Hibi K, Liu Q, Beaudry G A, Madden S L, Westra W H, Wehage S L, Yang S C, Heitmiller R F, Bertelsen A H, Sidransky D, Jen J
Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205-2196, USA.
Cancer Res. 1998 Dec 15;58(24):5690-4.
We used the serial analysis of gene expression (SAGE) method to systematically analyze transcripts present in non-small cell lung cancer. Over 226,000 SAGE tags were sequence analyzed from two independent primary lung cancers and two normal human bronchial/tracheal epithelial cell cultures. A total of 226,000 SAGE tags were sequence identified, representing 43,254 unique transcripts. Comparison of the tags present in the tumor with those identified in the normal tissue revealed 175 transcript tags that were overrepresented in the normal tissue and 142 tags that were overexpressed in the tumor by 10-fold or more. Northern hybridization was performed on 15 of the most abundantly expressed tags identified in the tumors. These tags were derived from either a known gene or a matched expressed sequence tag clone. The transcripts for 3 of the 15 genes, PGP 9.5, B-myb, and human mutT, were abundantly expressed in primary lung cancers (10 of 18, 15 of 18, and 6 of 12 tumors, respectively). In contrast, the presence of PGP9.5 and B-myb was much less frequent in primary tumors derived from other tissue origins. These results suggest that at least a portion of the transcripts identified by SAGE are frequently associated with lung cancer, and that their overexpression may contribute to lung tumorigenesis. The identification and further characterization of genes generated by SAGE should provide potential new targets for the diagnosis, prognosis, and therapy of lung cancer.
我们使用基因表达序列分析(SAGE)方法系统地分析非小细胞肺癌中存在的转录本。从两个独立的原发性肺癌和两个人类正常支气管/气管上皮细胞培养物中对超过226,000个SAGE标签进行了序列分析。总共鉴定出226,000个SAGE标签序列,代表43,254个独特的转录本。将肿瘤中存在的标签与正常组织中鉴定出的标签进行比较,发现175个转录本标签在正常组织中过度表达,142个标签在肿瘤中过表达10倍或更多。对肿瘤中鉴定出的15个表达最丰富的标签进行了Northern杂交。这些标签来自已知基因或匹配的表达序列标签克隆。15个基因中的3个,即PGP 9.5、B-myb和人类mutT的转录本在原发性肺癌中大量表达(分别在18个肿瘤中的10个、18个肿瘤中的15个和12个肿瘤中的6个中表达)。相比之下,PGP9.5和B-myb在源自其他组织来源的原发性肿瘤中的出现频率要低得多。这些结果表明,至少一部分通过SAGE鉴定出的转录本经常与肺癌相关,并且它们的过表达可能有助于肺癌的发生。通过SAGE鉴定和进一步表征的基因应为肺癌的诊断、预后和治疗提供潜在的新靶点。