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1.
Nguyen Xuong Duong Minh-Khang Le Tetsuo Kondo Takahiko Mitsui 《Journal of cellular and molecular medicine》2023,27(1):66-75
This study aimed to reveal the prognostic role of the Hippo pathway in different histopathological subtypes of renal cell carcinoma (RCC). The TCGA-KIRC (n = 537), TCGA-KIRP (n = 291) and TCGA-KICH (n = 113), which contain data about clear cell (ccRCC), papillary (pRCC) and chromophobe RCC (chRCC), respectively, were investigated. Gene Set Variation Analysis was used to compare the activity of many pathways within a single sample. Oncogenic pathway-related expression differed between cases of ccRCC involving low and high Hippo pathway activity. There were two subsets of ccRCC, in which the cancer exhibited lower and higher Hippo signalling activity, respectively, compared with normal tissue. In the ccRCC cohort, lower Hippo pathway activity was associated with a higher clinical stage (p < 0.001). The Hippo pathway (HR = 0.29; 95% CI = 0.17–0.50, p < 0.001), apoptosis (HR = 6.02; 95% CI = 1.47–24.61; p = 0.013) and the p53 pathway (HR = 0.09; 95% CI = 0.02–0.36; p < 0.001) were identified as independent prognostic factors for ccRCC. The 5-year overall survival of the ccRCC patients with low and high Hippo pathway activity were 51.9% (95% CI = 45.0–59.9) and 73.6% (95% CI = 67.8–79.9), respectively. In conclusion, the Hippo pathway plays an important role in the progression of ccRCC. Low Hippo pathway activity is associated with poor outcomes in ccRCC, indicating the tumour suppressor function of this pathway. 相似文献
2.
Xi Tian Wen-Hao Xu Aihetaimujiang Anwaier Hong-Kai Wang Fang-Ning Wan Da-Long Cao Wen-Jie Luo Guo-Hai Shi Yuan-Yuan Qu Hai-Liang Zhang Ding-Wei Ye 《Journal of cellular and molecular medicine》2021,25(8):3898-3911
This study aims to construct a robust prognostic model for adult adrenocortical carcinoma (ACC) by large-scale multiomics analysis and real-world data. The RPPA data, gene expression profiles and clinical information of adult ACC patients were obtained from The Cancer Proteome Atlas (TCPA), Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA). Integrated prognosis-related proteins (IPRPs) model was constructed. Immunohistochemistry was used to validate the prognostic value of the IPRPs model in Fudan University Shanghai Cancer Center (FUSCC) cohort. 76 ACC cases from TCGA and 22 ACC cases from GSE10927 in NCBI’s GEO database with full data for clinical information and gene expression were utilized to validate the effectiveness of the IPRPs model. Higher FASN (P = .039), FIBRONECTIN (P < .001), TFRC (P < .001), TSC1 (P < .001) expression indicated significantly worse overall survival for adult ACC patients. Risk assessment suggested significantly a strong predictive capacity of IPRPs model for poor overall survival (P < .05). IPRPs model showed a little stronger ability for predicting prognosis than Ki-67 protein in FUSCC cohort (P = .003, HR = 3.947; P = .005, HR = 3.787). In external validation of IPRPs model using gene expression data, IPRPs model showed strong ability for predicting prognosis in TCGA cohort (P = .005, HR = 3.061) and it exhibited best ability for predicting prognosis in GSE10927 cohort (P = .0898, HR = 2.318). This research constructed IPRPs model for predicting adult ACC patients’ prognosis using proteomic data, gene expression data and real-world data and this prognostic model showed stronger predictive value than other biomarkers (Ki-67, Beta-catenin, etc) in multi-cohorts. 相似文献
3.
The aim of our meta-analysis was to quantitatively summarize the association of TYK2 gene polymorphisms with autoimmune and
inflammatory diseases. 11 studies that included data from 21497 cases and 22647 controls were identified. OR was used as a
measure of the effect of the association in a fixed/random effect model. Meta-analysis was performed for six TYK2 gene polymorphisms
(rs34536443, rs2304256, rs280523, rs280519, rs12720270 and rs12720356). Significant association was found in rs34536443 (C
versus G: OR = 0.76, 95% CI = 0.69–0.84, P < 0.00001; GC + CC versus GG: OR = 0.78, 95% CI = 0.68–0.90, P = 0.0005; CC versus GG + GC: OR = 0.76, 95% CI = 0.28–2.05, P = 0.58; CC versus GG: OR = 0.74, 95% CI = 0.27–2.02, P = 0.56; GC versus GG: OR = 0.78, 95% CI = 0.68–0.90, P = 0.0006) and rs2304256 (A versus C: OR = 0.78, 95% CI = 0.70–0.87, P < 0.0001; CA + AA versus CC: OR = 0.69, 95% CI = 0.59–0.81, P < 0.0001; AA versus CC + CA: OR = 0.75, 95% CI = 0.66–1.00, P = 0.05; AA versus CC: OR = 0.64, 95% CI = 0.47–0.86, P = 0.003; CA versus CC: OR = 0.70, 95% CI = 0.60–0.83, P < 0.0001) in TYK2 gene, but not for the other polymorphisms (rs280523, rs280519, rs12720270, and rs12720356). This meta-analysis
demonstrates that autoimmune and inflammatory diseases is associated with TYK2 gene rs34536443 and rs2304256 polymorphisms,
but not rs280523, rs280519, rs12720270 and rs12720356. 相似文献
4.
