口腔鱗狀細(xì)胞癌發(fā)病率在所有頸部和頭部癌癥患者總?cè)藬?shù)中大約占有1/4的比例。它是癌癥引起死亡的主要因素—主要是由于目前沒有有效的組織檢查方法預(yù)測(cè)癌癥是否會(huì)復(fù)發(fā),。
在最新一期的《BMC Cancer》雜志上，科學(xué)家們發(fā)現(xiàn)有四種基因的表達(dá)可以準(zhǔn)確的預(yù)測(cè)患者復(fù)發(fā)口腔鱗狀細(xì)胞癌的風(fēng)險(xiǎn),。[A gene signature in histologically normal surgical margins is predictive of oral carcinoma recurrence.BMC Cancer.11. October 2011]
來自加拿大安大略湖癌癥中心的，由Suzanne Kamel-Reid博士和Igor Jurisica博士負(fù)責(zé)的研究小組收集了多倫多綜合醫(yī)院的多例口腔鱗狀細(xì)胞癌和非口腔鱗狀細(xì)胞癌患者的口腔組織樣本,，并進(jìn)行了檢測(cè),。
研究者們使用了meta分析的統(tǒng)計(jì)方法，綜合了之前研究報(bào)道的五項(xiàng)基因芯片研究結(jié)果,，并結(jié)合自己的研究結(jié)果,，準(zhǔn)確的找除了在口腔鱗狀細(xì)胞癌組織中高表達(dá)的138種基因。并發(fā)現(xiàn)其中有四種基因與口腔鱗狀細(xì)胞癌的復(fù)發(fā)率密切相關(guān),，它們分別是MMP1, COL4A1, P4HA2和THBS2,。
研究者們說道：“我們的數(shù)據(jù)顯示高表達(dá)MMP1, COL4A1, P4HA2和THBS2與高的口腔鱗狀細(xì)胞癌復(fù)發(fā)率相關(guān)。這項(xiàng)研究將有助于未來臨床口腔鱗狀細(xì)胞癌的復(fù)發(fā)診斷,。”(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.
