New prognostic markers revealed by RNA-Seq transcriptome analysis after MYC silencing in a metastatic gastric cancer cell line
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Luana de O. Lopes1,*, Jersey H. Maués2,*, Hygor Ferreira-Fernandes1, France K. Yoshioka1, Severino C. Sousa Júnior3, Alcemir R. Santos4, Helem F. Ribeiro5, Juan A. Rey6, Paulo C. Soares2, Rommel R. Burbano2,5 and Giovanny R. Pinto1
1 Genetics and Molecular Biology Laboratory, Federal University of Piauí, Parnaíba, Brazil
2 Laboratory of Molecular Biology, Ophir Loyola Hospital, Belém, Brazil
3 Course of Medicine, Federal University of Piauí, Parnaíba, Brazil
4 Computer Science Department, State University of Piauí, Piripiri, Brazil
5 Institute of Biological Sciences, Federal University of Pará, Belém, Brazil
6 Molecular Oncogenetics Laboratory, Hospital Universitario La Paz, Madrid, Spain
* These authors contributed equally to this work
|Giovanny R. Pinto,||email:||firstname.lastname@example.org|
Keywords: stomach neoplasms; MYC oncogene; transcriptome; gene expression profiling; prognosis
Received: May 13, 2019 Accepted: August 27, 2019 Published: October 08, 2019
MYC overexpression is considered a driver event in gastric cancer (GC), and is frequently correlated with poor prognosis and metastasis. In this study, we evaluated the prognostic value of genes upregulated by MYC in patients with GC. Metastatic GC cells (AGP01) characterized by MYC amplification, were transfected with siRNAs targeting MYC. RNA-seq was performed in silenced and non-silenced AGP01 cells. Among the differentially expressed genes, CIAPIN1, MTA2, and UXT were validated using qRT-PCR, western blot, and immunohistochemistry in gastric tissues of 213 patients with GC; and their expressions were correlated with clinicopathological and survival data. High mRNA and protein levels of CIAPIN1, MTA2, and UXT were strongly associated with advanced GC stages (P < 0.0001). However, only CIAPIN1 and UXT gene expressions were able to predict distant metastases in patients with early-stage GC (P < 0.0001), with high sensitivity (> 92%) and specificity (> 90%). Overall survival rate of patients with overexpressed CIAPIN1 or UXT was significantly lower (P < 0.0001). In conclusion, CIAPIN1 and UXT may serve as potential molecular markers for GC prognosis.
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