Overexpression of FIBCD1 Is Predictive of Poor Prognosis in Gastric Cancer

Chunyi Jiang, MA; Jinhong Zhu, MD; Pengcheng Zhou, MA; Huijun Zhu; Wei Wang, MA; Qin Jin, MA; Peng Li, MD

Disclosures

Am J Clin Pathol. 2018;149(6):474-48. 

In This Article

Discussion

FIBCD1 has not been well investigated, and little is known about its characteristics and biological functions. Our study revealed that high FIBCD1 expression correlated with poor prognosis in patients with gastric cancer. FIBCD1 is expressed in a large proportion of the gastrointestinal tract. The active form of FIBCD1 is a 55-kDa homotetramer assembled by disulfide linkages. FIBCD1 is a pattern recognition receptor. The ectodomain of FIBCD1 consists of a polycationic region, a coiled-coil region, and a C-terminal fibrinogen-like recognition domain.[16] The mechanism of FIBCD1 action is speculated to be through endocytosis of bound ligands or signaling.[17,18]

FIBCD1 is a calcium-dependent, high-affinity acetyl group-binding receptor that binds acetylated components, including chitin, which has been shown to have great relevance to the occurrence and development of allergies.[19] Chitin is a natural polymer composed of β-(1-4)–linked N-acetyl glucosamine and the second most abundant biopolymer after cellulose worldwide.[20] Chitin is sensed primarily in the lungs or gut, where it activates a variety of innate (eosinophils, macrophages) and adaptive (interleukin 4/interleukin 13–expressing T helper type 2 lymphocytes) immune cells.[21] Vertebrates are exposed to chitins when they are infected with fungi or nematodes or ingest certain foods.[22] Chitin is typically associated with allergic and parasitic worm immune responses.[23,24] By controlling exposure of the intestine to chitin, FIBCD1 plays an important role in immune response modulation and the immune defense against fungi and parasites.[25–27] FIBCD1 is also located in the epithelium membrane of the small intestine, suggesting a relationship between FIBCD1 and the development of inflammatory bowel diseases.[28] In addition, FIBCD1 is also expected to be a signaling protein because of the presence of two potential phosphorylation sites in its cytoplasmic region;[11] however, the signaling pathway of FIBCD1 is currently unclear.

In this study, we examined the expression of FIBCD1 mRNA and protein in gastric cancer and normal tissues. qRT-PCR analysis demonstrated that mRNA expression of FIBCD1 in gastric cancer tissues was higher than that in normal tissues. IHC analysis further confirmed increased expression of FIBCD1 protein in gastric cancer tissues compared with normal tissues. Moreover, we demonstrated that overexpression of FIBCD1 correlates with age, TNM stage, serum CEA level, and HER-2 level. Finally, we found that FIBCD1 was an independent predictor for the prognosis of gastric cancer in our study population.

Our results indicated that FIBCD1 expression in gastric cancer might be different between age groups; in particular, overexpression of FIBCD1 was more common in older patients. It is generally known that TNM tumor stage is the most important prognostic factor for patients with gastric cancer.[29] Our study shows that positive FIBCD1 staining is significantly related to TNM stage. Increased FIBCD1 expression was related to tumor invasion depth and metastatic processes of gastric cancer and also significantly correlated with poor survival outcomes. HER-2 is an important biomarker for therapeutic assessment of gastric with HER-2 protein overexpression.[30] Our results show that FIBCD1 expression in gastric cancer has a correlation with HER-2. The KM plotter further validated that high FIBCD1 expression conferred reduced survival in patients with gastric cancer. Besides high FIBCD1 expression, high CEA expression might also contribute to the diagnosis of gastric cancer and is a potential prognostic indicator. To our knowledge, this is the report that shows that FIBCD1 may hold great promise in predicting clinical outcomes of patients with gastric cancer.

Despite some merits, our study has some limitations. First, since this is a retrospective study, the sample size and quality of samples are limited. Second, the underlying mechanisms by which FIBCD1 affects the development and progression of gastric cancer have not been studied. Mechanistic studies should be performed to provide biological evidence of the role of FIBCD1 in gastric carcinogenesis. Third, immunohistochemical methods might not be able to precisely determine FIBCD1 expression in gastric cancer cells.

Biomarkers play an important role in early diagnosis, disease prevention, identification of drug targets, and other drug reactions.[31] Many patients with cancer are diagnosed at a late stage and have lost the chance for curative surgery. As a result, it is very likely that the cancer will recur due to the limited efficacy of systemic therapies for metastatic disease. For decades, biomedical scientists have been developing new methods to diagnose cancer at an early and curable stage as well as optimal treatments for individual patients. Improvement in early diagnosis will greatly increase the likelihood of benefits in clinical outcomes. Identifying biomarkers in the early stages of disease is important to determine the type and stage of disease and predict the results of different treatment options and the pharmacological response.[32] Thus, identifying effective biomarkers is very important for the development of new cancer management and treatment strategies.

In conclusion, our study demonstrates that the expression of FIBCD1 is significantly increased in gastric cancer tissues compared with normal tissues, and FIBCD1 overexpression is related to poor prognosis. FIBCD1 may be a novel prognostic marker in gastric cancer; however, the mechanisms of FIBCD1 function require further study in the future.

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