Endosomal protein expression of γ1-adaptin is associated with tumor growth activity and relapse-free survival in breast cancer.

IF 4 3区医学 Q1 OBSTETRICS & GYNECOLOGY

Breast Cancer Pub Date : 2024-03-01 Epub Date: 2024-01-24 DOI:10.1007/s12282-023-01539-1

Nobuhiro Hoshi, Takefumi Uemura, Kazunoshin Tachibana, Sadahiko Abe, Yuko Murakami-Nishimagi, Maiko Okano, Masaru Noda, Katsuharu Saito, Koji Kono, Tohru Ohtake, Satoshi Waguri

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引用次数: 0

Abstract

Background: γ1-Adaptin is a subunit of adaptor protein complex-1 (AP-1), which regulates intracellular transport between the trans-Golgi network (TGN) and endosomes. Since expression levels of AP-1 subunits have been reported to be associated with cell proliferation and cancer malignancy, we investigated the relationships between the immunohistochemical expression of γ1-adaptin and both clinicopathological factors and relapse-free survival (RFS) in breast cancer tissue.

Materials and methods: SK-BR-3 cell line depleted of γ1-adaptin was used for cell proliferation, migration, and invasion assay. Intracellular localization of γ1-adaptin was examined with immunohistochemistry (IHC) using an antibody against γ1-adaptin, and with double immunohistofluorescence (IHF) microscopy using markers for the TGN and endosome. γ1-Adaptin intensities in IHC samples from 199 primary breast cancer patients were quantified and assessed in relation to clinicopathological factors and RFS.

Results: Cell growth, migration, and invasion of SK-BR-3 cells were significantly suppressed by the depletion of γ1-adaptin. Although the staining patterns in the cancer tissues varied among cases by IHC, double IHF demonstrated that γ1-adaptin was mainly localized in EEA1-positive endosomes, but not in the TGN. γ1-Adaptin intensity was significantly higher in the tumor regions than in non-tumor regions. It was also higher in patients with Ki-67 (high), ER (-), PgR (-), and HER2 (+). Among subtypes of breast cancer, γ1-adaptin intensity was higher in HER2 than in luminal A or luminal B. The results of the survival analysis indicated that high γ1-adaptin intensity was significantly associated with worse RFS, and this association was also observed in group with ER (+), PgR (+), HER2 (-), Ki-67 (high), or luminal B. In addition, the Cox proportional hazards model showed that high γ1-adaptin intensity was an independent prognostic factor.

Conclusion: These results suggest that the endosomal expression of γ1-adaptin is positively correlated with breast cancer malignancy and could be a novel prognostic marker.

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γ1-adaptin的内体蛋白表达与乳腺癌的肿瘤生长活性和无复发生存率有关。

背景：γ1-Adaptin是适应蛋白复合物-1（AP-1）的一个亚基，AP-1调节跨高尔基体网络（TGN）和内体之间的胞内转运。据报道，AP-1亚基的表达水平与细胞增殖和癌症恶性程度有关，因此我们研究了乳腺癌组织中γ1-adaptin的免疫组化表达与临床病理因素和无复发生存率（RFS）之间的关系：使用去除了γ1-adaptin的SK-BR-3细胞系进行细胞增殖、迁移和侵袭试验。使用针对γ1-adaptin的抗体进行免疫组化（IHC），并使用TGN和内质体标记物进行双重免疫组化荧光（IHF）显微镜检查γ1-adaptin的胞内定位。对199名原发性乳腺癌患者IHC样本中的γ1-Adaptin强度进行了量化，并评估了其与临床病理因素和RFS的关系：结果：消耗γ1-adaptin可显著抑制SK-BR-3细胞的生长、迁移和侵袭。虽然不同病例癌组织的 IHC 染色模式不同，但双 IHF 显示γ1-adaptin 主要定位于 EEA1 阳性内体，而不在 TGN 中。肿瘤区域的γ1-Adaptin强度明显高于非肿瘤区域。Ki-67（高）、ER（-）、PgR（-）和HER2（+）患者的γ1-Adaptin强度也更高。生存分析结果表明，γ1-adaptin强度高与RFS恶化显著相关，在ER（+）、PgR（+）、HER2（-）、Ki-67（高）或管腔B组中也观察到了这种关联：这些结果表明，γ1-adaptin的内体表达与乳腺癌的恶性程度呈正相关，可作为一种新的预后标志物。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Breast Cancer ONCOLOGY-OBSTETRICS & GYNECOLOGY

CiteScore

6.70

自引率

2.50%

发文量

105

审稿时长

6-12 weeks

期刊介绍： Breast Cancer, the official journal of the Japanese Breast Cancer Society, publishes articles that contribute to progress in the field, in basic or translational research and also in clinical research, seeking to develop a new focus and new perspectives for all who are concerned with breast cancer. The journal welcomes all original articles describing clinical and epidemiological studies and laboratory investigations regarding breast cancer and related diseases. The journal will consider five types of articles: editorials, review articles, original articles, case reports, and rapid communications. Although editorials and review articles will principally be solicited by the editors, they can also be submitted for peer review, as in the case of original articles. The journal provides the best of up-to-date information on breast cancer, presenting readers with high-impact, original work focusing on pivotal issues.