BackgroundGastrointestinal (GI) cancers represent a diverse group of diseases. We assessed differences in geographic and racial disparities in cancer-specific mortality across subtypes, overall and by patient characteristics, in a geographically and racially diverse US population.MethodsClinical, sociodemographic, and treatment characteristics for patients diagnosed during 2009–2014 with colorectal cancer (CRC), pancreatic cancer, hepatocellular carcinoma (HCC), or gastric cancer in Georgia were obtained from the Surveillance, Epidemiology, and End Results Program database. Patients were classified by geography (rural or urban county) and race and followed for cancer-specific death. Multivariable Cox proportional hazards models were used to calculate stratified hazard ratios (HR) and 95% confidence intervals (CIs) for associations between geography or race and cancer-specific mortality.ResultsOverall, 77% of the study population resided in urban counties and 33% were non-Hispanic Black (NHB). For all subtypes, NHB patients were more likely to reside in urban counties than non-Hispanic White patients. Residing in a rural county was associated with an overall increased hazard of cancer-specific mortality for HCC (HR = 1.15, 95% CI = 1.02–1.31), pancreatic (HR = 1.11, 95% CI = 1.03–1.19), and gastric cancer (HR = 1.17, 95% CI = 1.03–1.32) but near-null for CRC. Overall racial disparities were observed for CRC (HR = 1.18, 95% CI = 1.11–1.25) and HCC (HR = 1.12, 95% CI = 1.01–1.24). Geographic disparities were most pronounced among HCC patients receiving surgery. Racial disparities were pronounced among CRC patients receiving any treatment.ConclusionGeographic disparities were observed for the rarer GI cancer subtypes, and racial disparities were pronounced for CRC. Treatment factors appear to largely drive both disparities. 相似文献
5.
Meiyun Kang Xiaojie Ding Ming Xu Haixia Zhu Sang Liu Meilin Wang Dongmei Wu Na Tong Weida Gong Jianwei Zhou Zhengdong Zhang 《Gene》2014
A recent genome-wide association study (GWAS) on esophageal squamous-cell carcinoma (ESCC) among Chinese people has discovered a novel single nucleotide polymorphism (SNP) rs10484761 on 6p21.1 region. We hypothesized that SNP rs10484761 T/C is associated with survival of gastric cancer. We genotyped SNP rs10484761 in 940 gastric cancer patients treated with surgical resection. Kaplan–Meier survival analysis, log-rank test, and Cox proportional hazard models were used to evaluate the association between the SNP rs10484761 and gastric cancer survival. In the dominant model, those who carry TC/CC genotypes had a significant shorter survival time (log-rank P = 0.005), especially in the subgroups of aged male patients, cardia intestinal tumor (HR = 1.41, 95% CI = 1.08–1.84 for cardia cancer and HR = 1.64, 95% CI = 1.14–2.37 for intestinal-type), tumor size ≤ 5 cm (HR = 1.41, 95% CI = 0.56–0.99), T1 depth invasion (HR = 2.34, 95% CI = 1.20–4.56), lymph node metastasis (HR = 1.51, 95% CI = 1.19–1.96), no distant metastasis (HR = 1.33, 95% CI = 1.05–1.68), TNM stage III + IV (HR = 1.50, 95% CI = 1.13–1.98), and with chemotherapy (HR = 1.53, 95% CI = 1.17–1.99). The results indicated that SNP rs10484761 was associated with prognosis of gastric cancer, suggesting that this genetic variant may serve as a potential marker to predict the survival of gastric cancer in Chinese population. 相似文献
6.
Thrombospondin 1 (THBS1), a multi-domain glycoprotein, is secreted from astrocytes and promotes synaptogenesis. Increasing
evidence has suggested that not only various markers for synaptic pathology, but also astrocytes are affected in schizophrenia.
