Expression of collagen type 1 alpha 1 indicates lymph node metastasis and poor outcomes in squamous cell carcinomas of the lung.

Expression of collagen type 1 alpha 1 indicates lymph node metastasis and poor outcomes in squamous cell carcinomas of the lung.
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1 型α1 胶原蛋白的表达表明淋巴结转移和肺鳞状细胞癌的不良预后。

DOI:
10.7717/peerj.10089
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发表时间:
2020
期刊:
影响因子:
2.7
通讯作者:
Zhang S
Zhang S
中科院分区:
生物学3区
文献类型:
--
作者:
Dong S;Zhu P;Zhang S

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肺鳞状细胞癌是一种非常常见和致命的非小细胞肺癌。该疾病的临床治疗取决于分期和转移状态。转移到淋巴结的诊断尤其重要,因为它发生在早期阶段。然而,淋巴结切除术是侵入性的,在评估过程中可能会忽略肿瘤细胞。用于预测肺鳞状细胞癌(LSCC)淋巴结转移的生物标志物有限。从Genome Expression Omnibus下载60例肿瘤邻近样本的基因组数据。我们使用Cytoscape作为关键的预后标记物来鉴定过表达的HUB基因。选择的标记进一步评估基于基因本体和总体表达水平,与正常组织相比,使用癌症基因组图谱。我们进一步用取自鳞状细胞癌患者的临床活检组织验证了这些结果。基因组表达数据分析得出13个相关枢纽基因在癌样中差异表达。所有这些基因都与肿瘤微环境中的胶原蛋白生物合成有关。我们选择胶原型1 α 1 (COL1A1)作为最相关的预后标志物,因为与其他12个基因相比,它在肿瘤微环境中具有大量的通路连接和过表达。此外,根据对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期相关。最后,临床活检样本的评估表明,COL1A1在LSCC微环境中的过度表达与淋巴结转移高度相关。这些结果表明COL1A1是一个临床相关的标志物,应该用来证明淋巴结切除术的有效性。
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.
DOI: 10.18632/oncotarget.10949
发表时间: 2017-08-08
期刊: Oncotarget
影响因子: --
作者:
Cao B;Feng L;Lu D;Liu Y;Liu Y;Guo S;Han N;Liu X;Mao Y;He J;Cheng S;Gao Y;Zhang K
通讯作者: Zhang K