LDLR-related protein 1B (LRP1B) is believed to internalize ligands through receptor-mediated endocytosis. Previous epigenetic and genetic studies have indicated that impaired LRP1B mRNA expression might be related to gastric carcinogenesis. However, expression and prognostic significance of LRP1B protein remain to be elucidated. This study aimed to unravel the clinicopathological characteristics of LRP1B protein expression in gastric cancer. Immunohistochemical staining with antibodies specific to LRP1B peptide, which has an EXXXLL motif-containing region in the C-terminal flexible loop for intracellular sorting, was performed with 100 gastric cancer tissue specimens. Out of 100 tissue specimens, 45 exhibited cytoplasmic localization of LRP1B immunoreactivity. This cytoplasmic localization of LRP1B was significantly higher (P = 0.044) in intestinal-type gastric cancer (25 of 44) than in diffuse-type gastric cancer (20 of 56). Notably, cytoplasmic LRP1B immunoreactivity was significantly associated with low clinicopathological stage and favorable prognosis of patients with diffuse-type gastric cancer (P = 0.014), but nor with intestinal-type gastric cancer (P = 0.994). Multivalent analysis revealed that cytoplasmic LRP1B immunoreactivity had an independent favorable prognostic value in diffuse-type gastric cancer (P = 0.046; hazard ratio 3.058, 95% confidence interval 1.022–9.149). In contrast, no significant relation of cytoplasmic LRP1B immunoreactivity to patients’ prognosis was found in intestinal-type gastric cancer. Double immunocytochemical staining demonstrated that cytoplasmic LRP1B was co-localized with RAB11FIP1, which constituted the endocytic recycling compartments in diffuse-type gastric cancer cells. The findings of this study indicated that impaired endocytosis of the cytoplasmic domain of LRP1B, resulting in insufficient ligand internalization, is related to poor prognosis of patients with diffuse-type gastric cancer.

LDLR 相关蛋白 1B (LRP1B) 被认为通过受体介导的内吞作用使配体内化。先前的表观遗传学和遗传学研究表明，LRP1B受损mRNA表达可能与胃癌发生有关。然而，LRP1B 蛋白的表达和预后意义仍有待阐明。本研究旨在阐明胃癌中 LRP1B 蛋白表达的临床病理特征。对 100 个胃癌组织标本进行了免疫组织化学染色，LRP1B 肽的抗体在 C 端柔性环中有一个包含 EXXXLL 基序的区域，用于细胞内分选。在 100 个组织标本中，45 个表现出 LRP1B 免疫反应性的细胞质定位。LRP1B 的这种细胞质定位显着更高（P = 0.044) 在肠型胃癌（44 个中的 25 个）中比在弥漫型胃癌中（56 个中的 20 个）。值得注意的是，细胞质 LRP1B 免疫反应性与弥漫型胃癌患者的低临床病理分期和良好预后显着相关（P  = 0.014），但与肠型胃癌（P  = 0.994）无关。多价分析显示，细胞质 LRP1B 免疫反应性在弥漫型胃癌中具有独立的有利预后价值（P = 0.046; 风险比 3.058，95% 置信区间 1.022–9.149）。相比之下，在肠型胃癌中未发现细胞质 LRP1B 免疫反应性与患者预后的显着关系。双免疫细胞化学染色表明细胞质 LRP1B 与 RAB11FIP1 共定位，RAB11FIP1 构成弥漫型胃癌细胞的内吞回收区室。本研究的结果表明，LRP1B 细胞质结构域的内吞作用受损，导致配体内化不足，与弥漫型胃癌患者的预后不良有关。