Na Shen

The significant prognostic value of circulating tumor cells in triple-negative breast cancer: a meta-analysis

Background The clinical validity of circulating tumor cells (CTCs) is still controversial in patients with triple-negative breast cancer (TNBC). Methods A comprehensive literature search was performed to identify relevant articles in the PubMed, Web of Science, MEDLINE, and Embase databases through September 2015. The outcomes of interest were disease progression and overall survival. The hazard ratio (HR) and 95% confidence interval (95% CI) were considered the effect indicators and were pooled in meta-analyses under a fixed- or random-effect model according to heterogeneity. Results Ten of the eligible studies were included for a total of 642 enrolled TNBC patients. Overall analyses revealed that the presence of CTCs predicted aggressive disease progression (HR = 2.18, 95% CI = 1.59-2.99, Pheterogeneity = 0.010, I2 = 52.2%) and reduced overall survival (HR = 2.02, 95% CI = 1.59-2.57, Pheterogeneity = 0.169, I2 = 26.6%). Further subgroup analyses demonstrated that CTC-positive patients also had poor disease progression and overall survival in different subsets, including cancer stage. Conclusion Our meta-analysis provides strong evidence that detection of CTC in the peripheral blood is an independent prognosticator of poor survival outcomes for TNBC patients.

Association of lncRNA H19 rs217727 polymorphism and cancer risk in the Chinese population: a meta-analysis

Reports on the relationship between the lncRNA H19 rs217727 polymorphism and the risk of cancer in the Chinese population have been inconsistent. Therefore, we performed a meta-analysis to evaluate this association, by searching the Embase, PubMed, Web of Science, Wanfang, and CNKI databases. Four case-control studies with 3,157 cases and 3,564 controls were selected for this meta-analysis. The odds ratios with 95% confidence intervals were examined using the random effect model. Allelic (A vs. G), dominant (AA + GA vs. GG), recessive (AA vs. GA + GG), and additive (AA vs. GG) genetic models were used to determine the association. Overall, no significant association was observed between the rs217727 polymorphism and cancer susceptibility in any of the four genetic models. Sensitivity analysis revealed that the results were stable in the allelic and dominant genetic models, but those from the recessive and additive models were unstable, which should be treated with caution. Our meta-analysis suggests that the lncRNA H19 rs217727 polymorphism might not be associated with overall cancer risk. However, well-designed, large-scale studies with different ethnic populations need to be conducted in the future to elucidate the potential association.

Association between rs2853669 in TERT gene and the risk and prognosis of human cancer: a systematic review and meta-analysis

The polymorphism rs2853669 within the promoter of telomerase reverse transcriptase gene (TERTp) has been debated about its role in cancer risk and prognosis. Additionally, several studies report inconsistent results concerning the modifying effect of rs2853669 on the prognostic value of TERTp mutations in cancer patients. Here, we performed this meta-analysis to comprehensively evaluate the role of rs2853669 in the risk and prognosis of human cancer, and further assess its modifying impact on TERTp mutations in the survival of cancer patients. We systematically searched literature via PubMed, Web of Science, and EMBASE through July 2016, and included 22 eligible studies. The overall analysis (64,119 cases and 78,988 controls) demonstrated that rs2853669 did not increase or decrease the overall cancer risk. Subsequent analyses also did not reveal any association between rs2853669 and overall cancer prognosis. However, we identified a modifying effect of rs2853669 on TERTp mutations in that, among cancer patients with TERTp mutations, only those carrying the TT genotype had a poor survival (Hazard ratio = 1.56, 95% confidence interval = 1.06-2.28); subgroup analyses by cancer type also supported these results. In conclusion, our findings suggest that rs2853669 could be important for assessing the prognostic value of TERTp mutations. Future large studies are required to further validate our results.The polymorphism rs2853669 within the promoter of telomerase reverse transcriptase gene (TERTp) has been debated about its role in cancer risk and prognosis. Additionally, several studies report inconsistent results concerning the modifying effect of rs2853669 on the prognostic value of TERTp mutations in cancer patients. Here, we performed this meta-analysis to comprehensively evaluate the role of rs2853669 in the risk and prognosis of human cancer, and further assess its modifying impact on TERTp mutations in the survival of cancer patients. We systematically searched literature via PubMed, Web of Science, and EMBASE through July 2016, and included 22 eligible studies. The overall analysis (64,119 cases and 78,988 controls) demonstrated that rs2853669 did not increase or decrease the overall cancer risk. Subsequent analyses also did not reveal any association between rs2853669 and overall cancer prognosis. However, we identified a modifying effect of rs2853669 on TERTp mutations in that, among cancer patients with TERTp mutations, only those carrying the TT genotype had a poor survival (Hazard ratio = 1.56, 95% confidence interval = 1.06-2.28); subgroup analyses by cancer type also supported these results. In conclusion, our findings suggest that rs2853669 could be important for assessing the prognostic value of TERTp mutations. Future large studies are required to further validate our results.

