Τίτλος:
Variant of BCL3 gene is strongly associated with five-year survival of non-small-cell lung cancer patients
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
Objectives: BCL3, a known atypical IκB family member, has been documented to be upregulated in hematological malignancies and in some solid tumors, functioning as a crucial player in tumor development. Recently, rs8100239, a tag-Single Nucleotide Polymorphism (SNP) in BCL3 (T > A) has been identified, but there are no data regarding its involvement in non-small-cell lung cancer (NSCLC) initiation and progression. Materials and methods: To study the possible association of BCL3 with NSCLC, 268 patients and 279 healthy controls were genotyped for rs8100239. Moreover, BCL3 protein expression was also investigated in 112 NSCLC cases through an immunohistochemical analysis. Results: NSCLC patients with AA genotype displayed significantly worse prognosis compared to T allele carriers (P < 0.001), who had less frequent intermediate nuclear BCL3 expression (P = 0.042). In addition, overexpression of BCL3 was detected in tumor specimens, compared to normal tissue (P < 0.001). Furthermore, BCL3 protein levels were associated with five-year survival (P=0.039), maximum diameter of lesion (P = 0.012), grade (P = 0.002) and relapse frequency (P = 0.041). Conclusions: The present study is the first to show a relationship between the genetic variation rs8100239 of BCL3 and cancer patients' survival. It also represents the first quantitative evaluation of BCL3 expression in NSCLC. Our findings indicate that rs8100239 may be considered as a novel prognostic indicator, demonstrating also the overexpression of BCL3 protein in NSCLC and implicating this pivotal molecule in the pathogenesis of NSCLC. © 2015 Elsevier Ireland Ltd.
Συγγραφείς:
Dimitrakopoulos, F.-I.D.
Antonacopoulou, A.G.
Kottorou, A.
Marousi, S.
Koukourikou, I.
Kalofonou, M.
Panagopoulos, N.
Scopa, C.
Dougenis, D.
Papadaki, H.
Papavassiliou, A.G.
Kalofonos, H.P.
Εκδότης:
Elsevier Ireland Ltd
Λέξεις-κλειδιά:
protein bcl 3; oncoprotein; proto-oncogene protein bcl-3; transcription factor, adult; aged; Article; cancer grading; cancer prognosis; cancer recurrence; controlled study; female; genetic association; genetic variability; human; human tissue; immunohistochemistry; major clinical study; male; non small cell lung cancer; priority journal; protein expression; single nucleotide polymorphism; survival rate; allele; cancer staging; case control study; gene expression; gene frequency; genetics; genotype; lung tumor; lymph node metastasis; metabolism; middle aged; mortality; non small cell lung cancer; pathology; prognosis; survival analysis; tumor recurrence; tumor volume; very elderly, Adult; Aged; Aged, 80 and over; Alleles; Carcinoma, Non-Small-Cell Lung; Case-Control Studies; Female; Gene Expression; Gene Frequency; Genotype; Humans; Lung Neoplasms; Lymphatic Metastasis; Male; Middle Aged; Neoplasm Grading; Neoplasm Recurrence, Local; Neoplasm Staging; Polymorphism, Single Nucleotide; Prognosis; Proto-Oncogene Proteins; Survival Analysis; Transcription Factors; Tumor Burden
DOI:
10.1016/j.lungcan.2015.06.006
