Prognostic significance of LDL receptor-related protein 1B in patients with gastric cancer

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 pr...

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Bibliographic Details
Published in:	Journal of molecular histology 2021-04, Vol.52 (2), p.165-172
Main Authors:	Yasufuku, Itaru, Saigo, Chiemi, Kito, Yusuke, Yoshida, Kazuhiro, Takeuchi, Tamotsu
Format:	Article
Language:	eng
Subjects:	Adult Aged Aged, 80 and over Biomedical and Life Sciences Biomedicine Carcinogenesis Cell Biology Developmental Biology Endocytosis Epigenetics Female Gastric cancer Gene expression Humans Immunohistochemistry Immunoreactivity Internalization Intestine Life Sciences Localization Low density lipoprotein Low density lipoprotein receptors LRP1B protein Male Middle Aged Original Paper Prognosis Protein turnover Proteins Receptors, LDL - genetics Receptors, LDL - metabolism Retrospective Studies Stomach cancer Stomach Neoplasms - genetics Stomach Neoplasms - metabolism Stomach Neoplasms - pathology
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Summary:	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.
ISSN:	1567-2379 1567-2387