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

Abstract

<b>Background:</b> Collagen type 1 alpha 1 chain (<i>COL1A1</i>) is an extracellular matrix protein comprising two alpha 1 chains and one alpha 2 chain. Our previous study identified that <i>COL1A1</i> is the key gene during the development and progression of lung adenocarcinoma by multi-omics analysis. However, the clinical significance of <i>COL1A1</i> expression in lung cancer samples remains largely unknown. Here, we aimed to evaluate the level of <i>COL1A1</i> in lung cancer samples and correlate its level with the clinical outcome. <b>Methods:</b> <i>COL1A1</i> 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 <i>COL1A1</i>. Immunohistochemistry staining and enzyme-linked immunosorbent assay were used to detect <i>COL1A1</i> expression in tissues and serum, respectively. <b>Results:</b> We identified an elevation of <i>COL1A1</i> in mRNA level and gene amplification in lung cancer tissues compared with normal lung tissues. High <i>COL1A1</i> expression was observed in lung cancer tissues and serum (<i>P</i> < 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 (<i>P</i> < 0.05). High <i>COL1A1</i> expression was associated with poor progression-free survival (PFS) and chemoresistance in lung cancer patients (<i>P</i> < 0.05). Multivariable Cox-regression analysis showed that <i>COL1A1</i> expression was an independent prognostic factor (<i>P</i> < 0.05). Furthermore, the area under the receiver operating characteristic (AUC) curve was 0.909 for the combined <i>COL1A1</i> and carcinoembryonic antigen (CEA) measurement. <b>Conclusion:</b> Our findings revealed that <i>COL1A1</i> 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.