Variant of BCL3 gene is strongly associated with five-year survival of non-small-cell lung cancer patients

Dimitrakopoulos, Foteinos-Ioannis; Antonacopoulou, Anna G.; Κοττόρου, Αναστασία; Marousi, Stella; Koukourikou, I.; Kalofonou, Melpomeni; Παναγόπουλος, Νικόλαος; Scopa, Chrisoula D.; Dougenis, Dimitrios; Papadaki, Helen; Papavassiliou, Athanasios G.; Kalofonos, Haralabos P.

doi:10.1016/j.lungcan.2015.06.006

Cited by 14 publications

(20 citation statements)

References 41 publications

(54 reference statements)

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“…This is consistent with findings of previously studies reporting dysregulation of BCL3 expression in T/B cell leukemia [ 16 – 18 ], Hodgkin lymphoma [ 19 , 20 ], T/B cell lymphoma [ 21 , 22 ]. Apart from hematology malignancies, BCL3 has been shown to be participated in progression of diverse solid tumors, such as breast cancer [ 15 ], renal-cell carcinoma [ 13 ], non-small-cell lung cancer [ 12 ], cervical cancer [ 11 ], colorectal cancer [ 23 ]. Although dysregulation and oncogenetic roles of BCL3 in hematology malignancies are well established, the diagnostic and prognostic values of this gene are still to be evaluated.…”

Section: Discussionmentioning

confidence: 99%

“…In addition to the diagnostic value of BCL3 in cancers, prognostic value of BCL3 remains controversial in human cancers. Elevated expression of BCL3 acted as unfavorable prognostic indicator has been reported in chronic lymphocytic leukemia, non-Hodgkin’s lymphoma, colorectal cancer, breast cancer [ 14 , 20 , 23 , 15 , 12 ]. Additionally, subcellualar location of BCL3 also is related to prognosis.…”

Section: Discussionmentioning

confidence: 99%

“…Nevertheless, latter research has shown that BCL3 rearrangement is recurrent in other hematological malignancies, such as T cell lymphoma, Burlitt-like lymphoma, Hodgkin lymphoma [ 6 – 8 ]. Disregulation of BCL3 without chromosomal translocation has been found to participate in progression in a variety of solid tumors, from breast cancer, nasopharyngeal carcinoma and renal-cell carcinoma to lung cancer [ 9 – 12 ]. Moreover, abnormal expression of BCL3 was associated with prognosis in patients with CLL, breast cancer, clear-cell renal-cell carcinoma and non-small-cell lung cancer [ 12 – 15 ].…”

Section: Introductionmentioning

confidence: 99%

“…Disregulation of BCL3 without chromosomal translocation has been found to participate in progression in a variety of solid tumors, from breast cancer, nasopharyngeal carcinoma and renal-cell carcinoma to lung cancer [ 9 – 12 ]. Moreover, abnormal expression of BCL3 was associated with prognosis in patients with CLL, breast cancer, clear-cell renal-cell carcinoma and non-small-cell lung cancer [ 12 – 15 ]. Due to its overexpression in numerous types of tumors, as well as its extensive roles in promoting transformation in hematologic malignancies, BCL3 has been recognized as an oncogenic gene.…”

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

BCL3 Expression Is a Potential Prognostic and Predictive Biomarker in Acute Myeloid Leukemia of FAB Subtype M2

Niu

Yang

Chen

et al. 2018

Pathol. Oncol. Res.

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Although the implication of BCL3 has been disclosed in human chronic lymphocytic leukemia as well as other solid tumors, the diagnostic and prognostic of BCL3 expression in acute myeloid leukemia (AML) remains largely unclear. In this study, we isolated total RNA from bone marrow mononuclear cells collected from 101 de novo AML patients and 27 healthy donors. After reverse transcription, quantitative real-time PCR was performed to detect BCL3 expression level. BCL3 mRNA level was significantly down-regulated in BMMCs of AML patients compared with healthy controls ( P = 0.0015). BCL3 was showed a higher level in AML patients with poor-risk karyotypes than that of in patients with favorable/intermediate-risk karyotypes ( P = 0.014). ROC analysis demonstrated that BCL3 could effectively differentiate AML patients from normal controls. Among the French-American-British (FAB) subtypes, the frequency of low BCL3 expression in M2 subtypes is significantly higher than that of in the other subtypes M1/M4/M5/M6/M7 ( P = 0.006), and mildly lower in myelomonocytic/monocytic subtypes M4/M5 ( P = 0.064) than those in M1/M2/M6/M7 subtypes. Chromosome analysis revealed that BCL3 low patients had a remarkably higher frequency of t (8;21) abnormality ( P = 0.0047) and lower frequency of normal karyotype ( P = 0.0059) than BCL3 high patients. BCL3 high patients showed a significantly higher frequency of FLT3-ITD mutation ( P = 0.028) and lower frequency of C-Kit mutation ( P = 0.0232) than BCL3 low patients. Although there were no significant differences in complete remission and overall survival between BCL3 low and BCL3 high groups, patients with high BCL3 expression markedly shorter overall survival (OS, P = 0.049), relapse-free survival (RFS, P = 0.027) and disease-free survival (DFS, P = 0.042) in M2 AML than low BCL3 expression patients. Additionally, in AMLs of M2 subtype, high BCL3 expression patients had markedly lower complete remission (CR) rate ( P = 0.0317) after the second induction treatment than patients with BCL3 low expression. Thus, these findings indicated that BCL3 appeared as a promising molecular biomarker of pediatric acute myeloid leukemia with unfavorable prognosis.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

