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LAMTOR5 的高表达预示着不良预后,并与头颈部鳞状细胞癌的淋巴结转移相关。

Increased Expression of LAMTOR5 Predicts Poor Prognosis and Is Associated with Lymph Node Metastasis of Head and Neck Squamous Cell Carcinoma.

机构信息

The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) & Key Laboratory of Oral Biomedicine Ministry of Education, School and Hospital of Stomatology, Wuhan University, Wuhan, China.

Department of Oral and Maxillofacial Head Neck Oncology, School & Hospital of Stomatology, Wuhan University, Wuhan, China.

出版信息

Int J Med Sci. 2019 Jun 2;16(6):783-792. doi: 10.7150/ijms.33415. eCollection 2019.

Abstract

Late endosomal/lysosomal adaptor and MAPK and mTOR activator 5 (LAMTOR5) is a novel oncoprotein associated with several human malignancies, but its clinical role in head and neck squamous cell carcinoma (HNSCC) remains unclear. The present study aims to investigate the clinical and pathological significance of LAMTOR5 in HNSCC. We utilized immunohistochemical staining of human tissue microarrays (210 primary HNSCC, 42 normal oral mucosae, 69 oral epithelial dysplasia, and 68 metastasis lymph nodes) to explore the clinical and pathological significance of LAMTOR5 in HNSCC. Additionally, expression level of LAMTOR5 in immunoreactivity of conditional knock out ( cKO) mice HNSCC was also assessed. We found LAMTOR5 was overexpressed in human and cKO mice HNSCC, and its expression was significantly associated with patients' overall survival, lymph node metastasis and lymph node grade. Furthermore, LAMTOR5 expression was significantly correlated with the expression of p-Akt, p-S6, immune checkpoints (PD-L1, Galectin 9, VISTA and B7-H4) and macrophage markers (CD68 and CD163). In cKO mice HNSCC, it was also significantly correlated with VISTA and F4/80. Consequently, we consider that high expression of LAMTOR5 might be a poor prognostic indicator and correlated with the immunosuppression of tumor microenvironment.

摘要

晚期内体/溶酶体衔接和 MAPK 和 mTOR 激活物 5(LAMTOR5)是一种与多种人类恶性肿瘤相关的新型癌蛋白,但它在头颈部鳞状细胞癌(HNSCC)中的临床作用尚不清楚。本研究旨在探讨 LAMTOR5 在 HNSCC 中的临床和病理意义。我们利用免疫组织化学染色的人类组织微阵列(210 例原发性 HNSCC、42 例正常口腔黏膜、69 例口腔上皮异型增生和 68 例转移淋巴结)来探讨 LAMTOR5 在 HNSCC 中的临床和病理意义。此外,还评估了条件敲除(cKO)小鼠 HNSCC 中 LAMTOR5 的表达水平。我们发现 LAMTOR5 在人源和 cKO 小鼠 HNSCC 中过表达,其表达与患者的总生存期、淋巴结转移和淋巴结分级显著相关。此外,LAMTOR5 的表达与 p-Akt、p-S6、免疫检查点(PD-L1、半乳糖凝集素 9、VISTA 和 B7-H4)和巨噬细胞标志物(CD68 和 CD163)的表达显著相关。在 cKO 小鼠 HNSCC 中,它还与 VISTA 和 F4/80 显著相关。因此,我们认为 LAMTOR5 的高表达可能是预后不良的指标,并与肿瘤微环境的免疫抑制有关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/316b/6643113/9686a6094932/ijmsv16p0783g001.jpg

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