The prognostic significance of LncRNA BLACAT1 overexpression in various tumors: a meta-analysis.

Objective: Recent studies have revealed increasing evidence that the long non-coding RNA bladder cancer associated transcript 1 (LncRNA BLACAT1) plays an essential role in the emergence of different malignancies. This meta-analysis aimed to evaluate the prognostic significance of LncRNA BLACAT1 in various cancers. Methods: Six electronic databases (PubMed, Embase, Medline, Web of Science, China National Knowledge Infrastructure (CNKI), and the Chinese WanFang database) were comprehensively searched for relevant studies. The analysis of overall survival (OS) and clinicopathological characteristics was conducted. Results: Nineteen studies with 1,559 patients were eventually eligible to be included in this meta-analysis. High expression level of LncRNA BLACAT1 was identified to be linked with shorter OS (HR: 2.02, 95% CI: 1.66-2.46, p < 0.001) and PFS (HR: 2.424, 95% CI: 1.827-3.020, p < 0.001) in cancer patients as opposed to low expression levels. Subgroup analysis showed that analysis model (multivariate or univariate), cut-off value (mean or median), sample size (more or fewer than 100), and cancer type had little effect on OS in multiple tumors. Moreover, high LncRNA BLACAT1 expression was associated with positive lymph node metastasis (HR: 2.29, 95% CI: 1.66-3.16, p < 0.00001), advanced clinical stage (HR: 2.29, 95% CI: 1.65-3.19, p < 0.00001) and worse differentiation status (HR: 0.58, 95% CI: 0.37-0.92, p = 0.02), compared to low LncRNA BLACAT1 expression. Conclusion: The findings highlight that high LncRNA BLACAT1 expression might be detrimental and induce a worse prognosis for cancer patients.

Clinical significance of cytogenetic and molecular genetic abnormalities in 634 Chinese patients with myelodysplastic syndromes.

PURPOSE: To explore the relevance of cytogenetic or molecular genetic abnormalities to clinical variables, including clinical and laboratory characteristics and prognosis in Chinese patients with myelodysplastic syndromes (MDS). METHODS: A total of 634 consecutive patients diagnosed with MDS at The First Affiliated Hospital, Zhejiang University School of Medicine from June 2008 to May 2018 were retrospectively included in this study. All patients had evaluable cytogenetic analysis, and 425 patients had MDS-related mutations sequencing. RESULTS: 38.6% of patients displayed abnormal karyotypes. The most common cytogenetic abnormality was +8 (31%). Sole +8 was related to female (p = 0.002), hemoglobin >10 g/dL (p = 0.03), and <60 years old (p = 0.046). TP53 mutations were associated with complex karyotype (CK) (p < 0.001). DNMT3A mutations correlated with -Y (p = 0.01) whereas NRAS mutations correlated with 20q- (p = 0.04). The overall survival (OS) was significantly inferior in patients with +8 compared with those with normal karyotype (NK) (p = 0.003). However, the OS of sole +8 and +8 with one additional karyotypic abnormality was not different from NK (p = 0.16), but +8 with two or more abnormalities had a significantly shorter OS than +8 and +8 with one additional karyotypic abnormality (p = 0.02). In multivariable analysis, ≥60 years old, marrow blasts ≥5% and TP53 mutations were independent predictors for poor OS (p < 0.05), whereas SF3B1 mutations indicated better prognosis. Male IDH1 and IDH2 mutations and marrow blasts ≥5% were independent risk factors for worse leukemia free survival (LFS) (p < 0.05). CONCLUSION: In this population of Chinese patients, trisomy 8 is the most common karyotypic abnormality. Patients with +8 showed a poorer OS compared with patients with NK. Sole +8 and +8 with one additional karyotypic abnormality had similar OS with NK, whereas +8 with two or more abnormalities had a significantly shorter OS. DNMT3A mutations correlated with -Y and NRAS mutations correlated with 20q-. TP53 mutations were associated with CK and had a poor OS. SF3B1 mutations indicated a favorable OS. IDH1 and IDH2 mutations independently indicated inferior LFS.

Long non-coding RNA zinc finger antisense 1 functions as an oncogene in acute promyelocytic leukemia cells.

Despite progress in the diagnosis and treatment of acute promyelocytic leukemia (APL), its prognosis remains poor. Multiple studies have shown that long non-coding RNAs (lncRNAs) are involved in carcinogenesis and metastasis. The present study assessed the function of the lncRNA zinc finger antisense 1 (ZFAS1) in APL. In a cohort of 33 patients, ZFAS1 was significantly overexpressed compared with the level in healthy controls. To investigate the specific mechanisms of this upregulation, in vitro studies showed that silencing of ZFAS1 by small interfering RNA significantly inhibited cell proliferation in APL cells. Moreover, downregulation of ZFAS1 increased cellular apoptosis, decreased expression of B-cell lymphoma-2 and of induced myeloid leukemia cell differentiation protein Mcl-1, increased the expression of apoptosis regulator BAX and promoted the release of cytochrome c and Diablo homolog mitochondrial into the cytoplasm. In conclusion, these data indicate that ZFAS1 may serve as an oncogene in APL and may thus be a useful target for future clinical management.

[Analysis of the karyotype abnormalities and its prognostic in 298 patients with myelodysplastic syndrome].

OBJECTIVE: To investigate the relationship between cytogenetic markers with World Health Organization (WHO) classification, disease progress and prognosis in cases with primary myelodysplastic syndromes (MDS). METHODS: 298 patients with de novo MDS from the first affiliated hospital of medical school, Zhejiang University were enrolled in the retrospective analysis of WHO classification, karyotype, and prognosis. Follow-up study was also conducted. RESULTS: The WHO classifications at first diagnosis were as follows: refractory cytopenia with unilineage dysplasia (RCUD), 18 cases; refractory anemia with ring sideroblasts (RARS), 8 cases; refractory cytopenia with multiline dysplasia (RCMD), 104 cases; refractory anemia with excess blasts-1, 76 cases; refractory anemia with excess blasts-2, 85 cases; MDS unclassified (MDS-U), 5 cases involved; and single del (5q), 2 cases. 39.6% of MDS patients carried karyotypic abnormalities. Among them, the frequency of numerical abnormalities, structural abnormalities and the existence of composite abnormalities were 45, 31, and 42, respectively. The composite abnormalities were unbalanced translocations and complex chromosomal abnormalities. The incidence of both karyotypic abnormalities and complex chromosomal abnormalities in RAEB group was higher than that in non-RAEB group (P<0. 05). An analysis based on IPSS-R Scoring System showed that advanced risk stratification (except the low-risk group) gradually enhanced the incidence of karyotypic abnormalities (P<0.05). In addition, the probability of evolution to leukemia increased with the higher IPSS-R score (P<0.05). In RAEB group, the cases with +8 chromosome, accounting for 19.5% of karyotypic abnormalities, had worse prognosis than those with normal chromosomes. CONCLUSION: Karyotype was identified with an independent risk factor in MDS patients. Therefore, the information on cytogenetic analysis was critical for diagnosis, prognosis and individual treatment. MDS patients presenting+8 chromosome, an intermediate risk factor, were associated with a poorer outcome compared to cases with normal chromosomes in RAEB group.