Field effect in
cancer, also called "field cancerization", attempts to explain the development of multiple primary
tumors and locally recurrent
cancer. The concept of field effect in
cancer has been reinforced, since molecular alterations were found in
tumor-adjacent tissues with normal histopatho-logical appearances. With the aim of investigating field effects in
gastric cancer (GC), we conducted a high-throughput sequencing of the miRnome of four GC samples and their respective
tumor-adjacent tissues and compared them with the miRnome of a gastric antrum sample from patients without GC, assuming that
tumor-adjacent tissues could not be considered as normal tissues. The global number of
miRNAs and read counts was highest in
tumor samples, followed by
tumor-adjacent and normal samples. Analyzing the
miRNA expression profile of
tumor-adjacent
miRNA,
hsa-miR-3131,
hsa-miR-664,
hsa-miR-483, and
hsa-miR-150 were significantly downregulated compared with the antrum without
tumor tissue (P-value < 0.01; fold-change <5). Additionally,
hsa-miR-3131,
hsa-miR-664, and
hsa-miR-150 were downregulated (P-value < 0.001) in all paired samples of
tumor and
tumor-adjacent tissues, compared with antrum without
tumor mucosa. The field effect was clearly demonstrated in gastric
carcinogenesis by an epigenetics-based approach, and potential
biomarkers of the GC field effect were identified. The elevated expression of
miRNAs in adjacent tissues and
tumors tissues may indicate that a cascade of events takes place during gastric
carcinogenesis, reinforcing the notion of field effects. This phenomenon seems to be linked to DNA methylation patterns in
cancer and suggests the involvement of an epigenetic network mechanism.