细胞系和人类 CHOL 样本中表达上调。此外，INTS8 表达与 CHOL 中 TIICs、MMR 基因和 DNMTs 的独特景观密切相关。此外，INTS8 高表达组在泛癌中表现出明显较差的预后，包括总生存期（OS）、疾病特异性生存期（DSS）和无病间隔（DFI）（p<0.05）。INTS8 促进 CHOL 的肿瘤发生和进展。本研究强调了 INTS8 在 CHOL 和泛癌中的重要作用，为癌症研究提供了有价值的分子靶标。
