Prognostic significance of miR-34a and its target proteins of FOXP1, p53, and BCL2 in gastric MALT lymphoma and DLBCL.
BACKGROUND
Mucosa-associated lymphoid tissue (MALT) lymphoma and diffuse large B-cell lymphoma (DLBCL), which are the two most common types of gastric lymphomas, have different clinicopathological features and molecular characteristics with distinct clinical outcomes. Tumor suppressor miR-34a connects the p53 network with forkhead box protein 1 (FOXP1) and BCL2. Here, we investigated the prognostic value of these molecules in gastric MALT lymphoma and DLBCL for use in routine clinical practice.


METHODS
Relative miR-34a expression was detected by quantitative reverse transcriptase-polymerase chain reaction in 20 cases of MALT lymphomas and 20 cases of DLBCLs. Tissue microarray, in situ hybridization, and immunohistochemistry analysis were used to examine the expression of miR-34a and its regulated genes, FOXP1, p53, and BCL2 proteins, in 64 patients with gastric MALT lymphoma and in 58 patients with DLBCL. Helicobacter pylori infection, overall survival (OS), and progression-free survival (PFS) were documented.


RESULTS
The expression level of miR-34a was markedly decreased in MALT lymphomas and DLBCLs compared to normal gastric tissues and peripheral blood mononuclear cells. miR-34a was present in the cytoplasm and nucleus of lymphocytes. Its expression was significantly downregulated in MALT and DLBCL lymphoma tissues, as compared with normal lymphocytes. The expression level of miR-34a in DLBCL was lower than in MALT lymphoma. FOXP1 was found to be positive in 48%, p53 in 20%, and BCL2 in 68% of MALT lymphoma cases. The corresponding positive rates of these markers in DLBCL were 64, 57, and 52%, respectively. High expression of FOXP1, p53, and BCL2 was seen in stage III and IV of both types of lymphomas. FOXP1, p53, and BCL2 positivity was associated with poor OS with both lymphoma types but OS with DLBCL was significantly lower than with MALT lymphoma.


CONCLUSIONS
Decreased miR-34a expression and increased FOXP1, p53, and BCL2 coexpression to predict a poor OS for MALT lymphoma and DLBCL patients could become very important prognostic markers in daily clinical work. Further investigation of these changes may be of prognostic significance in clinical practice.
Department of Pathology, Changhai Hospital, The Second Military Medical University, 168 Changhai Rd., Shanghai, 200433, China.
Miaoxia
M
He
Li
L
Gao
Shimin
S
Zhang
Liyang
L
Tao
Jianjun
J
Wang
Jianmin
J
Yang
Minghua
M
Zhu
D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D051858:Forkhead Transcription Factors / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D016481:Helicobacter Infections / Q000150:complications; D016480:Helicobacter pylori / Q000302:isolation & purification; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000166:cytology; D018442:Lymphoma, B-Cell, Marginal Zone / Q000235:genetics / Q000473:pathology*; D016403:Lymphoma, Large B-Cell, Diffuse / Q000235:genetics / Q000473:pathology*; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics; D012097:Repressor Proteins / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013534:Survival; D046888:Tissue Array Analysis; D016159:Tumor Suppressor Protein p53 / Q000235:genetics
C486626:FOXP1 protein, human; D051858:Forkhead Transcription Factors; C522425:MIRN34 microRNA, human; D035683:MicroRNAs; D019253:Proto-Oncogene Proteins c-bcl-2; D012097:Repressor Proteins; D016159:Tumor Suppressor Protein p53