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Abstract
Prognostic significance of family with sequence similarity 83, member D (FAM83D) in hepatocellular carcinoma (HCC) patients has not been well-investigated using Gene Expression Omnibus (GEO) series and TCGA database, we compared FAM83D expression levels between tumor and adjacent tissues, and correlated FAM83D in tumors with outcomes and clinico-pathological features in HCC patients. Validated in GSE33006, GSE45436, GSE84402 and TCGA, FAM83D was significantly overexpressed in tumor tissues than that in adjacent tissues (all P<0.01). FAM83D up-regulation was significantly associated with worse overall survival (OS) and disease-free survival (DFS) in HCC patients (Log rank P=0.00583 and P=4.178E-04, respectively). Cox analysis revealed that FAM83D high expression was significantly associated with OS in HCC patients [hazard ratio (HR) = 1.44, 95% confidence interval (CI) = 1.005–2.063, P=0.047]. Additionally, patients deceased or recurred/progressed had significantly higher FAM83D mRNA levels than those living or disease-free (P=0.0011 and P=0.0238, respectively). FAM83D high expression group had significantly more male patients and advanced American Joint Committee on Cancer (AJCC) stage cases (P=0.048 and P=0.047, respectively). FAM83D mRNA were significantly overexpressed in male (P=0.0193). Compared with patients with AJCC stage I, those with AJCC stage II and stage III–IV had significantly higher FAM83D mRNA levels (P = 0.0346 and P=0.0045, respectively). In conclusion, overexpressed in tumors, FAM83D is associated with gender, AJCC stage, tumor recurrence and survival in HCC.
Highlights
Primary liver cancer, comprising 75–85% cases of hepatocellular carcinoma (HCC), is predicted to be the sixth most commonly diagnosed cancer and the fourth leading cause of cancer death worldwide in 2018 worldwide [1,2,3]
AffyPLM and Limma packages in R program were used for quality assessment and identifying FAM83D mRNA expression levels of tumor and adjacent normal samples in each Gene Expression Omnibus (GEO) profile. edgeR package was used for identifying FAM83D expression levels in tumor and adjacent tissues in HCC patients
As key intermediates in oncogenic EGFR, Mitogen activated kinase-like protein (MAPK), RAS/RAF/MAP kinse-ERK kinase (MEK)/ERK and PI3K/AKT/mTOR signaling, family with sequence similarity 83 (FAM83) involved in a variety of important cancer cell signaling functions and overexpressed in many human cancers [9,10,21,22,23,24]
Summary
Primary liver cancer, comprising 75–85% cases of hepatocellular carcinoma (HCC), is predicted to be the sixth most commonly diagnosed cancer and the fourth leading cause of cancer death worldwide in 2018 worldwide [1,2,3]. Advanced in surgical and nonsurgical therapeutics have been improved over the past decades for the disease, the clinical outcome of HCC remains poor [4] and more than 70% cases developed tumor recurrence at 5 years [5,6]. A higher expression level of a signature of FAM83 family members was associated with poor prognosis in a number of human cancers [10,11]. Emerging evidence indicated that FAM83D expression is elevated in a wide variety of tumor types including ovarian cancer [13], metastatic lung adenocarcinomas [14] and HCC [15,16], suggesting the possibility
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