Teasing out the best molecular marker in the AKT/mTOR pathway in head and neck squamous cell cancer patients.
Teasing out the best molecular marker in the AKT/mTOR pathway in head and neck squamous cell cancer patients.
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DOI：
10.1002/lary.20917
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发表时间：
2010-06
期刊：
影响因子：
2.6
通讯作者：
Nathan, Cherie-Ann O.
中科院分区：
文献类型：
--
作者：
Clark, Cheryl;Shah, Shivang;Herman-Ferdinandez, Lilantha;Ekshyyan, Oleksandr;Abreo, Fleurette;Rong, Xiaohua;McLarty, Jerry;Lurie, Aubrey;Milligan, Edward J.;Nathan, Cherie-Ann O.
目前没有可靠的分子生物标志物可用于头颈部癌症患者的临床应用。AKT/MTOR通路在90-100%的HNSCC中被激活，可能是与癌症发病率密切相关的有前途的生物标志物。将来自非癌症患者的口腔粘膜与HNSCC肿瘤和交界区粘膜进行比较。使用免疫组织化学（IHC）和蛋白质印迹法评价候选生物标志物MTOR、AKT、4 EBP 1和S6激酶、在HNSCC中出现失调的MTOR上游和下游信号传导组分。通过蛋白质印迹，与非癌症口腔粘膜样品相比，癌症患者肿瘤中磷酸化AKT和磷酸化MTOR的表达显著更高（分别为p=0.004和p=0.026）。与肿瘤相比，pMTOR和p4 EBP 1在患者结合区中的表达更高（分别为p=0.017和p=0.022），并且与肿瘤相比，HNSCC患者的结合区中的p-AKT或p-S6表达没有差异。p-MTOR表达在鉴别癌与非癌粘膜中的敏感性为81.9%，特异性为100%，而p-4 EBP 1表达在鉴别正常粘膜与HNSCC中的敏感性仅为50.0%，特异性为95.5%（p<0.01）。在人头颈癌中，通过蛋白质免疫印迹（p=0.026）和IHC（p<0.001），磷酸化MTOR似乎是可靠的生物标志物。此外，磷酸化AKT，这是直接上游的MTOR，是一个潜在的生物标志物，应进一步研究。正在评估HNSCC的MTOR抑制剂的临床试验，选择可能对这些抑制剂有反应的患者需要鉴定和验证反应的预测生物标志物。
No reliable molecular biomarker is currently available for clinical application in the management of head and neck cancer patients. The AKT/MTOR pathway is activated in 90-100% of HNSCC and could be promising biomarkers closely linked to cancer incidence. Oral mucosa from non-cancer patients were compared to HNSCC tumors and junctional zone mucosa. The candidate biomarkers MTOR, AKT, 4EBP1, and S6 kinase, signaling components upstream and downstream of MTOR that appear dysregulated in HNSCC were evaluated using immunohistochemistry (IHC) and western blot. Expression of phosphorylated AKT and phosphorylated MTOR were significantly higher in cancer patient tumors compared to non-cancer oral mucosa samples (p=0.004 and p=0.026 respectively) by western. pMTOR and p4EBP1 expression were higher in patient junctional zones compared to tumors (p=0.017 and p=0.022 respectively) and no difference in p-AKT or p-S6 expression in HNSCC patients' junctional zone compared to tumors. IHC demonstrated p-MTOR expression was 81.9% sensitive and 100% specific in differentiating cancer from non-cancer mucosa, while p-4EBP1 expression by IHC was only 50.0% sensitive and 95.5% specific in differentiating normal mucosa from HNSCC (p<0.01). Phosphorylated MTOR appears to be a reliable biomarker by both western (p=0.026) and IHC in human head and neck cancer (p<0.001). Moreover, phosphorylated AKT, which is immediately upstream of MTOR, is a potential biomarker that should be further studied. Clinical trials with MTOR inhibitors are being evaluated for HNSCC, and selecting patients that are likely to respond to these inhibitors requires identifying and validating predictive biomarkers of response.
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影响因子：
11.2
作者：
Nathan, Cherie-Ann O.;Amirghahari, Nazanin;Caldito, Gloria
通讯作者：
Caldito, Gloria
影响因子：
4
作者：
Huang, S;Houghton, PJ
通讯作者：
Houghton, PJ
DOI：
10.1093/jnci/djn389
发表时间：
2008-12-03
期刊：
Journal of the National Cancer Institute
影响因子：
--
作者：
Jemal A;Thun MJ;Ries LA;Howe HL;Weir HK;Center MM;Ward E;Wu XC;Eheman C;Anderson R;Ajani UA;Kohler B;Edwards BK
通讯作者：
Edwards BK
影响因子：
2.6
作者：
Nathan, CAO;Amirghahri, N;Stucker, FJ
通讯作者：
Stucker, FJ
影响因子：
2.6
作者：
Nathan, CAO;Franklin, S;Stucker, FJ
通讯作者：
Stucker, FJ