Ding Cheng, Yu Zhangping, Li Xianliang, Zhu Jiqiao, Dai Menghua, He Qiang
Department of Hepatobiliary Surgery, Beijing Chao-Yang Hospital Affiliated to Capital Medical University, Beijing 100020, P.R. China.
Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, P.R. China.
Oncol Lett. 2023 Jan 5;25(2):77. doi: 10.3892/ol.2023.13663. eCollection 2023 Feb.
Pancreatic cancer (PC) is a stubborn malignancy with high lethality and a low 5-year overall survival (OS) rate. Collagen type VII α1 chain (COL7A1), a major component of the extracellular matrix, serves important roles in numerous physiological processes and various illnesses. COL7A1 protein acts as an anchoring fibril between the external epithelial cells and the underlying stroma, and mutation of COL7A1 could cause recessive dystrophic epidermolysis bullosa. Raw data for PC were acquired from The Cancer Genome Atlas and the Gene Expression Omnibus database, and raw data for the normal pancreas were obtained from the Genotype-Tissue Expression database. COL7A1 mRNA expression in PC tissues was compared with that in either paired (GSE15471 dataset) or unpaired (all other data) normal pancreas tissues. The association between COL7A1 mRNA expression and clinicopathological factors was assessed using logistic regression analysis. Cox analysis and Kaplan-Meier analysis were used to evaluate the role of COL7A1 mRNA expression in prognosis and nomograms were constructed. Gene Ontology analysis, Kyoto Encyclopedia of Genes and Genomes analysis, Gene Set Enrichment Analysis (GSEA) and single-sample GSEA (ssGSEA) were performed to evaluate the relevant functions of COL7A1 and correlation with immune cell infiltration. Furthermore, reverse transcription-quantitative PCR was used to assess the mRNA expression levels of COL7A1 in PC. The present study demonstrated that COL7A1 mRNA expression was higher in PC tissues compared with in normal pancreas tissues. The Kaplan-Meier survival analysis indicated that patients with PC with high COL7A1 mRNA expression had shorter overall survival (OS), disease-specific survival (DSS) and progression-free interval (PFI) times compared with patients with PC with low COL7A1 mRNA expression. Multivariate analysis demonstrated that COL7A1 mRNA expression was an independent risk factor for OS, DSS and PFI. Nomogram and calibration plots were constructed to predict the prognosis of patients with PC. GSEA demonstrated that high mRNA expression levels of COL7A1 were associated with multiple cancer-related pathways. ssGSEA analysis indicated that COL7A1 expression was positively associated with natural killer CD56bright cells and T helper (Th)2 cells, and negatively associated with Th17 cells and eosinophils. The results of the present study suggested that COL7A1 could be an independent biomarker and an influential moderator of immune infiltration in PC.
胰腺癌（PC）是一种具有高致死率且5年总生存率（OS）较低的顽固性恶性肿瘤。Ⅶ型胶原蛋白α1链（COL7A1）是细胞外基质的主要成分，在众多生理过程和各种疾病中发挥重要作用。COL7A1蛋白作为外部上皮细胞与下方基质之间的锚定纤维，COL7A1的突变可导致隐性营养不良性大疱性表皮松解症。胰腺癌的原始数据来自癌症基因组图谱和基因表达综合数据库，正常胰腺的原始数据来自基因型-组织表达数据库。将胰腺癌组织中COL7A1 mRNA表达与配对（GSE15471数据集）或未配对（所有其他数据）的正常胰腺组织中的表达进行比较。使用逻辑回归分析评估COL7A1 mRNA表达与临床病理因素之间的关联。采用Cox分析和Kaplan-Meier分析评估COL7A1 mRNA表达在预后中的作用并构建列线图。进行基因本体分析、京都基因与基因组百科全书分析、基因集富集分析（GSEA）和单样本GSEA（ssGSEA）以评估COL7A1的相关功能及其与免疫细胞浸润的相关性。此外，采用逆转录定量PCR评估胰腺癌中COL7A1的mRNA表达水平。本研究表明，与正常胰腺组织相比，胰腺癌组织中COL7A1 mRNA表达更高。Kaplan-Meier生存分析表明，与COL7A1 mRNA表达低的胰腺癌患者相比，COL7A1 mRNA表达高的胰腺癌患者的总生存期（OS）、疾病特异性生存期（DSS）和无进展生存期（PFI）更短。多变量分析表明，COL7A1 mRNA表达是OS、DSS和PFI的独立危险因素。构建列线图和校准图以预测胰腺癌患者的预后。GSEA表明，COL7A1的高mRNA表达水平与多种癌症相关通路有关。ssGSEA分析表明，COL7A1表达与自然杀伤CD56bright细胞和辅助性T（Th）2细胞呈正相关，与Th17细胞和嗜酸性粒细胞呈负相关。本研究结果表明，COL7A1可能是胰腺癌中一种独立的生物标志物和免疫浸润的有影响的调节因子。
