LAT1 is associated with poor prognosis and radioresistance in head and neck squamous cell carcinoma.
LAT1 is associated with poor prognosis and radioresistance in head and neck squamous cell carcinoma.
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DOI：
10.3892/ol.2023.13757
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发表时间：
2023-04
期刊：
影响因子：
2.9
通讯作者：
Omori Y
中科院分区：
文献类型：
--
作者：
Kawasaki Y;Suzuki H;Miura M;Hatakeyama H;Suzuki S;Yamada T;Suzuki M;Ito A;Omori Y
头颈鳞状细胞癌（HNSCC）已被确定为世界上第六大常见疾病，其预后仍然较差。 HNSCC 的基本治疗包括放化疗和手术相结合。随着免疫检查点抑制剂的出现，预后有所改善；然而，检查点抑制剂的功效有限。 L 型氨基酸转运蛋白 1 (LAT1) 是一种氨基酸转运蛋白，以癌症特异性方式高表达。然而，据我们所知，LAT1 在 HNSCC 中的表达尚未确定。因此，本研究旨在探讨LAT1表达在HNSCC中的作用。总共使用三种 HNSCC 细胞系（Sa3、HSC2 和 HSC4）来研究 LAT1 阳性细胞的特征，包括它们形成球体的能力以及它们的侵袭和迁移。本研究还通过对 2010 年 1 月至 2019 年 12 月期间在秋田大学（日本秋田）诊断、治疗和随访的 174 名患者的活检标本进行免疫染色检查了 LAT1，并进行了总生存期、无进展生存期和多变量分析。结果表明，HNSCC 中的 LAT1 阳性细胞是总生存期和无进展生存期的独立预后因素，并且对放化疗具有抵抗力。因此，LAT1抑制剂JPH203可能有效治疗放化疗耐药的HNSCC，并可能改善HNSCC患者的预后。
Head and neck squamous cell carcinoma (HNSCC) has been identified as the sixth most common disease in the world, and its prognosis remains poor. The basic treatment of HNSCC includes a combination of chemoradiation and surgery. With the advent of immune checkpoint inhibitors, the prognosis has improved; however, the efficacy of checkpoint inhibitors is limited. L-type amino acid transporter 1 (LAT1), an amino acid transporter, is highly expressed in a cancer-specific manner. However, to the best of our knowledge, LAT1 expression in HNSCC has not been determined. Therefore, the present study aimed to examine the role of LAT1 expression in HNSCC. A total of three HNSCC cell lines (Sa3, HSC2 and HSC4) were used to investigate the characteristics of LAT1-positive cells, including their ability to form spheroids, and their invasion and migration. The present study also examined LAT1 by immunostaining of biopsy specimens from 174 patients diagnosed, treated and followed-up at Akita University (Akita, Japan) between January 2010 and December 2019, and overall survival, progression-free survival and multivariate analyses were performed. The results demonstrated that LAT1-positive cells in HNSCC were an independent prognostic factor for overall survival and progression-free survival, and were resistant to chemoradiation. Therefore, JPH203, a LAT1 inhibitor, may be effective in treating chemoradiotherapy-resistant HNSCC and may improve the prognosis of patients with HNSCC.
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影响因子：
8.8
作者：
Kaira, K.;Oriuchi, N.;Imai, H.;Shimizu, K.;Yanagitani, N.;Sunaga, N.;Hisada, T.;Tanaka, S.;Ishizuka, T.;Kanai, Y.;Endou, H.;Nakajima, T.;Mori, M.
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Mori, M.
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1.2
作者：
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Brakenhoff, Ruud H.
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作者：
Oda, Koji;Hosoda, Noriko;Endou, Hitoshi
通讯作者：
Endou, Hitoshi
影响因子：
6.4
作者：
Kaira, Kyoichi;Oriuchi, Noboru;Mori, Masatomo
通讯作者：
Mori, Masatomo
影响因子：
158.5
作者：
Bernier, J;Domenge, C;van Glabbeke, M
通讯作者：
van Glabbeke, M