Research Article: Aberrant FAM64A mRNA expression is an independent predictor of poor survival in pancreatic cancer

Date Published: January 29, 2019

Publisher: Public Library of Science

Author(s): Yan Jiao, Zhuo Fu, Yanqing Li, Wei Zhang, Yahui Liu, Aamir Ahmad.

http://doi.org/10.1371/journal.pone.0211291

Abstract

FAM64A, a marker of cell proliferation, has been investigated as a potential biomarker in several cancers. In the present study, we examined the value of FAM64A expression in the diagnosis and prognosis of pancreatic cancer through bioinformatics analysis of data obtained from The Cancer Genome Atlas (TCGA) database. The diagnostic value of FAM64A expression in pancreatic cancer tissue was deteremined through receiver operating characteristic (ROC) curve analysis, and based on the obtained cut-off value, patients were divided into two groups (high FAM64A expression and low FAM64A expression). Chi-square and Fisher exact tests were applied to identify associations between FAM64A expression and clinical features. Moreover, the effect of FAM64A expression in the survival of pancreatic cancer patients was observed by Kaplan-Meier and Cox analyses. Gene set enrichment analysis (GSEA) was performed using the TCGA dataset. Our results showed that high FAM64A expression in pancreatic cancer was associated with survival status, overall survival (OS), and recurrence. The area under the ROC curve was 0.736, which indicated modest diagnostic value. Patients with higher FAM64A expression had significantly shorter OS and recurrence-free survival (RFS) times. Multivariate survival analysis demonstrated that high FAM64A expression was an independent risk factor for OS and RFS. GSEA identified mitotic spindles, myc targets, MTORC1 signaling, G2M checkpoint, E2F targets, DNA repair, glycolysis and unfolded protein response as differentially enriched with the high FAM64A expression phenotype. In conclusion, high FAM64A mRNA expression is an independent risk factor for poor prognosis in pancreatic cancer.

Partial Text

Pancreatic cancer is associated with a high mortality rate worldwide. Although the global incidence is relatively low (about 8/100000 persons per year) [1], the 5-year survival rate is less than 5%. The poor survival rate is, in part, due to late detection of advanced stage disease, and thus, methods for early and accurate diagnosis of pancreatic cancer would help to improve outcomes for these patients. Currently, the diagnosis of pancreatic cancer is mainly based on imaging analyses, including computed tomography (CT) and magnetic resonance imaging (MRI). Unfortunately, even these imaging modalities are ineffective in some cases of pancreatic cancer [2]. Therefore, the identification of a reliable biomarker for pancreatic cancer diagnosis and prognosis has clinical significance.

Our study found that the high FAM64A expression was associated with poor survival status and recurrence in pancreatic cancer. Kaplan-Meier curves for OS and RFS also showed that higher expression of FAM64A was associated with worse outcomes in pancreatic cancer patients. Univariate and multivariate Cox analyses indicated the FAM64A mRNA expression may be a useful biomarker for pancreatic cancer prognosis, and ROC analysis confirmed the diagnostic value of FAM64A expression in pancreatic cancer.

Our data demonstrate that FAM64A is upregulated in pancreatic cancer, and elevated FAM64A expression correlates with clinical progression and serves as an independent risk factor for OS and RFS in pancreatic cancer patients. Our findings suggest that FAM64A may be a useful biomarker in the diagnosis and prognosis of pancreatic cancer.

 

Source:

http://doi.org/10.1371/journal.pone.0211291

 

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