期刊论文详细信息
BMC Gastroenterology
Gene expression profiling of laterally spreading tumors
Osamu Yokosuka1  Takashi Kishimoto2  Tatsuro Katsuno1  Tomoo Nakagawa1  Tomoaki Matsumura1  Daisuke Maruoka1  Keiko Saito1  Arata Oyamada1  Kenichiro Okimoto1  Makoto Arai1  Takeshi Tanaka1  Shoko Minemura1 
[1] Department of Gastroenterology and Nephrology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chiba 260-8670, Japan;Department of Molecular Pathology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chiba 260-8670, Japan
关键词: BCL2L1;    Array analysis;    Gene expression;    Colon;    Laterally spreading tumor;   
Others  :  1224304
DOI  :  10.1186/s12876-015-0295-1
 received in 2015-01-12, accepted in 2015-05-27,  发布年份 2015
PDF
【 摘 要 】

Background

Laterally spreading tumors (LSTs) are generally defined as lesions >10 mm in diameter, are characterized by lateral expansion along the luminal wall with a low vertical axis. In contrast to other forms of tumor, LSTs are generally considered to have a superficial growth pattern and the potential for malignancy. We focused on this morphological character of LSTs, and analyzed the gene expression profile of LSTs.

Methods

The expression of 168 genes in 41 colorectal tumor samples (17 LST-adenoma, 12 LST-carcinoma, 12 Ip [pedunculated type of the Paris classification)-adenoma, all of which were 10 mm or more in diameter] was analyzed by PCR array. Based on the results, we investigated the expression levels of genes up-regulated in LST-adenoma, compared to Ip-adenoma, by hierarchical and K-means clustering. To confirm the results of the array analysis, using an additional 60 samples (38 LST-adenoma, 22 Ip-adenoma), we determined the localization of the gene product by immunohistochemical staining.

Result

The expression of 129 genes differed in colorectal tumors from normal mucosa by PCR array analysis. As a result of K-means clustering, the expression levels of five genes, AKT1, BCL2L1, ERBB2, MTA2 and TNFRSF25, were found to be significantly up-regulated (p < 0.05) in LST-adenoma, compared to Ip-adenoma. Immunohistochemical analysis showed that the BCL2L1 protein was significantly and meaningfully up-regulated in LST-adenoma compared to Ip-adenoma (p = 0.010). With respect to apoptosis status in LST-Adenoma, it assumes that BCL2L1 is anti-apoptotic protein, the samples such as BCL2L1 positive and TUNEL negative, or BCL2L1 negative and TUNEL positive are consistent with the assumption. 63.2 % LST-adenoma samples were consistent with the assumption.

Conclusions

LSTs have an unusual profile of gene expression compared to other tumors and BCL2L1 might be concerned in the organization of LSTs.

【 授权许可】

   
2015 Minemura et al.; licensee BioMed Central.

【 预 览 】
附件列表
Files Size Format View
20150909065915619.pdf 1261KB PDF download
Fig. 3. 89KB Image download
Fig. 2. 16KB Image download
Fig. 1. 130KB Image download
【 图 表 】

Fig. 1.

Fig. 2.

Fig. 3.

