Transcriptomic profiling on localized gastric cancer identified CPLX1 as a gene promoting malignant phenotype of gastric cancer and a predictor of recurrence after surgery and subsequent chemotherapy

Abstract

Background: Localized gastric cancer (GC) becomes fatal once recurring. We still have room for improving their prognoses.

Methods: Transcriptomic analysis was done on surgically resected specimens of 16 patients with UICC stage III GC who underwent curative gastrectomy and adjuvant oral fluoropyrimidine monotherapy. Four of them were free from disease for longer than 5 years, and the others experienced metachronous metastasis within 2 years after surgery. Quantitative RT-PCR determined mRNA expression levels of primary gastric cancer tissues, which were collected from 180 patients who underwent gastric resection for stage II-III GC without preoperative treatment between 2001 and 2014. We tested alteration of malignant phenotypes including drug resistance of GC cell lines by siRNA and shRNA-mediated knockdown and forced expression experiments.

Results: CPLX1 was identified as a candidate biomarker for GC recurrence among 57,749 genes. Inhibiting and forced expression experiments indicated that CPLX1 promotes proliferation, motility, and invasiveness of GC cells, and decreases apoptosis and sensitivity to fluorouracil. Subcutaneous xenograft mouse models revealed that shRNA-mediated knockdown of CPLX1 also attenuated tumor growth of MKN1 cells in vivo. Overexpression of CPLX1 in gastric cancer tissue correlated with worse prognosis and was an independent risk factor for peritoneal recurrence in subgroups receiving adjuvant chemotherapy.

Conclusions: CPLX1 may represent a biomarker for recurrence of gastric cancer and a target for therapy.

Keywords: CPLX1; Chemotherapy; Gastric cancer; Recurrence; Transcriptome.