Expression of the significance of silent information regulator type-1 in Angioimmunoblastic T-cell lymphoma is greater association with tumorigenesis and has strong implications for adverse prognosis

Cell Cycle. 2016 Jun 17;15(12):1545-51. doi: 10.1080/15384101.2016.1172157. Epub 2016 Apr 28.

Abstract

Silent information regulator type-1 (SIRT1) is the best-studied member of the Sirtuin (Sir2) family of nicotinamide dinucleotide (NAD)-dependent class III histone deacetylases (HDACs). Rrecently, it is suggested that SIRT1 may be involved in the development of malignant tumors including mouse lymphoma, but has not yet been explored in Angioimmunoblastic T-cell lymphoma (AITL). Therefore, we investigated the prevalence and the prognostic impact of SIRT1 expression in AITL. Immunohistochemical expression of SIRT1, p53 were evaluated by using a 2 mm core from 45 AITL patients. Positive expression of SIRT1 was seen in 71.11% (32 of 45) of patients and p53 expression were seen in 53.33% (24 of 45). SIRT1 and p53 expression were significantly associated with shorter PFS by univariate analysis (P=0.009 and P < 0.001, respectively), multivariate analysis also shows that SIRT1 expression relate to worse prognosis. We also suggest inferior survival in AITL with the combined expression of SIRT1 and clinical characteristics of high IPI scores, high clinical stage, increased serum LDH, decreased HGB and increased γ-Globulin. In conclusion, our results indicate that SIRT1 is strongly expressed in AITL and it act as a clinically significant prognostic indicator for AITL patients, may also serve as a therapeutic target in AITL.

Keywords: AITL; SIRT1; prognosis; tumor; tumorigenesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Carcinogenesis / genetics*
  • Carcinogenesis / metabolism
  • Carcinogenesis / pathology
  • Cyclophosphamide / therapeutic use
  • Doxorubicin / therapeutic use
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Immunoblastic Lymphadenopathy / diagnosis
  • Immunoblastic Lymphadenopathy / drug therapy
  • Immunoblastic Lymphadenopathy / genetics*
  • Immunoblastic Lymphadenopathy / mortality
  • L-Lactate Dehydrogenase / blood
  • L-Lactate Dehydrogenase / genetics
  • Lymphoma, T-Cell, Peripheral / diagnosis
  • Lymphoma, T-Cell, Peripheral / drug therapy
  • Lymphoma, T-Cell, Peripheral / genetics*
  • Lymphoma, T-Cell, Peripheral / mortality
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Neoplasm Staging
  • Prednisone / therapeutic use
  • Prognosis
  • Sirtuin 1 / genetics*
  • Sirtuin 1 / metabolism
  • Survival Analysis
  • Tumor Suppressor Protein p53 / genetics
  • Tumor Suppressor Protein p53 / metabolism
  • Vincristine / therapeutic use
  • gamma-Globulins / genetics
  • gamma-Globulins / metabolism

Substances

  • Tumor Suppressor Protein p53
  • gamma-Globulins
  • Vincristine
  • Doxorubicin
  • Cyclophosphamide
  • L-Lactate Dehydrogenase
  • SIRT1 protein, human
  • Sirtuin 1
  • Prednisone

Supplementary concepts

  • CHOP protocol