【 参考文献 】
  • [1]Kudo S: Endoscopic mucosal resection of flat and depressed types of early colorectal cancer. Endoscopy 1993, 25:455-61.
  • [2]Hurlstone DP, Sanders DS, Cross SS, Adam I, Shorthouse AJ, Brown S, et al.: Colonoscopic resection of lateral spreading tumours: a prospective analysis of endoscopic mucosal resection. Gut 2004, 53:1334-9.
  • [3]Kudo S, Kashida H, Nakajima T, Tamura S, Nakajo K: Endoscopic diagnosis and treatment of early colorectal cancer. World J Surg 1997, 21:694-701.
  • [4]Sakashita M, Aoyama N, Maekawa S, et al.: Flat-elevated and depressed, subtypes of flat early colorectal cancers, should be distinguished by their pathological features. Int J Colorectal Dis 2000, 15:275-81.
  • [5]Saitoh Y, Waxman I, West AB, et al.: Prevalence and distinctive biologic features of flat colorectal adenomas in a North American population. Gastroenterology 2001, 120:1657-65.
  • [6]Soetikno RM, Kaltenbach T, Rouse RV, et al.: Prevalence of nonpolypoid (flat and depressed) colorectal neoplasms in asymptomatic and symptomatic adults. JAMA 2008, 299:1027-35.
  • [7]Kudo S, Lambert R, Allen JI, et al.: Nonpolypoid neoplastic lesions of the colorectal mucosa. Gastrointest Endosc 2008, 68:S3-47.
  • [8]Kyokane K, Ito M, Sato Y, et al.: Expression of bcl-2 and p53 correlates with the morphology of gastric neoplasia. J Pathol 1998, 184:382-9.
  • [9]Kim WH, Suh JH, Kim TI, et al.: Colorectal flat neoplasia. Dig Liver Dis 2003, 35:165-71.
  • [10]Abe S, Terai T, Sakamoto N, et al.: Clinicopathological features of non-polypoid colorectal tumors as viewed from the patients’ background. J Gastroenterol 2006, 41:325-31.
  • [11]Mueller JD, Bethke B, Stolte M: Colorectal de novo carcinoma: a review of its diagnosis, histopathology, molecular biology, and clinical relevance. Virchows Arch 2002, 440:453-60.
  • [12]Takahashi T, Nosho K, Yamamoto H, et al.: Flattype colorectal advanced adenomas (laterally spreading tumors) have different genetic and epigenetic alterations from protruded-type advanced adenomas. Mod Pathol 2007, 20:139-47.
  • [13]Nosho K, Yamamoto H, Mikami M, et al.: Laterally spreading tumour in which interstitial deletion of beta-catenin exon 3 was detected. Gut 2005, 54:1504-5.
  • [14]Hashimoto S, Higaki S, Amano A, et al.: Relationship between molecular markers and endoscopic findings in laterally spreading tumors. J Gastroenterol Hepatol 2007, 22:30-6.
  • [15]Sugimoto T, Ohta M, Ikenoue T, et al.: Macroscopic morphologic subtypes of laterally spreading colorectal tumors showing distinct molecular alterations. Int J Cancer 2010, 127:1562-9.
  • [16]Sada M, Mitomi H, Igarashi M, et al.: Cell kinetics, p53 and bcl-2 expression, and c-Ki-ras mutations in flat-elevated tubulovillous adenomas and adenocarcinomas of the colorectum: comparison with polypoid lesions. Scand J Gastroenterol 1999, 34:798-807.
  • [17]Noro A, Sugai T, Habano W, Nakamura S: Analysis of Kiras and p53 gene mutations in laterally spreading tumors of the colorectum. Pathol Int 2003, 53:828-36.
  • [18]Mukawa K, Fujii S, Takeda J, et al.: Analysis of K-ras mutations and expression of cyclooxygenase-2 and gastrin protein in laterally spreading tumors. J Gastroenterol Hepatol 2005, 20:1584-90.
  • [19]Hiraoka S, Kato J, Tatsukawa M, Hrada K, Fujita H, Morikawa T, et al.: Laterally spreading type of colorectal adenoma exhibits a unique methylation phenotype and K-ras mutations. Gastroenterology 2006, 131:379-89.
  • [20]Kaji E, Kato J, Suzuki Hkita M, Horii J, Saito S, et al.: Analysis of K-ras, BRAF, and PIK3CA mutations in laterally-spreading tumors of the colorectum. J Gastroenterol Hepatol 2011, 26:599-607.
  • [21]Higaki S, Hashimoto S, Harada K, Nohara H, Saito Y, Gondo T, et al.: Long-term follow-up of large flat colorectal tumors resected endoscopically. Endoscopy 2003, 35:845-9.
  • [22]Craig RW: The bcl-2 gene family. Semin Cancer Biol 1995, 6:35-43.
  • [23]Hockenbery D, Nunez G, Milliman C, Schreiber RD, Korsmeyer SJ: Bcl-2 is an inner mitochondrial membrane protein that blocks programmed cell death. Nature 1990, 348:334-6.
  • [24]Williams GT: Programmed cell death: apoptosis and oncogenesis. Cell 1991, 65:1097-8.
  • [25]Johnston PG, O’Brien MJ, Dervan PA: Immunohistochemical analysis of cell kinetic parameters in colonic adenocarcinomas, adenomas, and normal mucosa. Hum Pathol 1989, 20:696-700.
  • [26]Koike M: Significance of spontaneous apoptosis during colorectal tumorigenesis. J Surg Oncol 1996, 62:97-108.
  • [27]Krajewska M, Moss SF, Krajewski S, et al.: Elevated expression of Bcl-X and reduced Bak in primary colorectal adenocarcinomas. Cancer Res 1996, 56:2422-7.
  • [28]Kikuchi Y, Dinjens WN, Bosman FT: Proliferation and apoptosis in proliferative leseions of colon and rectum. Virchows Arch 1997, 431:111-7.
  • [29]de Sousa-Júnior EC, Alencar AP, da Silva BB: Ki-67 and Bcl-2 antigen expression in adenomatous colorectal polyps from women with breast cancer. Ann Surg Oncol 2010, 17(9):2378-83.
  • [30]Suzuki Y, Honma T, Hayashi S, et al.: Bcl-2 expression and frequency of apoptosis correlate with morphogenesis of colorectal neoplasia. J Clin Pathol 2002, 55:212-7.
  • [31]Yamada H, Hasegawa H, Iino H, et al.: Evaluation of apoptosis as a factor affecting the growth of non-polypoid colorectal adenomas. J Int Med Res 2001, 29:516-22.
  文献评价指标  
  下载次数:36次 浏览次数:15次