Possible association of CCDC62 rs12817488 polymorphism and Parkinson’s disease risk in Chinese population: a meta-analysis

Conflicting results identifying the association between coiled-coil domain containing 62 (CCDC62) polymorphism, rs12817488, and Parkinson’s disease (PD) have been reported. To clarify whether rs12817488 is related to PD risk in Chinese population, we carried out this meta-analysis by searching literature from PubMed and Embase database regarding this polymorphism. Three eligible studies involving 1616 cases and 1649 controls were included in this meta-analysis. Our results showed statistically significant association between rs12817488 and PD risk in all four genetic models. Stratification by gender revealed similar results in both subgroup in these genetic models except for recessive model, in which rs12817488 was not significantly associated with PD in male subgroup. Unstable result was found in recessive model via sensitivity analysis, and publication bias was observed in recessive model as well, indicating that the pooled result from recessive model should be cautiously treated. Our meta-analysis implicates a possible relationship between rs12817488 and PD risk in Chinese population. Further validation of this association in large sample size study with different gender is warranted.

Mutation analysis of a Chinese family with oculocutaneous albinism

Oculocutaneous albinism (OCA) is an autosomal recessive disorder characterized by either complete lack of or a reduction in melanin biosynthesis in the skin, hair, and eyes. OCA1, the most common and severe type, is caused by mutations in the tyrosinase (TYR) gene. In this study, we report a Chinese family with two members affected by OCA. Blood samples were collected from all family members. Genomic DNA was isolated from blood leukocytes, and all coding exons and adjacent intronic sequences of the TYR gene were examined for mutation analysis using polymerase chain reaction (PCR)-based sequencing. A pedigree chart was drawn, and clinical examinations and paraclinical tests were performed. Compound heterozygous mutations in TYR (c.832C>T and c.929_930insC, which resulted in p.Arg278* and p.Arg311Lysfs*7, respectively) were identified in the two patients with milky skin, white hair, photophobia, and reduced visual acuity, while other family members only carried one of two heterozygous mutations. In addition, a homozygous missense mutation c.814G>A (p.Glu272Lys) in the solute carrier family 45 member 2 (SLC45A2) gene was found in both patients and unaffected family members, suggesting that this may not be a causative mutation. The findings of this study expand the mutational spectrum of OCA. Compound heterozygous mutations (c.832C>T and c.929_930insC) in the TYR gene may be responsible for partial clinical manifestations of OCA, while the homozygous missense mutation c.814G>A (p.Glu272Lys) in the SLC45A2 gene may not be associated with OCA.

FVIII p.Arg1800His mutation is associated with mild/moderate hemophilia A in Chinese population

Sir, Hemophilia A (HA) is the most common Xlinked bleeding disorder caused by absent, reduced, or dysfunction of factor FVIII coagulant activity (FVIII:C) due to mutations in the F8 gene. In mild/ moderate hemophilia A (MHA), bleeding occurs after trauma or surgery.1 F8 gene is located on the X chromosome, comprising 26 exons. F8 is translated into a 2351amino acid polypeptide containing a 19amino acid signal peptide, which will be cleaved to produce a 2332amino acid multidomain glycoprotein composed of 3 Atype domains, 1 B domain, 2 Ctype domains, and 3 small acidic atype regions (A1a1A2a2Ba3A3C1C2). The mature heterodimer FVIII is produced after intracellular cleavage, which is composed of 3 A domains homologous to a Copper binding protein ceruloplasmin, 2 C domains homologous to coagulation FV, and 1 B domain without any known homology. FVIII is released from VWF after specific proteolysis by thrombin, formed of heterotrimer activated FVIII (A1A2A3C1C2). The mutation spectrum of F8 gene is complex, including intron22/1 inversions, large segmental deletions spanning several exons, single nucleotide mutation, and total deletion due to chromosomal structural rearrangements. Many mutations have been included in HGMD (www.hgmd.cf.ac.uk) and EAHAD (www.factorviii-db.org) databases. More than 2703 mutations responsible for HA have been identified, and FVIII p.Arg1800His (Legacy Arg1781His) has been widely reported in patients with MHA in Caucasian population, but seldom identified in Asian population except for a patient in Taiwan.2-6 Herein, two families with MHA patients were studied. Hemizygous FVIII p.Arg1800His mutation was found in all included MHA patients, but these patients showed varied FVIII:C and phenotype, suggesting variable expressivity. This is the first report of FVIII p.Arg1800His mutation in China mainland.

