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Molecular profiling of genes in squamous cell lung carcinoma in Asian Indians

机译:亚洲印第安人鳞状细胞癌基因的分子谱分析

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Early metastasis and a poor five-year survival make lung cancer the leading cause of cancer related deaths worldwide. The clinical profile of lung cancer patients in India differs from the West as they present earlier, with squamous cell carcinoma being the commonest histological type. We compared gene expression profiles in primary lung squamous cell carcinoma (LSCC) and matched normal lung tissues in Asian Indians. Using suppression subtractive hybridization, two subtracted cDNA libraries containing differentially expressed genes in the tumors were constructed. Differential expression was confirmed by reverse Northern blot analysis. DNA of confirmed clones was sequenced and subjected to GenBank Blast searches. RNA expression levels were then analyzed by Northern blotting and validated by semiquantitative RT-PCR (in 10 cases of NSCLC). Seventeen differentially expressed gene cDNA fragments of LSCC were analyzed. The differentially expressed genes included those associated with cellular metabolism, cell-cycle, -structure, -adhesion, transcription, proliferation, apoptosis and signal transduction. The study provided first evidence that KLAA0767, a Death Inducing Protein, a novel p53 independent target of EM, and Geminin, an inhibitor of DNA replication are differentially expressed in LSCC. Identification of the differentially expressed genes in lung cancer in this study may serve as better molecular markers for early diagnosis and identifying novel intervention sites for anticancer therapy. (c) 2008 Elsevier Inc. All rights reserved.
机译:早期转移和较差的五年生存率使肺癌成为全球范围内与癌症相关的死亡的主要原因。在印度,肺癌患者的临床特征与西方国家有所不同,鳞状细胞癌是最常见的组织学类型。我们比较了亚洲印第安人原发性肺鳞状细胞癌(LSCC)和匹配的正常肺组织中的基因表达谱。使用抑制消减杂交,构建了两个消减的cDNA文库,这些文库包含了肿瘤中差异表达的基因。通过反向Northern印迹分析证实了差异表达。对确认的克隆的DNA进行测序,然后进行GenBank Blast搜索。然后通过RNA印迹分析RNA表达水平,并通过半定量RT-PCR验证(在10例NSCLC中)。分析了17个LSCC差异表达的基因cDNA片段。差异表达的基因包括与细胞代谢,细胞周期,-结构,-粘附,转录,增殖,凋亡和信号转导相关的基因。这项研究提供了第一个证据,即LSCC中的一种死亡诱导蛋白KLAA0767(一种新型的p53独立的EM靶标)和Geminin(一种DNA复制的抑制剂)在细胞中差异表达。在这项研究中,肺癌中差异表达基因的鉴定可作为更好的分子标记物,用于早期诊断和鉴定新的抗癌治疗干预部位。 (c)2008 Elsevier Inc.保留所有权利。

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