Diagnostic value of GDF10 for the tumorigenesis and progression in lung squamous cell carcinoma

Abstract

Abstract Background Lung squamous cell carcinoma (LUSC) remains a poor survival rate, calling for a novel molecular with diagnostic and treatment value. Accumulative evidence found bone morphogenetic proteins (BMPs) and their receptors (BMPRs) play important roles in tumorigenesis and progression, however, was lack of comprehensive analysis of their expression in LUSC. Methods . R/Limma package was performed to analyze the differential expression of BMPs/BMPRs in combination of TCGA and GTEx, and explore their expression characteristics with LUSC tumorigenesis in GSE33479. Meanwhile, survminer packages were performed to explore their prognostic value and correlation of clinical features in LUSC. Then, the potential diagnostic biomarkers and mechanisms associated with LUSC progression were further explored through weight gene correlation network analysis (WGCNA). At the same time, LASSO analysis was performed to construct a prognostic risk model for LUSC with the differential expression of BMPs/BMPRs as the core. Finally, the specimens were collected from 33 patients with LUSC and detected by IHC to confirm the relationship between protein levels of the above diagnostic BMPs/BMPRs and progression of LUSC. Results On the whole, 2 upregulated genes (BMP8A, BMP7) and 8 downregulated genes (BMP2, BMP5, BMP6, GDF5, GDF7, GDF10, ACVRL1 and BMPR2) were identified differentially expressed genes in LUSC. In these differentially expressed genes, GDF10 was only a significant correlation with pathological T stage of LUSC (p < 0.001). The co-expressed network showed that the positively related magenta module (Coefficient:0.93, p = 1.4e-70 < 0.001) and the negatively correlated turquoise module (Coefficient:0.89, p = 1e-200) are significantly associated with GDF10. Meanwhile, combining 72 significantly down-regulated genes in magenta module and 351 significantly up-regulated genes in turquoise module together, a prognostic risk model was constructed with GDF10 as the core gene and 5 hub genes (HRASLS, HIST1H2BH, FLRT3, CHEK2 and ALPL) (HR:1.73, 95%CI:1.32–2.28, p = 1e-04 < 0.001). At last, immunohistochemical results verified that the protein expression level of GDF10 decreased with the tumorigenesis and progression of LUSC. Conclusion Both mRNA and protein expression levels of GDF10 acted as an independent protective factor in the tumorigenesis and progression of lung squamous cell carcinoma. As a result, it may be a potential diagnostic biomarker and a new therapeutic target for LUSC.