口腔鳞状细胞癌发病率在所有颈部和头部癌症患者总人数中大约占有1/4的比例。它是癌症引起死亡的主要因素—主要是由于目前没有有效的组织检查方法预测癌症是否会复发。
在最新一期的《BMC Cancer》杂志上，科学家们发现有四种基因的表达可以准确的预测患者复发口腔鳞状细胞癌的风险。[A gene signature in histologically normal surgical margins is predictive of oral carcinoma recurrence.BMC Cancer.11. October 2011]
来自加拿大安大略湖癌症中心的，由Suzanne Kamel-Reid博士和Igor Jurisica博士负责的研究小组收集了多伦多综合医院的多例口腔鳞状细胞癌和非口腔鳞状细胞癌患者的口腔组织样本，并进行了检测。
研究者们使用了meta分析的统计方法，综合了之前研究报道的五项基因芯片研究结果，并结合自己的研究结果，准确的找除了在口腔鳞状细胞癌组织中高表达的138种基因。并发现其中有四种基因与口腔鳞状细胞癌的复发率密切相关，它们分别是MMP1, COL4A1, P4HA2和THBS2。
研究者们说道：“我们的数据显示高表达MMP1, COL4A1, P4HA2和THBS2与高的口腔鳞状细胞癌复发率相关。这项研究将有助于未来临床口腔鳞状细胞癌的复发诊断。”(生物谷 Bioon.com)
doi:10.1186/1471-2407-11-437
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A gene signature in histologically normal surgical margins is predictive of oral carcinoma recurrence
Patricia P Reis , Levi Waldron , Bayardo Perez-Ordonez , Melania Pintilie , Natalie Naranjo Galloni , Yali Xuan , Nilva K Cervigne , Giles C Warner , Antti A Makitie , Colleen Simpson , David Goldstein , Dale Brown , Ralph Gilbert , Patrick Gullane , Jonathan Irish , Igor Jurisica and Suzanne Kamel-Reid
Background
Oral Squamous Cell Carcinoma (OSCC) is a major cause of cancer death worldwide, which is mainly due to recurrence leading to treatment failure and patient death. Histological status of surgical margins is a currently available assessment for recurrence risk in OSCC; however histological status does not predict recurrence, even in patients with histologically negative margins. Therefore, molecular analysis of histologically normal resection margins and the corresponding OSCC may aid in identifying a gene signature predictive of recurrence.
Methods
We used a meta-analysis of 199 samples (OSCCs and normal oral tissues) from five public microarray datasets, in addition to our microarray analysis of 96 OSCCs and histologically normal margins from 24 patients, to train a gene signature for recurrence. Validation was performed by quantitative real-time PCR using 136 samples from an independent cohort of 30 patients.
Results
We identified 138 significantly over-expressed genes (>2-fold, false discovery rate of 0.01) in OSCC. By penalized likelihood Cox regression, we identified a 4-gene signature with prognostic value for recurrence in our training set. This signature comprised the invasion-related genes MMP1, COL4A1, P4HA2, and THBS2. Over-expression of this 4-gene signature in histologically normal margins was associated with recurrence in our training cohort (p=0.0003, logrank test) and in our independent validation cohort (p=0.04, HR=6.8, logrank test).
Conclusion
Gene expression alterations occur in histologically normal margins in OSCC. Over-expression of the 4-gene signature in histologically normal surgical margins was validated and highly predictive of recurrence in an independent patient cohort. Our findings may be applied to develop a molecular test, which would be clinically useful to help predict which patients are at a higher risk of local recurrence.
