Bartczak-Tomczyk Malwina, Sałagacka Aleksandra, Mirowski Marek, Balcerczak Ewa
Laboratory of Molecular Biology and Pharmacogenomics, Department of Pharmaceutical Biochemistry, Medical University of Lodz, Lodz 90-151, Poland.
Exp Ther Med. 2012 Feb;3(2):237-242. doi: 10.3892/etm.2011.378. Epub 2011 Nov 9.
Colorectal cancer (CRC) is one of the most frequent neoplasms and is responsible for the second highest mortality rate of all cancers in the more developed regions of the world. The molecular mechanisms of CRC are relatively well characterized and are correlated to the accumulation of genetic mutations and certain patterns of gene expression/over-expression. There are a number of possible molecular factors involved in CRC progression in the aforementioned pathways, which are as yet not well described. One of these factors appears to be the gene FJ 194940.1, previously termed P65. FJ 194940.1 consists of 6 exons and probably undergoes alternative splicing in malignant tissues. In this study, tissue samples from 102 patients with colon cancer were investigated to confirm alternative splicing and to correlate results obtained with clinicopathological parameters. A total of 18 splice variants, which arise from various combinations of 4 exons (II, III, IV and V) and exon-exon junctions between exons 1 and 2 (I/II); 2 and 3 (II/III); 3 and 4 (III/IV), as well as 4 and 5 (IV/V), were found. For statistical analysis the full length transcript was divided into parts A and B. Part A consisted of exons II and III, as well as I/II and II/III exon-exon junctions, whereas part B comprised exons IV and V, as well as III/IV and IV/V exon-exon junctions. The expression of part B of the FJ 194940.1 gene transcript is correlated with well-differentiated (G1) and moderately differentiated cases (G2). Lymphocytic tumor infiltration, a good prognostic factor in CRC, was significantly correlated to the presence of all elements in part A of the FJ 194940.1 gene transcript. Patients who had all elements in part A of the transcript survived for a shorter duration. Investigation of the FJ 194940.1 gene revealed that the gene had undergone alternative splicing. However, the role of its transcripts and potential proteins should be examined in detail.
结直肠癌（CRC）是最常见的肿瘤之一，在世界较发达地区，其死亡率在所有癌症中位居第二。CRC的分子机制已得到相对充分的研究，与基因突变的积累以及某些基因表达/过表达模式相关。在上述途径中，有许多可能参与CRC进展的分子因素，但目前对它们的描述还不够充分。其中一个因素似乎是基因FJ 194940.1，以前称为P65。FJ 194940.1由6个外显子组成，在恶性组织中可能发生可变剪接。在本研究中，对102例结肠癌患者的组织样本进行了研究，以确认可变剪接，并将所得结果与临床病理参数相关联。共发现了18种剪接变体，它们由4个外显子（II、III、IV和V）以及外显子1和2之间（I/II）、2和3之间（II/III）、3和4之间（III/IV）以及4和5之间（IV/V）的外显子-外显子连接的各种组合产生。为了进行统计分析，将全长转录本分为A和B两部分。A部分由外显子II和III以及I/II和II/III外显子-外显子连接组成，而B部分包括外显子IV和V以及III/IV和IV/V外显子-外显子连接。FJ 194940.1基因转录本B部分的表达与高分化（G1）和中分化病例（G2）相关。淋巴细胞肿瘤浸润是CRC的一个良好预后因素，与FJ 194940.1基因转录本A部分中所有元件的存在显著相关。转录本A部分具有所有元件的患者存活时间较短。对FJ 194940.1基因的研究表明该基因发生了可变剪接。然而，其转录本和潜在蛋白质的作用应进行详细研究。
