Gene expression analysis of head and neck squamous cell carcinoma (HNSCC) cell lines.

Human cancer cell lines are the most frequently used preclinical models in the study of cancer biology and the development of therapeutics. Although anatomically diverse, human papillomavirus (HPV)-driven cancers have a common etiology and similar mutations that overlap with but are distinct from those found in HPV-negative cancers. Building on prior studies that have characterized subsets of head and neck squamous cell carcinoma (HNSCC) and cervical squamous cell carcinoma (CESC) cell lines separately, we performed genomic, viral gene expression, and viral integration analyses on 74 cell lines that include all readily-available HPV-positive (9 HNSCC, 8 CESC) and CESC (8 HPV-positive, 2 HPV-negative) cell lines and 55 HPV-negative HNSCC cell lines. We used over 700 human tumors for comparison. Mutation patterns in the cell lines were similar to those of human tumors. We confirmed HPV viral protein and mRNA expression in the HPV-positive cell lines. We found HPV types in three CESC cell lines that are distinct from those previously reported. We found that cell lines and tumors had similar patterns of viral gene expression; there were few sites of recurrent HPV integration. As seen in tumors, HPV integration did appear to alter host gene expression in cell lines. The HPV-positive cell lines had higher levels of p16 and lower levels of Rb protein expression than did the HPV-negative lines. Although the number of HPV-positive cell lines is limited, our results suggest that these cell lines represent suitable models for studying HNSCC and CESC, both of which are common and lethal. RNAseq from individual cell lines grown under standard tissue culture conditions. ***Pleaes note that the raw sequence data cannot be provided due to these being old cell lines without proper consents. Please contact the submitter for the sequence data***人类癌细胞系是癌症生物学研究与治疗药物开发中应用最广泛的临床前模型。尽管解剖学特征存在异质性，人乳头瘤病毒（Human papillomavirus, HPV）驱动型癌症具有共同的病因学基础，且存在与HPV阴性癌症重叠但又独具特征的相似突变谱。本研究在既往分别对头颈部鳞状细胞癌（head and neck squamous cell carcinoma, HNSCC）与宫颈鳞状细胞癌（cervical squamous cell carcinoma, CESC）细胞系亚群开展特征分析的研究基础上，对74株细胞系进行了基因组学、病毒基因表达及病毒整合分析。该74株细胞系涵盖所有可获取的HPV阳性细胞系（9株HNSCC、8株CESC）、CESC细胞系（其中8株HPV阳性、2株HPV阴性）以及55株HPV阴性HNSCC细胞系。研究纳入700余例人类肿瘤样本作为对照，结果显示细胞系的突变谱与人类肿瘤样本高度相似。本研究验证了HPV阳性细胞系中的HPV病毒蛋白及mRNA表达情况，在3株CESC细胞系中检测到了此前未见报道的HPV型别。我们发现细胞系与肿瘤的病毒基因表达谱高度相似，且复发性HPV整合位点极少。与肿瘤中的表现一致，HPV整合确实会改变细胞系的宿主基因表达模式。相较于HPV阴性细胞系，HPV阳性细胞系的p16表达水平更高，而Rb蛋白表达水平更低。尽管HPV阳性细胞系的数量有限，但本研究结果表明，此类细胞系可作为研究HNSCC与CESC的适宜模型——这两类癌症均为高发且致死性极强的肿瘤。本数据集包含在标准组织培养条件下培养的单株细胞系的RNA测序（RNA sequencing, RNAseq）数据。请注意：由于本研究涉及的老旧细胞系未获得合规的知情同意，无法提供原始测序数据。若需获取测序数据，请与数据提交者联系。