Deregulated expression of Nucleophosmin 1 in gastric cancer and its clinicopathological implications

BMC Gastroenterology

Research Article

Margarita Cortes Martinez¹  Roger Chammas¹  Tatianee Katsue Furuya Mazzotti¹  Priscilae Daniele Ramos Cirilo¹  Marília Cardoso Smith²  Mariana Ferreira Leal³  Danielle Queiroz Calcagno⁴  Rommel Rodríguez Burbano⁵  Samia Demachki⁶  Paulo Pimentel Assumpção⁶ 

[1] Experimental Oncology Laboratory, Department of Radiology, School of Medicine, University of São Paulo, 01246-903, São Paulo, SP, Brazil;Center for Translational Oncology, São Paulo State Cancer Institute, 01246-000, São Paulo, SP, Brazil;Genetics Division, Department of Morphology and Genetic, Federal University of São Paulo, R. Botucatu, 740, CEP 04023-900, São Paulo, SP, Brazil;Genetics Division, Department of Morphology and Genetic, Federal University of São Paulo, R. Botucatu, 740, CEP 04023-900, São Paulo, SP, Brazil;Department of Orthopedics and Traumatology, Federal University of São Paulo, 04038-031, São Paulo, SP, Brazil;Genetics Division, Department of Morphology and Genetic, Federal University of São Paulo, R. Botucatu, 740, CEP 04023-900, São Paulo, SP, Brazil;Research Center of Oncology, João de Barros Barreto University Hospital, Federal University of Pará, 60673-000, Belém, PA, Brazil;Human Cytogenetics Laboratory, Institute of Biological Sciences, Federal University of Pará, 66073-000, Belém, PA, Brazil;Research Center of Oncology, João de Barros Barreto University Hospital, Federal University of Pará, 60673-000, Belém, PA, Brazil;

关键词: Gastric cancer;    Nucleophosmin;    Gene expression;    Protein expression;   

DOI  :  10.1186/1471-230X-14-9

 received in 2013-03-05, accepted in 2013-12-31,  发布年份 2014

来源: Springer

【 摘 要 】

BackgroundThe process of gastric carcinogenesis still remains to be elucidated. The identification of genes related to this process may help to reduce mortality rates through early diagnosis and the development of new anticancer therapies. Nucleophosmin 1 (NPM1) acts in ribosome biogenesis, centrosome duplication, maintenance of genomic stability, and embryonic development. Recently, NPM1 has been implicated in the tumorigenesis processes. Here, we evaluated NPM1 gene and protein expression in gastric tumors and in corresponding non-neoplastic gastric samples.MethodsNPM1 protein expression was determined by Western blot in 17 pairs of gastric tumors and corresponding non-neoplastic gastric tissue. The protein immunoreactivity was observed in 12 tumor samples. mRNA expression was evaluated by reverse transcription quantitative polymerase chain reaction (RT-qPCR) in 22 pairs of gastric tumors and in matched non-neoplastic gastric tissue.ResultsNPM1 protein expression was significantly reduced in gastric cancer samples compared to matched non-neoplastic gastric samples (P = 0.019). The protein level of NPM1 was reduced at least 1.5-fold in 35% of tumors compared to paired non-neoplastic gastric tissue. However, NPM1 immunoreactivity was detected in neoplastic and non-neoplastic cells, including in intestinal metaplastic, gastritis and inflammatory cells. NPM1 was mainly expressed in nucleus and nucleolus subcellular compartments. The staining intensity and the percentage of immunoreactive cells varied among the studied cases. The NPM1 mRNA level was reduced at least 1.5-fold in 45.5% of samples and increased in 27.3% of samples. An inverse correlation between protein and mRNA expression was detected (r = -0.509, P = 0.037). Intestinal-type gastric cancer presented higher mRNA levels than diffuse-type (P = 0.026). However, reduced NPM1 protein expression was associated with intestinal-type gastric cancer compared to matched non-neoplastic gastric samples (P = 0.018). In addition, tumors from patients with known distant metastasis presented reduced NPM1 protein levels compared to tumors from patients without distant metastasis (P < 0.001).ConclusionAlthough the expression of NPM1 is heterogeneous in gastric tumors, our results suggest that NPM1 down-regulation may have a role in gastric carcinogenesis and may help in the selection of anticancer treatment strategies.

【 授权许可】

CC BY   
© Leal et al.; licensee BioMed Central Ltd. 2014