Prognostic significance of amino-acid transporter expression (LAT1, ASCT2, and xCT) in surgically resected tongue cancer.

Prognostic significance of amino-acid transporter expression (LAT1, ASCT2, and xCT) in surgically resected tongue cancer.
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DOI:
10.1038/bjc.2014.178
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发表时间:
2014-05-13
影响因子:
8.8
通讯作者:
Chikamatsu, K.
Chikamatsu, K.
中科院分区:
医学1区
文献类型:
--
作者:
Toyoda, M.;Kaira, K.;Ohshima, Y.;Ishioka, N. S.;Shino, M.;Sakakura, K.;Takayasu, Y.;Takahashi, K.;Tominaga, H.;Oriuchi, N.;Nagamori, S.;Kanai, Y.;Oyama, T.;Chikamatsu, K.

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氨基酸转运体是肿瘤细胞生长和存活所必需的,在癌细胞的生长和侵袭过程中起着至关重要的作用。但目前尚不清楚L氨基酸转运蛋白1(LAT1)、系统天冬氨酸转运蛋白2(ASCT2)和XCT在舌癌中的表达及其预后意义。我们进行了临床病理研究,以了解这些氨基酸转运体在舌癌中的蛋白表达。对85例经手术切除的舌癌患者进行了评估。采用免疫组织化学方法检测LAT1、ASCT2、XCT、4F2hc/CD98hc(4F2hc)、Ki-67和CD34、P53检测微血管密度(MVD)。L型氨基酸转运蛋白1和4F2hc的高表达分别为61.0%(52/85)和45%(38/47)。ASC氨基酸转运蛋白-2和XCT的阳性表达分别为59%(50/85)和21%(18/85)。LAT1和ASCT2的表达与肿瘤分期、淋巴结转移、淋巴渗透、4F2hc表达和细胞增殖(Ki-67)显著相关。XCT的表达与晚期和肿瘤因素显著相关。单因素分析显示,LAT1、ASCT2、4F2hc、Ki-67、淋巴渗透、血管侵犯与总生存率有显著关系。多因素分析证实LAT1是预测预后不良的独立预后因素。L型氨基酸转运体1和ASCT2可作为预测舌癌手术后不良预后的重要预后因子,在舌癌的发生、发展和侵袭性中可能起重要作用。
Amino-acid transporters are necessary for the tumour cell growth and survival, and have a crucial role in the development and invasiveness of cancer cells. But, it remains unclear about the prognostic significance of L-type amino-acid transporter 1 (LAT1), system ASC amino-acid transporter-2 (ASCT2), and xCT expression in patients with tongue cancer. We conducted the clinicopathological study to investigate the protein expression of these amino-acid transporters in tongue cancer. Eighty-five patients with surgically resected tongue cancer were evaluated. Tumour sections were stained by immunohistochemistry for LAT1, ASCT2, xCT, 4F2hc/CD98hc (4F2hc), Ki-67, and microvessel density (MVD) determined by CD34, and p53. L-type amino-acid transporter 1 and 4F2hc were highly expressed in 61% (52 out of 85) and 45% (38 out of 47), respectively. ASC amino-acid transporter-2 and xCT were positively expressed in 59% (50 out of 85) and 21% (18 out of 85), respectively. The expression of both LAT1 and ASCT2 was significantly associated with disease staging, lymph-node metastasis, lymphatic permeation, 4F2hc expression and cell proliferation (Ki-67). xCT expression indicated a significant association with advanced stage and tumour factor. By univariate analysis, disease staging, lymphatic permeation, vascular invasion, LAT1, ASCT2, 4F2hc, and Ki-67 had a significant relationship with overall survival. Multivariate analysis confirmed that LAT1 was an independent prognostic factor for predicting poor prognosis. L-type amino-acid transporter 1 and ASCT2 can serve as a significant prognostic factor for predicting worse outcome after surgical treatment and may have an important role in the development and aggressiveness of tongue cancer.
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