Collagen type 1 alpha 1 chain is a novel predictive biomarker of poor progression-free survival and chemoresistance in metastatic lung cancer.
Collagen type 1 alpha 1 chain is a novel predictive biomarker of poor progression-free survival and chemoresistance in metastatic lung cancer.
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1 型胶原蛋白 α1 链是转移性肺癌无进展生存率和化疗耐药性较差的新型预测生物标志物
DOI：
10.7150/jca.59723
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发表时间：
2021
影响因子：
3.9
通讯作者：
Wang M
中科院分区：
文献类型：
--
作者：
Hou L;Lin T;Wang Y;Liu B;Wang M
1型胶原α 1链（Collagentype1alpha1chain，COL1A1）是一种细胞外基质蛋白，由两条α 1链和一条α 2链组成。我们前期的研究通过多组学分析确定了COL1A1是肺腺癌发生发展的关键基因。然而，肺癌样本中COL1A1表达的临床意义在很大程度上仍然未知。在这里，我们的目的是评估肺癌样本中COL1A1的水平，并将其水平与临床结果相关联。方法：使用Oncomine数据库（www.oncomine.org）分析肺癌样本中的COL1A1基因表达。共308例肺癌样本（208例福尔马林固定石蜡包埋组织和100例血液样本）进行了COL1A1蛋白表达评估。采用免疫组织化学染色法和酶联免疫吸附法分别检测组织和血清中COL1A1的表达。结果：肺癌组织中COL1A1的mRNA水平和基因扩增均高于正常肺组织。COL1A1在肺癌组织和血清中均呈高表达（P < 0.05），其表达与周围型肺癌、肿瘤直径较大、有无淋巴结转移和远处转移、TNM分期高、吸烟有关（P < 0.05）。COL1A1高表达与肺癌患者的无进展生存期（PFS）和化疗耐药相关（P < 0.05）。多变量Cox回归分析显示COL1A1表达是独立的预后因素（P < 0.05）。此外，COL1A1和癌胚抗原（CEA）联合测定的受试者工作特征（AUC）曲线下面积为0.909。结论：我们的研究结果表明，COL1A1可以作为一种新的诊断，预后和化疗耐药的人肺癌的生物标志物，这些结果提供了一个潜在的治疗策略，肺癌患者。
Background: Collagen type 1 alpha 1 chain (COL1A1) is an extracellular matrix protein comprising two alpha 1 chains and one alpha 2 chain. Our previous study identified that COL1A1 is the key gene during the development and progression of lung adenocarcinoma by multi-omics analysis. However, the clinical significance of COL1A1 expression in lung cancer samples remains largely unknown. Here, we aimed to evaluate the level of COL1A1 in lung cancer samples and correlate its level with the clinical outcome. Methods:COL1A1 gene expression in lung cancer samples was analyzed using the Oncomine database (www.oncomine.org). A total of 308 lung cancer samples (208 formalin-fixed paraffin-embedded tissues and 100 blood samples) were assessed for protein expression of COL1A1. Immunohistochemistry staining and enzyme-linked immunosorbent assay were used to detect COL1A1 expression in tissues and serum, respectively. Results: We identified an elevation of COL1A1 in mRNA level and gene amplification in lung cancer tissues compared with normal lung tissues. High COL1A1 expression was observed in lung cancer tissues and serum (P < 0.05), it was significantly correlated with the peripheral type tumor, the larger diameter of the tumor, the occurrence of lymph node metastases and distant metastases, a higher TNM stage, and smoking (P < 0.05). High COL1A1 expression was associated with poor progression-free survival (PFS) and chemoresistance in lung cancer patients (P < 0.05). Multivariable Cox-regression analysis showed that COL1A1 expression was an independent prognostic factor (P < 0.05). Furthermore, the area under the receiver operating characteristic (AUC) curve was 0.909 for the combined COL1A1 and carcinoembryonic antigen (CEA) measurement. Conclusion: Our findings revealed that COL1A1 could be used as a novel diagnostic, prognostic, and chemoresistance biomarker of human lung cancer, and these results provide a potential therapeutic strategy for lung cancer patients.
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