The prognostic significance of fibroblast activation protein-α in human lung adenocarcinoma

Abstract

Background: Fibroblast activation protein (FAP) is a type II cell surface-bound integral serine protease, which is an important biomarker of cancer-associated fibroblasts. FAP-α performs several biological activities, including remolding extracellular matrix and acting as an immunosuppressor in the tumor microenvironment. However, the proliferation role of FAP-α in human lung adenocarcinoma has not been fully elucidated. Methods:The expression of FAP-α in 94-paired human lung adenocarcinoma tissues was identified by immunohistochemistry test. The effect of FAP on cell proliferation was examined by CCK-8 assay. RNAsequencing and bioinformatics analysis were utilized to investigate the underlying mechanism. Western blot analysis, quantitative polymerase chain reaction (qPCR), and nude mice experiments, were also conducted for further validation.Results: The proliferation rates of human fibroblast strains FAP-HFF and FAP-BJ, and human lung adenocarcinoma cell line FAP-SPC-A-1 were higher than those of controls. The nude mice experiment also showed that FAP could promote the proliferation of SPC-A-1 cell line in vivo. qPCR and Western blot analysis indicated that CCNB1 was upregulated by the overexpression of FAP in the lung adenocarcinoma cell line. The expression of FAP-α was higher in both the cytoplasm and stroma of lung adenocarcinoma than in adjacent normal tissues. Survival analysis indicated that patients with higher expression of FAP-α in tumor stroma had a poor prognosis (P=0.019). The Cancer Genome Atlas Program (TCGA) data also showed that the expression of FAP within tumor tissues was higher (in both cytoplasm and stroma) compared with that in normal tissues (P<0.05).Conclusions: Our study indicates that FAP-α could facilitate the proliferation of lung adenocarcinoma cells and can be a prognostic marker in human lung adenocarcinoma.

Identification of a Novel Tumor Microenvironment–Associated Eight-Gene Signature for Prognosis Prediction in Lung Adenocarcinoma

“…More and more studies have shown that the occurrence and development of tumors are the results of the dynamic interaction between tumor cells and various components (including immune cells and stromal cells) within the tumor microenvironment (Hui and Chen, 2015;Verrecchia and Redini, 2018;Shi et al, 2020). Therefore, the tumor microenvironment may become a promising target for cancer treatment (Alsaab et al, 2017).…”

Colorectal cancer cell intrinsic fibroblast activation protein alpha binds to Enolase1 and activates NF-κB pathway to promote metastasis

“…Larrinaga and colleagues 46 have reported that FAP expression in cancer tissues is associated with CRC lymph node metastasis and liver metastasis. In other types of tumors, high levels of FAP in tumors are associated with poor survival 47 – 49 , and in lung cancer, ENO1 is a biomarker associated with patient survival 50 . Our data show FAP and ENO1 could be a potential biomarker of CRC patients.…”

Advances in CAR-T Cell Genetic Engineering Strategies to Overcome Hurdles in Solid Tumors Treatment

“…Among them, FAP has recently emerged as the most promising target ( 149 ). FAP is a cell surface serine protease that is highly expressed on the CASCs of various human cancer types ( 150 ), such as lung ( 151 ), prostate ( 152 ), pancreatic ( 153 ), colorectal ( 154 ), and ovarian cancer ( 155 ). In contrast, the expression of this proteolytic enzyme on normal quiescent adult stromal cells and benign tumors is reported to be low to undetectable.…”