Multiple genetic alterations are attributed to gastric cancer (GC); however, only a few critical genes have been identified so far. In this study, we isolated and characterized a novel gene p42.3, represented as tumor-specific and mitosis phase-dependent expression protein in GC cell line BGC823. Our data showed that the expression of p42.3 was cell cycle-dependent in GC cell lines. Moreover, p42.3 was specifically expressed in primary GC tissues but not in the matched normal mucosa of stomach, and this gene was expressed in diverse embryonic tissues. Furthermore, significant suppression of cell proliferation and tumorigenicity were detected and G 2 /M phase arrest was observed in cell line BGC823 depleted of p42.3 expression by RNAi technique, and we confirmed the expression changes of cyclin B1 and Chk2 following the silence of p42.3. Taken together, we cloned and characterized p42.3 gene that was specifically expressed in GC tumors but not in normal gastric mucosa, and the gene was associated with M-phase regulation. Moreover, p42.3 might be involved in cell proliferation and tumorigenesis; therefore, this gene might have potential applications in the diagnosis or treatment of GC.

Nude mice are important in vivo model for characterization of cell malignancy behavior; however, many cancer cells fail to form tumors in it. Understanding this defective mechanism may provide novel insights into tumorigenesis and how tumor cells escape innate immunity. Whole-genome sequencing was conducted on two gastric cancer (GC) cells, BGC823 and AGS, which do and do not form tumors in nude mice, to identify their genomic differences relevant to natural killer (NK) cells. We found that the tumorigenic capacity of human GC cell lines was dependent on the recruitment and activation of NK cells in xenograft tumors. We used whole-genome sequence (WGS) on GC cell lines to identify potential genes controlling susceptibility to NK-mediated killing. The tumorigenic cell line BGC823 expressed high levels of HLA-I because of copy gain and was resistant to NK cell killing. In contrast, another cell line AGS expressing low levels of HLA-I with activated NKp30/MAPK/IL-12 (interleukin-12) or IL-2 (interleukin-2) pathway was susceptible to NK lysis. Treatment of tumor bearing mice with systemic administration of IL-12 in combination with intratumor injection of anti-HLA-I antibody significantly increased NK cell recruitment into xenograft tumors, which became sensitive to NK killing, resulting in reduced tumor progression. In human GC specimens, decreased HLA-I expression and increased NK cells surrounding tumor cells were correlated with decreased metastasis potential and better prognosis of patients. Our results provide a mechanistic basis for GC cells to escape NK lysis and a promising prospect of NK immunotherapy for GC cells.