■头颈部鳞状细胞癌(HNSCC)是由不同的外源性危险因素引起的,包括吸烟,酒精消费,和HPV感染。碱基切除修复(BER)是修复氧化性DNA损伤的前线,它由DNAN-糖基化酶蛋白(OGG1)和其他BER因子(包括DNA聚合酶β(POLB))启动。
■探索HNSCC中的BER基因(OGG1,POLB)过表达是否会改变基因组完整性,免疫原性,及其在预后价值中的作用。
■RNA测序(RNA-Seq)和临床信息(年龄,性别,组织学分级,生存状态,和阶段)从癌症基因组图谱中检索到530例HNSCC患者。将患者数据分类为HPV阳性或阴性,以分析包括肿瘤分期在内的肿瘤数据,POLB,和OGG1基因表达。
■检索的HNSCC数据的RNA-Seq,并使用非配对t检验比较突变计数和非整倍性评分。TIMER算法用于计算6种浸润免疫细胞(CD4+T细胞,CD8+T细胞,B细胞,中性粒细胞,巨噬细胞,和树突状细胞)基于RNA-Seq表达谱数据。POLB之间的相关性,使用TIMER2.0通过Spearman相关性分析计算OGG1和免疫细胞。
■我们的数据分析表明,BER基因在HNSCC肿瘤中经常过表达并增加突变计数。此外,OGG1和POLB过表达与免疫细胞的低浸润有关,低免疫检查点基因表达(PD-1,细胞毒性T淋巴细胞抗原4,程序死亡配体1和程序死亡配体2),和先天免疫信号基因。此外,在人乳头瘤病毒(HPV)阳性肿瘤中,BER因子失调有较好的总生存期.
■我们的分析表明,BER基因组的失调可能是HNSCC癌症中潜在的预后标志物和/或免疫检查点阻断的有吸引力的靶标。然而,我们的观察仍需要进一步的基于实验的科学验证研究.
UNASSIGNED: Head and neck squamous carcinoma (HNSCC) is caused by different exogenous risk factors including smoking cigarettes, alcohol consumption, and HPV infection. Base excision repair (BER) is the frontline to repair oxidative DNA damage, which is initiated by the DNA N-glycosylase proteins (OGG1) and other BER factors including DNA polymerase β (POLB).
UNASSIGNED: Explore whether BER genes\' (OGG1, POLB) overexpression in HNSCC alters genomic integrity, immunogenicity, and its role in prognostic value.
UNASSIGNED: RNA sequencing (RNA-Seq) and clinical information (age, gender, histological grade, survival status, and stage) of 530 patients of HNSCC were retrieved from the Cancer Genome Atlas. Patients\' data are categorized HPV positive or negative to analyze the tumor data including the tumor stage, POLB, and OGG1 gene expression.
UNASSIGNED: RNA-Seq of HNSCC data retrieved and mutation count and aneuploidy score were compared using an unpaired t-test. The TIMER algorithm was used to calculate the tumor abundance of six infiltrating immune cells (CD4+ T cells, CD8+ T cells, B cells, neutrophils, macrophages, and dendritic cells) based on RNA-Seq expression profile data. The correlation between the POLB, OGG1, and immune cells was calculated by Spearman correlation analysis using TIMER 2.0.
UNASSIGNED: Our data analysis reveals that BER genes frequently overexpressed in HNSCC tumors and increase mutation count. In addition, OGG1 and POLB overexpression are associated with low infiltration of immune cells, low immune checkpoint gene expression (PD-1, cytotoxic T-lymphocyte antigen 4, program death ligand 1, and program death ligand 2), and innate immune signaling genes. Furthermore, dysregulated BER factors in Human papillomavirus (HPV) positive tumors had better overall survival.
UNASSIGNED: Our analysis suggests that dysregulation of the BER genes panel might be a potential prognosis marker and/or an attractive target for an immune checkpoint blockade in HNSCC cancers. However, our observation still requires further experimental-based scientific validation studies.