Overexpression of DNA methyltransferase 1 as a negative independent prognostic factor in primary gastrointestinal diffuse large B-cell lymphoma treated with CHOP-like regimen and rituximab

Abstract

Abstract. The aims of the present study were to elucidate the transcript levels of DNA methyltransferase (DNMT)1, DNMT3a and DNMT3b by quantitative polymerase chain reaction in patients with primary gastrointestinal diffuse large B-cell lymphoma (PGI-DLBCL), and determine the association of their expression with the clinical parameters and prognostic values of the disease. The results revealed that the expression of DNMT1 in patients with PGI-DLBCL was significantly higher than that in healthy controls (P=0.04), while the expression of DNMT3a and DNMT3b were significantly lower (P<0.001 and P=0.001, respectively). The increased expression of DNMT1 was significantly correlated with shorter overall survival and progression-free survival rates (P=0.018 and P=0.008, respectively). The multivariate analysis demonstrated that the level of DNMT1 was an independent prognostic factor. In conclusion, DNMT1 was identified to be an independent prognostic factor for predicting the survival of patients with PGI-DLBCL; this suggests that it could be used as a marker to indicate the prognosis of PGI-DLBCL.

Differential expression of the epigenetic methylation-related protein DNMT1 by breast cancer molecular subtype and stromal histology

“…We found an association between high tumor expression of DNMT1 and shorter OS, concordant with previous studies in which high expression of DNMT1 was associated with poor prognosis in malignant lymphoma [ 10 ], renal cell carcinoma [ 18 ], pancreatic cancer [ 19 ], and bladder cancer [ 20 ]. The clinical significance of this result is the possibility of therapy targeting epigenetic methylation-related proteins such as DNMT1.…”

“…Immunohistochemical staining for 5-meC, DNMT1, and ISL1 was assessed semiquantitatively by light microscopy [ 10 ]. Staining results in malignant cells and stromal cells were assessed as 0, negative or weak immunostaining in <1 % of the tumor/stroma; 1, focal expression in 1–10 % of tumor/stroma; 2, positive in 11–50 % of tumor/stroma; and 3, positive in 51–100 % of tumor/stroma.…”

Expression of DNA methylation-related proteins in metastatic breast cancer

“…Tumoral DNMT1 expression was associated with shorter OS in present study. This result agreed with previous data that high expression of DNMT1 was correlated with poor prognosis in breast cancer [27], malignant lymphoma [19], renal cell carcinoma [36], pancreatic cancer [37], bladder cancer [38]. MUC1-C oncoprotein could be the link between DNMT1 expression and poor prognosis.…”

“…Staining results in cancer cells and stromal cells were assessed as 0, negative or weak immunostaining in <1% of the tumor/ stroma; 1, focal expression in 1-10% of tumor/stroma; 2, positive in 11-50% of tumor/stroma; and 3, positive in 51-100% of tumor/stroma. This evaluation was applied to all areas of the tumor in all samples; grade 0, 1 were negative and grades 2, 3 were positive [19]. Ki-67 labeling indices (LI) were scored by counting the number of positively stained nuclei and expressed as a percentage of total tumor cells.…”

The Lymphocyte–Monocyte Ratio and the Platelet–Lymphocyte Ratio at Diagnosis as Independent Prognostic Factors in Primary Gastrointestinal Diffuse Large B Cell Lymphoma

“…Endoscopic examination combined with pathological biopsy is still the most important and reliable method for detection of PGI-DLBCL. Nowadays, there is still no consensus on its treatment, the majority of patients were treated with combined therapy (chemotherapy and radiotherapy, surgery plus chemotherapy, surgery plus chemotherapy, and radiotherapy).The majority of chemotherapeutic protocols was CHOP (cyclophosphamide, doxorubicin, vincristine, prednisolone)-like regimens and/without rituximab [4][5][6]. Immunodeficiency is considered to be one of the most dangerous factors in NHL, with a greater risk of developing lymphoma with congenital or acquired immunodeficiency.…”