MAGE-A3 is a prognostic biomarker for poor clinical outcome in cutaneous squamous cell carcinoma with perineural invasion via modulation of cell proliferation.
MAGE-A3 is a prognostic biomarker for poor clinical outcome in cutaneous squamous cell carcinoma with perineural invasion via modulation of cell proliferation.
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DOI：
10.1371/journal.pone.0241551
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发表时间：
2020
期刊：
影响因子：
3.7
通讯作者：
Carucci JA
中科院分区：
文献类型：
--
作者：
Chen A;Santana AL;Doudican N;Roudiani N;Laursen K;Therrien JP;Lee J;Felsen D;Carucci JA
神经周围浸润是肿瘤沿神经扩散并侵入神经的病理过程。神经周围浸润与侵袭性疾病有关，预后不良的可能性更大。在本研究中，9例皮肤鳞状细胞癌伴神经周围浸润的患者中有3例临床预后较差。这些患者的肿瘤表达高水平的MAGE-A3，这是一种可能参与肿瘤发展关键过程的癌睾丸抗原。除神经周围浸润外，肿瘤表现为分化差和深部浸润，随后被布莱根妇女医院分类为肿瘤3期。肿瘤组织Cyclin E、A、B mRNA水平较正常皮肤组织升高（分别为102.93±15.03∶27.15±4.59、36.83±19.41∶11.59±5.83、343.77±86.49∶95.65±29.25,p<0.05）。经MAGE-A3抗体预处理的A431皮肤鳞状细胞癌细胞的s期细胞比例降低（14.13±2.8%比33.97±1.1%,p<0.05），划痕实验的闭合率降低（43.88±5.49%比61.17±3.97%,p = 0.0058）。在鳞状细胞癌的同基因动物模型中，免疫印迹显示肿瘤在6周时过度表达MAGE-A3和细胞周期蛋白E、a和B。然而，与亲代细胞相比，敲除MAGE-A3表达导致肿瘤生长减少（平均肿瘤体积155.3 mm3比3.2 mm3）。这些结果表明MAGE-A3是癌症进展的关键介质。与正常皮肤组织相比，低分化皮肤鳞状细胞癌伴神经周围浸润的胶原蛋白XI和基质金属蛋白酶3、10、11、13 mRNA水平升高（分别为1132.56±882.7 vs. 107.62±183.62,1118.15±1109.49 vs. 9.5±5,2603.87±2385.26 vs. 5.29±3,957.95±627.14 vs. 400.42±967.66,1149.13±832.18 vs. 19.41±35.62,p<0.05）。总之，本研究强调了MAGE-A3在皮肤鳞状细胞癌患者临床预后中的潜在预后价值。
Perineural invasion is a pathologic process of neoplastic dissemination along and invading into the nerves. Perineural invasion is associated with aggressive disease and a greater likelihood of poor outcomes. In this study, 3 of 9 patients with cutaneous squamous cell carcinoma and perineural invasion exhibited poor clinical outcomes. Tumors from these patients expressed high levels of MAGE-A3, a cancer testis antigen that may contribute to key processes of tumor development. In addition to perineural invasion, the tumors exhibited poor differentiation and deep invasion and were subsequently classified as Brigham and Women’s Hospital tumor stage 3. Cyclin E, A and B mRNA levels were increased in these tumors compared with normal skin tissues (102.93±15.03 vs. 27.15±4.59, 36.83±19.41 vs. 11.59±5.83, 343.77±86.49 vs. 95.65±29.25, respectively; p<0.05). A431 cutaneous squamous cell carcinoma cells pretreated with MAGE-A3 antibody exhibited a decreased percentage S-phase cells (14.13±2.8% vs. 33.97±1.1%; p<0.05) and reduced closure in scratch assays (43.88±5.49% vs. 61.17±3.97%; p = 0.0058). In a syngeneic animal model of squamous cell carcinoma, immunoblots revealed overexpression of MAGE-A3 and cyclin E, A, and B protein in tumors at 6 weeks. However, knockout of MAGE-A3 expression caused a reduction in tumor growth (mean tumor volume 155.3 mm3 vs. 3.2 mm3) compared with parental cells. These results suggest that MAGE-A3 is a key mediator in cancer progression. Moreover, elevated collagen XI and matrix metalloproteases 3, 10, 11, and 13 mRNA levels were observed in poorly differentiated cutaneous squamous cell carcinoma with perineural invasion compared with normal skin tissue (1132.56±882.7 vs. 107.62±183.62, 1118.15±1109.49 vs. 9.5±5, 2603.87±2385.26 vs. 5.29±3, 957.95±627.14 vs. 400.42±967.66, 1149.13±832.18 vs. 19.41±35.62, respectively; p<0.05). In summary, this study highlights the potential prognostic value of MAGE-A3 in clinical outcomes of cutaneous squamous cell carcinoma patients.
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Cyclin E 转基因小鼠：肺癌生物学、治疗和预防的发现工具。
DOI：
10.1158/1940-6207.capr-10-0297
发表时间：
2010-12
期刊：
Cancer prevention research (Philadelphia, Pa.)
影响因子：
--
作者：
Freemantle SJ;Dmitrovsky E
通讯作者：
Dmitrovsky E
影响因子：
13.8
作者：
Karia, Pritesh S.;Han, Jiali;Schmults, Chrysalyne D.
通讯作者：
Schmults, Chrysalyne D.
影响因子：
--
作者：
Elliott, MJ;Baker, JD;McMasters, KM
通讯作者：
McMasters, KM
影响因子：
15.9
作者：
Conacci-Sorrell, M;Zhurinsky, J;Ben-Ze'ev, A
通讯作者：
Ben-Ze'ev, A
影响因子：
2.9
作者：
Jia, Binghan;Zhao, Xiaoling;Yang, Yuemei
通讯作者：
Yang, Yuemei