BCL3 Expression Is a Potential Prognostic and Predictive Biomarker in Acute Myeloid Leukemia of FAB Subtype M2

Niu

Yang

Chen

et al. 2018

Pathol. Oncol. Res.

View full text Add to dashboard Cite

show abstract

“…It has been pointed out to be upregulated in hematological malignancies, as well as in a wide range of solid tumors [25, 26], including breast cancer, ovarian cancer, colorectal cancer and non-small-cell lung cancer, and it is also associated with the survival and relapse frequency [27–29]. Furthermore, BCL3 has been reported to exhibit anti-apoptotic effect in cancer [30, 31], which plays a proto-oncogene role.…”

Section: Introductionmentioning

confidence: 99%

A four-gene signature predicts survival in clear-cell renal-cell carcinoma

Dai

Wang

et al. 2016

Oncotarget

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Clear-cell renal-cell carcinoma (ccRCC) is the most common pathological subtype of renal cell carcinoma (RCC), accounting for about 80% of RCC. In order to find potential prognostic biomarkers in ccRCC, we presented a four-gene signature to evaluate the prognosis of ccRCC. SurvExpress and immunohistochemical (IHC) staining of tissue microarrays were used to analyze the association between the four genes and the prognosis of ccRCC. Data from TCGA dataset revealed a prognostic prompt function of the four genes (PTEN, PIK3C2A, ITPA and BCL3). Further discovery suggested that the four-gene signature predicted survival better than any of the four genes alone. Moreover, IHC staining demonstrated a consistent result with TCGA, indicating that the signature was an independent prognostic factor of survival in ccRCC. Univariate and multivariate Cox proportional hazard regression analysis were conducted to verify the association of clinicopathological variables and the four genes’ expression levels with survival. The results further testified that the risk (four-gene signature) was an independent prognostic factors of both Overall Survival (OS) and Disease-free Survival (DFS) (P<0.05). In conclusion, the four-gene signature was correlated with the survival of ccRCC, and therefore, may help to provide significant clinical implications for predicting the prognosis of patients.

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The enhancer rare germline variation rs548071605 contributes to lung cancer development

Wang

Yang

et al. 2021

Human Mutation

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Rare germline variations contribute to the missing heritability of human complex diseases including cancers. Given their very low frequency, discovering and testing disease‐causing rare germline variations remains challenging. The tag‐single nucleotide polymorphism rs17728461 in 22q12.2 is highly associated with lung cancer risk. Here, we identified a functional rare germline variation rs548071605 (A>G) in a p65‐responsive enhancer located within 22q12.2. The enhancer significantly promoted lung cancer cell proliferation in vitro and in a xenograft mouse model by upregulating the leukemia inhibitory factor (LIF) gene via the formation of a chromatin loop. Differential expression of LIF and its significant correlation with first progression survival time of patients further supported the lung cancer‐driving effects of the 22q‐Enh enhancer. Importantly, the rare variation was harbored in the p65 binding sequence and dramatically increased the enhancer activity by increasing responsiveness of the enhancer to p65 and B‐cell lymphoma 3 protein, an oncoprotein that assisted the p65 binding. Our study revealed a regulatory rare germline variation with a potential lung cancer‐driving role in the 22q12.2 risk region, providing intriguing clues for investigating the “missing heritability” of cancers, and also offered a useful experimental model for identifying causal rare variations.

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Variant of BCL3 gene is strongly associated with five-year survival of non-small-cell lung cancer patients

Cited by 14 publications

References 41 publications

BCL3 Expression Is a Potential Prognostic and Predictive Biomarker in Acute Myeloid Leukemia of FAB Subtype M2

BCL3 Expression Is a Potential Prognostic and Predictive Biomarker in Acute Myeloid Leukemia of FAB Subtype M2

A four-gene signature predicts survival in clear-cell renal-cell carcinoma

The enhancer rare germline variation rs548071605 contributes to lung cancer development

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