Dong Siyuan, Zhu Peiyao, Zhang Shuguang
Department of Thoracic Surgery, The first hospital of China Medical University, Shenyang, Liaoning, China.
PeerJ. 2020 Sep 29;8:e10089. doi: 10.7717/peerj.10089. eCollection 2020.
Squamous cell carcinomas of the lung are an extremely common and deadly form of non-small cell lung cancers. Clinical management of the disease is dependent on staging and metastatic status. Metastasis to the lymph node is especially crucial to diagnose as it occurs at an earlier stage. However, lymphadenectomies are invasive and tumor cells may be overlooked during evaluation.There are limited approved biomarkers for predicting lymph node metastasis with squamous cell carcinomas of the lung (LSCC).
Genome data of 60 tumor-adjacent samples were downloaded from Genome Expression Omnibus. We identified over-expressed HUB genes using Cytoscape as key prognostic markers. The selected markers were further evaluated based on gene ontology and overall expression levels compared to normal tissue using The Cancer Genome Atlas. We further validated these results using clinical biopsy tissue taken from squamous cell carcinoma patients.
Analysis of the genome expression data resulted in 13 relevant hub genes that were differentially expressed in cancerous samples. All of these genes are associated with collagen biosynthesis within the tumor microenvironment. We chose Collagen Type 1 Alpha 1 (COL1A1) as the most relevant prognostic marker due to its high number of pathway connections and over expression in the tumor microenvironment compared to the other 12 genes. Additionally, based on analysis of The Cancer Genome Atlas, tumors with higher levels of COL1A1 expression are associated with poorer overall survival. Finally, evaluation of clinical biopsy samples suggests that overexpression of COL1A1 in the LSCC microenvironment highly correlates with lymph node metastasis. These results suggest COL1A1 is a clinically relevant marker that should be used to justify lymphadenectomies.
肺鳞状细胞癌是一种极其常见且致命的非小细胞肺癌形式。该疾病的临床管理取决于分期和转移状态。淋巴结转移的诊断尤为关键，因为其发生在较早阶段。然而，淋巴结切除术具有侵入性，并且在评估过程中肿瘤细胞可能被忽视。目前用于预测肺鳞状细胞癌（LSCC）淋巴结转移的获批生物标志物有限。
从基因表达综合数据库下载了60个肿瘤邻近样本的基因组数据。我们使用Cytoscape软件识别过表达的关键预后标记基因。根据基因本体论以及与正常组织相比的整体表达水平，对所选标记物进行进一步评估，数据来源于癌症基因组图谱。我们使用取自鳞状细胞癌患者的临床活检组织进一步验证了这些结果。
对基因组表达数据的分析产生了13个在癌组织样本中差异表达的相关关键基因。所有这些基因都与肿瘤微环境中的胶原蛋白生物合成相关。由于与其他12个基因相比，其在肿瘤微环境中的通路连接数量多且过表达，我们选择I型胶原蛋白α1（COL1A1）作为最相关的预后标记物。此外，基于癌症基因组图谱的分析，COL1A1表达水平较高的肿瘤与较差的总生存率相关。最后，对临床活检样本的评估表明，LSCC微环境中COL1A1的过表达与淋巴结转移高度相关。这些结果表明COL1A1是一种临床相关标记物，应用于支持淋巴结切除术的合理性。
