Suenaga Masaya, Yamada Suguru, Fuchs Bryan C, Fujii Tsutomu, Kanda Mitsuro, Tanaka Chie, Kobayashi Daisuke, Fujiwara Michitaka, Tanabe Kenneth K, Kodera Yasuhiro
Department of Gastroenterological Surgery (Surgery II), Nagoya University Graduate School of Medicine, Nagoya, Japan.
Division of Surgical Oncology, Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, Massachusetts.
J Surg Oncol. 2015 Nov;112(6):622-8. doi: 10.1002/jso.24056. Epub 2015 Sep 28.
The clinical implications of single nucleotide polymorphisms (SNPs) in CD44 remain unclear. This study examined the relationships of CD44 SNPs with clinicopathological parameters and prognosis in Japanese gastric cancer patients.
The CD44 SNPs were analyzed in 11 gastric cancer cell lines and 517 clinical specimens. The expression of CD44 standard (CD44s) and CD44 variant 9 isoform (CD44v9) transcripts were measured by quantitative real-time polymerase chain reaction.
The CD44 rs187116 A/A, A/G, and G/G genotypes were present in 10.3%, 45.1%, and 44.7% of patients, respectively. The presence of CD44 rs187116 A/G or G/G genotypes was significantly associated with positive peritoneal washing cytology (P = 0.012). Disease-free survival of patients with these genotypes was significantly worse than in those with the A/A genotype (P = 0.039). Multivariate analysis showed that the CD44 rs187116 was independently prognostic of disease-free survival (P = 0.047). The CD44s/CD44v9 ratio was significantly lower in patients with the CD44 rs187116 A/A genotype than in those with the A/G (P = 0.046) and G/G (P = 0.047) genotypes.
The CD44 rs187116 genotype could predict disease recurrence in Japanese gastric cancer patients, and the SNP was associated with CD44 isoform switching.
CD44单核苷酸多态性(SNP)的临床意义尚不清楚。本研究探讨了日本胃癌患者中CD44 SNP与临床病理参数及预后的关系。
对11种胃癌细胞系和517份临床标本进行CD44 SNP分析。通过定量实时聚合酶链反应检测CD44标准型(CD44s)和CD44变异体9亚型(CD44v9)转录本的表达。
CD44 rs187116的A/A、A/G和G/G基因型分别出现在10.3%、45.1%和44.7%的患者中。CD44 rs187116 A/G或G/G基因型的存在与腹腔冲洗液细胞学阳性显著相关(P = 0.012)。这些基因型患者的无病生存期明显差于A/A基因型患者(P = 0.039)。多因素分析显示,CD44 rs187116是无病生存期的独立预后因素(P = 0.047)。CD44 rs187116 A/A基因型患者的CD44s/CD44v9比值显著低于A/G基因型(P = 0.046)和G/G基因型(P = 0.047)患者。
CD44 rs187116基因型可预测日本胃癌患者的疾病复发,且该SNP与CD44亚型转换有关。