Kawasaki Yohei, Suzuki Hitomi, Miura Masahito, Hatakeyama Haruka, Suzuki Shinsuke, Yamada Takechiyo, Suzuki Maya, Ito Ayumi, Omori Yasufumi
Department of Otorhinolaryngology and Head-and-Neck Surgery, Akita University Graduate School of Medicine, Akita, Akita 010-8543, Japan.
Department of Molecular and Tumour Pathology, Akita University Graduate School of Medicine, Akita, Akita 010-8543, Japan.
Oncol Lett. 2023 Mar 13;25(4):171. doi: 10.3892/ol.2023.13757. eCollection 2023 Apr.
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.
头颈部鳞状细胞癌（HNSCC）已被确定为全球第六大常见疾病，其预后仍然很差。HNSCC的基本治疗包括放化疗和手术联合。随着免疫检查点抑制剂的出现，预后有所改善；然而，检查点抑制剂的疗效有限。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度表达。然而，据我们所知，HNSCC中LAT1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。总共使用了三种HNSCC细胞系（Sa3、HSC2和HSC4）来研究LAT1阳性细胞的特性，包括它们形成球体的能力以及侵袭和迁移能力。本研究还通过对2010年1月至2019年12月在日本秋田大学诊断、治疗和随访的174例患者的活检标本进行免疫染色来检测LAT1，并进行总生存、无进展生存和多变量分析。结果表明，HNSCC中的LAT1阳性细胞是总生存和无进展生存的独立预后因素，并且对放化疗耐药。因此，LAT1抑制剂JPH203可能对治疗放化疗耐药的HNSCC有效，并可能改善HNSCC患者的预后。
