Identification and validation of genes involved in gastric tumorigenesis.
Identification and validation of genes involved in gastric tumorigenesis.
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DOI：
10.1186/1475-2867-10-45
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发表时间：
2010-11-24
影响因子：
5.8
通讯作者：
Ramakrishnan SA
中科院分区：
文献类型：
--
作者：
Rajkumar T;Vijayalakshmi N;Gopal G;Sabitha K;Shirley S;Raja UM;Ramakrishnan SA
胃癌是印度南部常见的癌症之一。不幸的是，90%以上的人在向该国的第三中心报到时已经提前了。迫切需要对这些癌症进行表征，并尝试识别潜在的生物标志物和新的治疗靶点。我们使用24例胃癌、20例配对正常（PN）和5例从非胃癌患者获得的明显正常胃组织（明显正常- AN）进行微阵列研究，然后使用Taqman低密度阵列真实的时间PCR通过相对定量验证显著基因（n = 63）。然后，我们使用定制的Quantibody蛋白阵列来验证15种蛋白在胃组织（4种AN，9种PN和9种胃癌）中的表达。使用相同的阵列格式来研究58名胃癌患者和18名正常/非恶性胃病患者的这些蛋白质的血浆水平。首次发现17个基因（ASPN、CCL 15/MIP-1δ、MMP 3、SPON 2、PRSS 2、CCL 3、TMEPAI/PMEPAI、SIX 3、MFNG、SOSTDC 1、SGNE 1、SST、IGHA 1、AKR 1B 10、FCGBP、ATP 4 B、NCAPH 2）在肿瘤与配对正常之间存在差异表达。肿瘤与AN和PN之间的EpCAM（p = 0.0001）、IL 8（p = 0.0003）、CCL 4/MIP-1β（p = 0.0026）、CCL 20/MIP-3α（p = 0.039）和TIMP 1（p = 0.0017）组织蛋白水平显著不同（Mann Whitney U检验）。IL 8、CXCL 9/MIP-1α、CCL 3/MIP-1α、CCL 20/MIP-3α、PDGFR-B和TIMP-1蛋白的中位血浆水平在非恶性组和胃癌组之间差异有统计学意义。术后EpCAM、IGFBP 3、IL 8、CXCL 10/IP 10、CXCL 9/IP 10、CCL 3/MIP-1α、CCL 20/MIP-3α、SPP 1/OPN和PDGFR-B水平在所有研究的样本中均显示出均匀的下降。我们的研究已经确定了几个在胃癌中差异表达的基因，有些是第一次。其中一些在蛋白质水平上也得到了证实。这些蛋白质中的一些将需要进一步评估其作为胃癌诊断生物标志物的潜力，一些可能是有用的作为胃癌的后续标志物。
Gastric cancer is one of the common cancers seen in south India. Unfortunately more than 90% are advanced by the time they report to a tertiary centre in the country. There is an urgent need to characterize these cancers and try to identify potential biomarkers and novel therapeutic targets. We used 24 gastric cancers, 20 Paired normal (PN) and 5 apparently normal gastric tissues obtained from patients with non-gastric cancers (Apparently normal - AN) for the microarray study followed by validation of the significant genes (n = 63) by relative quantitation using Taqman Low Density Array Real Time PCR. We then used a custom made Quantibody protein array to validate the expression of 15 proteins in gastric tissues (4 AN, 9 PN and 9 gastric cancers). The same array format was used to study the plasma levels of these proteins in 58 patients with gastric cancers and 18 from patients with normal/non-malignant gastric conditions. Seventeen genes (ASPN, CCL15/MIP-1δ, MMP3, SPON2, PRSS2, CCL3, TMEPAI/PMEPAI, SIX3, MFNG, SOSTDC1, SGNE1, SST, IGHA1, AKR1B10, FCGBP, ATP4B, NCAPH2) were shown to be differentially expressed between the tumours and the paired normal, for the first time. EpCAM (p = 0.0001), IL8 (p = 0.0003), CCL4/MIP-1β (p = 0.0026), CCL20/MIP-3α (p = 0.039) and TIMP1 (p = 0.0017) tissue protein levels were significantly different (Mann Whitney U test) between tumours versus AN & PN. In addition, median plasma levels of IL8, CXCL9/MIG, CCL3/MIP-1α, CCL20/MIP-3α, PDGFR-B and TIMP1 proteins were significantly different between the non-malignant group and the gastric cancer group. The post-surgical levels of EpCAM, IGFBP3, IL8, CXCL10/IP10, CXCL9/MIG, CCL3/MIP-1α, CCL20/MIP-3α, SPP1/OPN and PDGFR-B showed a uniform drop in all the samples studied. Our study has identified several genes differentially expressed in gastric cancers, some for the first time. Some of these have been confirmed at the protein level, as well. Some of these proteins will need to be evaluated further for their potential as diagnostic biomarkers in gastric cancers and some could be useful as follow-up markers in gastric cancer.
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影响因子：
6.4
作者：
Matsuo, Yoichi;Ochi, Nobuo;Sawai, Hirozumi;Yasuda, Akira;Takahashi, Hiroki;Fumahashi, Hitoshi;Takeyama, Hiromitsu;Tong, Zhimin;Guha, Sushovan
通讯作者：
Guha, Sushovan
影响因子：
1.4
作者：
Gigek, Carolina Oliveira;Leal, Mariana Ferreira;Cardoso Smith, Marilia de Arruda
通讯作者：
Cardoso Smith, Marilia de Arruda
影响因子：
6.8
作者：
Mroczko, Barbara;Groblewska, Magdalena;Szmitkowski, Maciej
通讯作者：
Szmitkowski, Maciej
影响因子：
8.5
作者：
Kuniyasu, H.;Oue, N.;Yasui, W.
通讯作者：
Yasui, W.
影响因子：
3.4
作者：
Galamb, Orsolya;Sipos, Ferenc;Tulassay, Zsolt
通讯作者：
Tulassay, Zsolt