Abstract
Lung adenocarcinoma (LUAD) is one of the major types of lung cancer. Tumor-infiltrating immune cells (TIICs) are positively associated with overall survival (OS) in LUAD. The SPARC/osteonectin, cwcv and kazal-like domains proteoglycan 2 (SPOCK2) is a complex type of secreted proteoglycan involved in forming a protective barrier against viral infection. The purpose of this study was to investigate the relationship between SPOCK2 and TIICs and the prognostic role of SPOCK2 in LUAD. The GEPIA2, GEO, CPTAC, and HPA databases were analyzed to examine both the mRNA and protein expression of SPOCK2 in LUAD. GEPIA2 and the Kaplan-Meier Plotter (KM Plotter) were used to evaluate the prognostic value of SPOCK2 in LUAD patients. TCGA data were examined for a correlation between SPOCK2 expression and clinical characteristics. Gene enrichment analyses were performed to explore the underlying mechanism of SPOCK2 based on LinkedOmics. RegNetwork was used to predict the regulators of SPOCK2. The correlation between SPOCK2 and TIICs, including immune infiltration level and relative proportion was investigated via TIMER. KM Plotter was also used to evaluate the prognostic role of SPOCK2 expression in LUAD with enriched and decreased TIIC subgroups. We found SPOCK2 was significantly downregulated in LUAD compared with that in non-tumor controls and was correlated with clinical parameters. Moreover, a high SPOCK2 expression level predicted better survival. The SPOCK2-associated regulatory network was constructed. SPOCK2 influenced the TIIC infiltration level and relative proportion in LUAD. Furthermore, a high SPOCK2 expression level was associated with a favorable prognosis in enriched CD4 + T cells and macrophage subgroups in LUAD. In conclusion, a high level of SPOCK2 expression predicted favorable prognosis and was significantly correlated with TIICs in LUAD. Therefore, the expression of SPOCK2 may affect the prognosis of LUAD partly due to TIICs.
Highlights
Lung cancer has become the most common cancer type and causes the largest number of cancer-related deaths in the world (Siegel et al, 2019)
The results revealed that the SPOCK2 mRNA expression level was lower in Lung adenocarcinoma (LUAD) than in non-tumor lung tissue (P < 0.05, Figure 1A)
IHC staining data from Human Pathology Atlas Project (HPA) database indicated that medium levels of SPOCK2 expression were present in normal lung tissues, while low levels of expression were observed in LUAD tissues (Figure 1D)
Summary
Lung cancer has become the most common cancer type and causes the largest number of cancer-related deaths in the world (Siegel et al, 2019). Lung adenocarcinoma (LUAD) is a crucial histological phenotype of lung cancer (Testa et al, 2018). The effect of immunotherapy on LUAD progression and outcome depends on both the cancer phenotype and tumor-infiltrating immune cell (TIIC) subsets in the tumor microenvironment. It was reported that TIICs are positively associated with better survival in LUAD, which highlights the importance of TIICs in the clinical outcomes of LUAD patients (Vafadar, 2019). It was reported that SPOCK2 can prevent viral infection in lung epithelial cells (Ahn et al, 2019). Its association with prognosis in LUAD and its possible immune mechanisms are still elusive. We aimed to examine these immune mechanisms and the prognostic role of SPOCK2 in LUAD
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
