Collagen type 1 alpha 1 chain is a novel predictive biomarker of poor progression-free survival and chemoresistance in metastatic lung cancer

型胶原蛋白 α 1 链是转移性肺癌中不良无进展生存期和化疗耐药性的新型预测生物标志物

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作者:Lingjie Hou, Tie Lin, Yicun Wang, Bao Liu, Meng Wang

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.

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.

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.

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