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FAM46C Serves as a Predictor of Hepatic Recurrence in Patients with Resectable Gastric Cancer

Haruyoshi Tanaka MD, Mitsuro Kanda MD, PhD, FACS, Dai Shimizu MD, PhD, Chie Tanaka MD, PhD, Daisuke Kobayashi MD, PhD, Masamichi Hayashi MD, PhD, Naoki Iwata MD, PhD, Suguru Yamada MD, PhD, FACS, Tsutomu Fujii MD, PhD, FACS, Goro Nakayama MD, PhD, Hiroyuki Sugimoto MD, PhD, Michitaka Fujiwara MD, PhD, Yukiko Niwa MD, PhD, Yasuhiro Kodera MD, PhD, FACS
Translational Research and Biomarkers
Volume 24, Issue 11 / October , 2017

ABSTRACT

Background

Gastric cancer (GC) relapse can occur even if curative resection is achieved. Biomarkers predicting recurrence are needed to provide appropriate postoperative surveillance and perioperative therapeutic strategy.

Methods

A global expression profiling was performed using tissues from GC patients with synchronous liver-confined metastasis. Family with sequence similarity 46, member C (FAM46C), was identified as a candidate biomarker. mRNA expression analysis, direct nucleotide sequencing, bisulfite sequencing and copy number assays for FAM46C were performed with eleven GC cell lines. Expression levels of FAM46C in primary GC tissues from 129 patients who underwent curative GC resection were determined and correlated with clinicopathological factors, including postoperative outcome.

Results

Levels of FAM46C mRNA differed among GC cell lines. Point mutations in FAM46C were detected in five GC cell lines accompanied with reduced FAM46C transcription. No hypermethylation was found in the promoter region of FAM46C. Copy number alterations were found in six GC cell lines with differing FAM46C transcription levels. Reduced FAM46C mRNA expression levels were detected in 117 (91 %) GC specimens compared with adjacent noncancerous tissues. Low FAM46C expression levels were significantly associated with larger macroscopic GC tumor sizes. The low FAM46C expression group was likely to have shorter disease-free survival than the high group and low FAM46C level was identified as an independent risk factor for recurrence after curative resection. FAM46C expression levels were low in all cases that were later found to have hepatic recurrence.

Conclusions

Reduced GC expression of FAM46C is a potential biomarker to predict hepatic recurrence after curative gastrectomy.

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