title: Biomarkers in Tumor Microenvironment? Upregulation of Fibroblast Activation Protein-α Correlates with Gastric Cancer Progression and Poor Prognosis.
abstract: Gastric cancer is the third leading cause of cancer-related mortality worldwide. Recent evidence points to importance of cross talk between cancer cells and the surrounding stroma on gastric cancer progression. Tumor microenvironment biomarkers thus represent a new opportunity for diagnostics innovation. Reactive stromal fibroblasts selectively express the fibroblast activation protein alpha (FAP-α), a homodimeric integral membrane gelatinase that belongs to the serine protease family. We report here that FAP-α expression is significantly elevated in gastric cancer samples by more than fivefold (p < 0.05), using transcriptome data from The Cancer Genome Atlas. Notably, the greatest FAP-α upregulation was observed in the poorly differentiated group (p < 0.001). Moreover, elevated FAP-α expression levels correlated with adverse clinical-pathological characteristics, such as diffuse histological subtype (p < 0.001), advanced pathological stage (p < 0.01) and poor survival. Functional annotation analysis demonstrated that FAP-α upregulation was associated with activation of biological processes implicated in tumor progression, including cell migration and angiogenesis pathways. These observations underscore the possible prognostic significance of FAP-α in gastric cancer and its potential as a novel biomarker for personalized medicine. We caution, however, that further multiomics, biochemical, and animal studies are necessary to ascertain the role of FAP-α as a causative and mechanistic biomarker. Based on pathway analyses, we hypothesize that gastric cancer patients exhibiting FAP-α upregulation might presumably benefit from antiangiogenic drugs in addition to standard therapeutic regimens. We call for future research focusing on the tumor microenvironment biomarkers in clinical oncology.
authors.affiliation: 1 Center of Laboratory Medicine, Danyang Hospital Affiliated to Nantong University , Danyang, 212300, China .
authors.forename: Mengmou
authors.initials: M
authors.lastname: Hu
authors.affiliation: 2 Department of Gastrointestinal Surgery, Wuxi Fourth People's Hospital , Wuxi, China .
authors.forename: Chengjia
authors.initials: C
authors.lastname: Qian
authors.affiliation: 3 Institute of Pharmaceutical Analysis, College of Pharmacy, Jinan University , Guangzhou, China .
authors.forename: Ziwei
authors.initials: Z
authors.lastname: Hu
authors.affiliation: 2 Department of Gastrointestinal Surgery, Wuxi Fourth People's Hospital , Wuxi, China .
authors.forename: Bojian
authors.initials: B
authors.lastname: Fei
authors.affiliation: 3 Institute of Pharmaceutical Analysis, College of Pharmacy, Jinan University , Guangzhou, China .
authors.forename: Haibo
authors.initials: H
authors.lastname: Zhou
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism; D019295:Computational Biology; D057225:Data Mining; D010450:Endopeptidases; D018093:Gelatinases / Q000378:metabolism*; D006801:Humans; D055048:Integrative Medicine; D008565:Membrane Proteins / Q000378:metabolism*; D011379:Prognosis; D012697:Serine Endopeptidases / Q000378:metabolism*; D013274:Stomach Neoplasms / Q000378:metabolism* / Q000473:pathology; D000099167:Fibroblast Activation Protein Alpha
chemical_list: D014408:Biomarkers, Tumor; D010450:Endopeptidases; D018093:Gelatinases; D008565:Membrane Proteins; D012697:Serine Endopeptidases; D000099167:Fibroblast Activation Protein Alpha
keywords: biomarkers; cancer; computational biology; data mining; integrative biology