High complement protein C1q levels in pulmonary fibrosis and non-small cell lung cancer associated with poor prognosis

Abstract

Background Idiopathic pulmonary fibrosis (IPF) is the most common type of interstitial pneumonia. Lung cancer, mainly non-small cell lung cancer (NSCLC), is a complication of idiopathic pulmonary fibrosis. IPF is also an independent risk factor of lung cancer. Some studies have shown that the complement system can promote the progression of interstitial pulmonary fibrosis. In addition, C1q has also demonstrated to exert a tumor-promoting effect in many tumors. However, the role of C1q in idiopathic pulmonary fibrosis and lung cancer still remain unclear. Methods We selected common differentially expressed genes in IPF and non-small cell lung cancer using datasets from GEO, and investigated common hub gene. The hub genes were validated in IPF by establishing mouse model of IPF and using another four datasets from the GEO. Multiple databases were analyzed including those of Kaplan–Meier Plotter, Tumor Immune Estimation Resource (TIMER2.0) and the Human Protein Atlas (HPA) for NSCLC. Results In this study, 37 common DEGs were identified in IPF and NSCLC including 32 up-regulated genes and 5 down-regulated genes, and C1q was identified as common hub gene. The methylation status of C1q decreased and the expression levels of C1q increased in both lung cancer and idiopathic pulmonary fibrosis. The prognosis of non-small cell lung cancer and IPF patients with high levels of C1q is poor. Conclusions These results show that C1q participates in pulmonary fibrosis and non-small cell lung cancer, and may be a potential diagnostic / prognostic biomarker or a therapeutic target.

C1q+ macrophages: passengers or drivers of cancer progression

“…high C1q) promotes CD8+ T cell dysfunction and tumor progression 20 . In lung cancer and idiopathic pulmonary fibrosis, the methylation status of C1q decreases as compared to healthy tissue, leading to an increase in tumor associated C1Q expression, which is associated with poor prognosis 23 .…”

Inhibition of antiapoptotic BCL-2 proteins with ABT-263 induces fibroblast apoptosis, reversing persistent pulmonary fibrosis

“…We found that C1qb was higher in serum of our fibrotic mice compared with saline-treated mice. C1q has been previously shown to activate pulmonary fibroblasts in a model of murine silicosis ( 69 ), and increased expression in lung tissue has been associated with a poor prognosis in IPF ( 70 ). Finally, we found that cytochrome c , a serum marker of apoptosis ( 33 , 34 ) was higher in ABT-263–treated fibrotic mice.…”

Risk factors and actionable molecular signatures in COVID-19-associated lung adenocarcinoma and lung squamous cell carcinoma patients

“…Moreover, an in vitro study has recently shown that CCNB2 serves as a prognostic indicator and therapeutic target for LUAD patients infected with COVID-19 [ 69 ]. Additionally, other deregulated genes in LC i.e., C1QB have been found to be overexpressed in both NSCLC and IPF patients and reported to act as an unfavorable survival indicator for both diseases [ 70 ]. Furthermore, C1QB expression level has recently been proposed to be able to discriminate the macrophage infiltration levels between healthy subjects and COVID-19 patients [ 71 ].…”