Meta-analysis Reveals the Prognostic Value of Circulating Tumour Cells Detected in the Peripheral Blood in Patients with Non-Metastatic Colorectal Cancer

Detecting circulating tumour cells (CTCs) is considered as effective and minimally invasive technique to predict the prognosis of patients with metastatic colorectal cancer (CRC), but its clinical validity is still conflicting in patients without metastasis. We performed this meta-analysis to evaluate whether detection of CTCs in the peripheral blood can be used as a prognostic marker for patients with non-metastatic CRC. We performed a comprehensive search of the EMBASE, PubMed, and Web of Science databases (up to September 2016). Meta-analyses were conducted using a random-effects model with the hazard ratio (HR) and 95% confidence interval (95% CI) as the effect measures. Twenty studies including 3,687 patients were eligible for inclusion. Overall analyses demonstrated that the presence of CTCs was significantly associated with aggressive disease progression (HRu2009=u20092.57, 95% CIu2009=u20091.64–4.02, Pheterogeneityu2009<u20090.001, I2u2009=u200981.0%) and reduced disease survival (HRu2009=u20092.41, 95% CIu2009=u20091.66–3.51, Pheterogeneityu2009=u20090.002, I2u2009=u200959.7%). Subgroup analyses further supported the prognostic effect of CTCs based on different subsets, including sampling time, detection method and cancer type. Our findings suggest that detection of CTCs in the peripheral blood has the clinical utility to indicate poor prognosis in patients with non-metastatic CRC.

Mutational analysis of a Chinese family with oculocutaneous albinism type 2

Oculocutaneous albinism (OCA) is an autosomal recessive disorder characterized by hypopigmentation of the skin, hair, and eyes accompanied with ophthalmologic abnormalities. Molecular genetic test can confirm the diagnosis of the four subtypes of OCA (OCA1-4). Herein, we report a Chinese family with two patients affected by OCA. Mutations of TYR, OCA2, TYRP1, and SLC45A2 were examined by using PCR-sequencing. Large deletions or duplications of TYR and OCA2 were examined by Multiplex Ligation-dependent Probe Amplification (MLPA) assay. Compound heterozygous mutations of OCA2, (c.808-3C>G and c.2080-2A>G), were identified in both patients characterized with yellow hair and milky skin, heterochromia iridis, and nystagmus. Several computer-assisted approaches predicted that c.808-3C>G and c.2080-2A>G in OCA2 might potentially be pathogenic splicing mutations. No exon rearrangement (deletion/duplication) of TYR and OCA2 was observed in the patients by MLPA analysis. This study suggests that compound heterozygous mutations, (c.808-3C>G and c.2080-2A>G), in OCA2 may be responsible for partial clinical manifestations of OCA.

Evaluating the diagnostic accuracy of the Xpert® MTB/RIF assay on bronchoalveolar lavage fluid: a retrospective study

OBJECTIVEnLimited data on the diagnostic accuracy of the Xpert MTB/RIF assay using bronchoalveolar lavage fluid from patients with suspected pulmonary tuberculosis (PTB) have been reported in China. Therefore, a retrospective study was designed to evaluate the diagnostic accuracy of this assay.nnnMETHODSnClinical, radiological, and microbiological characteristics of 238 patients with suspected PTB were reviewed retrospectively. The sensitivity, specificity, positive predictive value, and negative predictive value for the diagnosis of active PTB were calculated for the Xpert MTB/RIF assay using TB culture or final diagnosis based on clinical and radiological evaluation as the reference standard.nnnRESULTSnThe sensitivity and specificity of the Xpert MTB/RIF assay were 84.5% and 98.9%, respectively, and those for smear microscopy were 36.2% and 100%, respectively, when compared to the culture method. However, compared with the sensitivity and specificity of final diagnosis based on clinical and radiological evaluation, the sensitivity and specificity of the assay were 72.9% and 98.7%, respectively, which were significantly higher than those for smear microscopy.nnnCONCLUSIONSnThe Xpert MTB/RIF assay on bronchoalveolar lavage fluid could serve as an additional rapid diagnostic tool for PTB in a high TB-burden country and improve the time to TB treatment initiation in patients with PTB.

Novel hereditary spherocytosis-associated splice site mutation in the ANK1 gene caused by parental gonosomal mosaicism

Hereditary spherocytosis (HS) is a heterogeneous condition of inherited hemolytic anemia characterized by anemia, jaundice, cholelithiasis and splenomegaly with a prevalence of 1 in 10,000 in China.[1][1] Diagnosis of HS is mainly based on a positive familial history, clinical features and