Yamamoto Masaaki, Takahashi Tsuyoshi, Serada Satoshi, Sugase Takahito, Tanaka Koji, Miyazaki Yasuhiro, Makino Tomoki, Kurokawa Yukinori, Yamasaki Makoto, Nakajima Kiyokazu, Takiguchi Shuji, Naka Testsuji, Mori Masaki, Doki Yuichiro
Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, Osaka, Japan.
Laboratory of Immune Signal, National Institute of Biomedical Innovation, Health and Nutrition, Osaka, Japan.
Cancer Sci. 2017 Oct;108(10):2052-2060. doi: 10.1111/cas.13329.
Gastric cancer is one of the most common malignant tumors. Although improvement in chemotherapy has been achieved, the clinical prognosis of advanced gastric cancer remains poor. Therefore, it is increasingly important to predict the prognosis and determine whether patients should or should not receive neoadjuvant or adjuvant chemotherapy. Leucine-rich α2-glycoprotein-1 (LRG1) is overexpressed during inflammation and is associated with various malignancies. In this study, we assessed LRG1 expression in cancer specimens and in the sera of patients with cancer to clarify the usefulness of LRG1 as a biomarker in gastric cancer. This study enrolled 239 (for immunohistochemical staining; IHC) and 184 (for ELISA) patients with gastric cancer. Results of IHC showed that LRG1 expression was significantly associated with histological type, lymphatic and venous invasion, tumor and node factors, and disease stage. Overall survival was significantly worse in the high LRG1 expression group than in the low LRG1 group (P = 0.0003). Cox multivariate analysis of overall survival revealed that LRG1 expression was an independent prognostic factor (P = 0.0258). Serum LRG1 was significantly higher in gastric cancer patients than in healthy volunteers, and increased as the pathological stage progressed. Furthermore, a significant correlation was revealed between serum LRG1 level and LRG1 expression with IHC (P < 0.0001). Inhibition of LRG1 significantly decreased cell proliferation in vitro (migratory and invasive capacity of gastric cancer cells). These results suggest that LRG1 expression in tumors and serum may be a useful prognostic marker in gastric cancer patients.
胃癌是最常见的恶性肿瘤之一。尽管化疗已取得进展，但晚期胃癌的临床预后仍然很差。因此，预测预后并确定患者是否应接受新辅助或辅助化疗变得越来越重要。富含亮氨酸的α2-糖蛋白-1（LRG1）在炎症期间过度表达，并与多种恶性肿瘤相关。在本研究中，我们评估了LRG1在癌症标本和癌症患者血清中的表达，以阐明LRG1作为胃癌生物标志物的实用性。本研究纳入了239例（用于免疫组织化学染色；IHC）和184例（用于ELISA）胃癌患者。IHC结果显示，LRG1表达与组织学类型、淋巴和静脉侵犯、肿瘤和淋巴结因素以及疾病分期显著相关。LRG1高表达组的总生存期明显低于LRG1低表达组（P = 0.0003）。对总生存期的Cox多因素分析显示，LRG1表达是一个独立的预后因素（P = 0.0258）。胃癌患者血清LRG1明显高于健康志愿者，并随着病理分期的进展而升高。此外，血清LRG1水平与IHC检测的LRG1表达之间存在显著相关性（P < 0.0001）。抑制LRG1可显著降低体外细胞增殖（胃癌细胞的迁移和侵袭能力）。这些结果表明，肿瘤和血清中的LRG1表达可能是胃癌患者有用的预后标志物。
