Department of Surgery, Kyushu University Beppu Hospital, Beppu, Japan.
Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, Suita, Japan.
Anticancer Res. 2022 Oct;42(10):4701-4706. doi: 10.21873/anticanres.15974.
BACKGROUND/AIM: Alternative splicing plays a vital role in cancer development and progression. The splicing C complex is involved in alternative splicing. However, the role of PRKR-interacting protein 1 (PRKRIP1), a component of the splicing C complex, in colorectal cancer (CRC) remains unclear. This study aimed to determine the clinicopathological, biological and prognostic significance of PRKRIP1 expression in CRC.
We used a bioinformatics approach to screen for oncogenes using The Cancer Genome Atlas (TCGA) and Cancer Cell Line Encyclopedia (CCLE) datasets and identified PRKRIP1 as a driver gene on chromosome 7q. The mRNA expression of PRKRIP1 was measured using reverse transcription-quantitative PCR in 165 surgically resected CRC samples in our hospital, and its localization was determined using immunohistochemical staining. Gene Set Enrichment Analysis (GSEA) was performed using TCGA dataset.
High PRKRIP1 expression was significantly associated with poor prognosis in both the samples and TCGA dataset. A positive correlation was observed between copy number variation and PRKRIP1 expression in TCGA and CCLE datasets, and the frequency of PRKRIP1 mutations was less than 5%. Immunohistochemistry revealed that PRKRIP1 was located in the cytoplasm of tumor cells. GSEA revealed that PRKRIP1 expression was correlated with apoptosis-related gene sets.
PRKRIP1 overexpression may be a poor prognostic biomarker for CRC. Although it is known that PRKRIP1, a spliceosome factor, is essential for splicing, we now revealed the way by which its expression accelerates CRC progression.
背景/目的：可变剪接在癌症的发生和发展中起着至关重要的作用。剪接 C 复合物参与可变剪接。然而，剪接 C 复合物的一个组成部分 PRKR 相互作用蛋白 1（PRKRIP1）在结直肠癌（CRC）中的作用尚不清楚。本研究旨在确定 PRKRIP1 在 CRC 中的表达的临床病理、生物学和预后意义。
我们使用生物信息学方法筛选了来自癌症基因组图谱（TCGA）和癌症细胞系百科全书（CCLE）数据集的癌基因，发现 PRKRIP1 是染色体 7q 上的驱动基因。使用反转录定量 PCR 测量了我们医院 165 例手术切除的 CRC 样本中 PRKRIP1 的 mRNA 表达，并使用免疫组织化学染色确定了其定位。使用 TCGA 数据集进行基因集富集分析（GSEA）。
高 PRKRIP1 表达与样本和 TCGA 数据集的预后不良显著相关。在 TCGA 和 CCLE 数据集中观察到拷贝数变异与 PRKRIP1 表达之间存在正相关，并且 PRKRIP1 突变的频率小于 5%。免疫组化显示 PRKRIP1 位于肿瘤细胞质中。GSEA 显示 PRKRIP1 表达与凋亡相关基因集相关。
PRKRIP1 过表达可能是 CRC 的不良预后生物标志物。虽然已知剪接体因子 PRKRIP1 对剪接至关重要，但我们现在揭示了其表达加速 CRC 进展的方式。