In this study, we investigated whether coding region single nucleotide polymorphisms (cSNPs) of the THBS1 gene were associated with schizophrenia and with the clinical symptoms of schizophrenia patients. We genotyped two cSNPs
[rs2228261 (Asn470Asn) and rs2292305 (Thr523Ala)] using direct sequencing in 220 schizophrenia patients and 376 control subjects.
In this study, rs2228261 revealed significant association with schizophrenia in both codominant (TT vs. CC, P = 0.009, OR = 2.10, 95% CI = 1.23–3.59) and recessive models (TT vs. CC/CT, P = 0.0012, OR = 2.28, 95% CI = 1.38–3.77). Also, rs2292305 was associated with schizophrenia in the recessive model (GG vs.
AA/AG, P = 0.0052, OR = 2.05, 95% CI = 1.24–3.38). Additionally, in the analysis of the haplotype, the CA and TG haplotypes consisting
of rs2228261 and rs2292305 were associated with schizophrenia in the dominant (P = 0.019, OR = 1.79, 95% CI = 1.10–2.90) and recessive models, respectively (P = 0.0086, OR = 0.51, 95% CI = 0.31–0.84). In further analysis according to the clinical symptoms, rs2292305 showed a weak
association with the poor concentration symptoms of schizophrenia patients in the dominant model (AG/GG vs. AA, P = 0.024, OR = 2.04, 95% CI = 1.09–3.83). The results suggest that the THBS1 gene may contribute to the susceptibility of schizophrenia. 相似文献
7.
Feng Shi Xiaoxia Pang Guangjing Li Zhihong Chen Mingyou Dong Junli Wang 《Journal of cellular and molecular medicine》2022,26(9):2658
The aim of this study was to investigate the effects of forkhead box protein P3 (FOXP3) intron single nucleotide variants (SNVs) in high‐risk human papilloma virus (HR‐HPV) infection and cervical cancer (CC) malignant lesions. We performed FOXP3 genotyping in 350 patients with CC and 350 healthy controls using the ImLDR multiple single nucleotide polymorphism genotyping technology. The heterozygous mutation TC in rs2294021 decreased the risk of HR‐HPV infection and CC malignant lesions (TC vs. TT: OR = 0.71, 95% CI = 0.51–0.99); the dominant model TC+CC and allele C in rs2294021 decreased the risk of CC malignant lesions (TC+CC vs. TT: OR = 0.69, 95% CI = 0.50–0.95; C vs. T: OR = 0.78, 95% CI = 0.63–0.97). The heterozygous mutation GA, dominant model GA+AA and allele A in rs3761549 also decreased the risk of HR‐HPV infection and CC malignant lesions (GA vs. GG: OR = 0.70, 95% CI = 0.51–0.96; GA+AA vs. GG: OR = 0.69, 95% CI = 0.51–0.94; A vs. G: OR = 0.75, 95% CI = 0.58–0.96). Patients with CC and HR‐HPV infection carrying rs2294021 TC and rs3761549 GA had lower expression of FOXP3 protein. Haplotype analysis revealed that T‐C‐A decreased the risk of HR‐HPV infection. Furthermore, we found a significant association between immune cells infiltration and prognosis in patients with CC. Our findings demonstrated that rs2294021 and rs3761549 variants may protect against HR‐HPV and CC malignant lesions by downregulating FOXP3 and that FOXP3 was associated with immune cells infiltration, which affected the prognosis of CC. 相似文献
8.
To evaluate the association of the IBD5 locus to the predisposition of inflammatory bowel diseases (IBDs), a series of meta-analyses
between five IBD5 variants (OCTN1 C1672T, OCTN2 G-207C, OCTN1/2 TC haplotype, IGR2096a_1, IGR2198a_1 and IGR2230a_1) and Crohn’s disease (CD) and ulcerative colitis (UC) were performed, which included a total of 26 studies. Overall, five
IBD5 variants in a per-allele model of inheritance were significantly associated with elevated CD risk (for OCTN1: OR = 1.23, 95% CI = 1.16–1.30, P < 0.001; for OCTN2: OR = 1.20, 95% CI = 1.11–1.30, P < 0.001; for IGR2096a_1: OR = 1.36, 95% CI = 1.24–1.46, P < 0.001; for IGR2198a_1: OR = 1.34, 95% CI = 1.24–1.46, P < 0.001; for IGR2230a_1: OR = 1.35, 95% CI = 1.23–1.48, P < 0.001) and OCTN1/2 TC haplotype (OR = 1.32, 95% CI = 1.22–1.43, P < 0.001). In the subgroup analysis, the statistically significant associations were also observed in adult- and pediatric-onset
CD and in Caucasians for five IBD5 variants and the OCTN1/2 TC haplotype. A statistically significant increase in the risk of UC was detected in a recessive model of inheritances for
OCTN1 (OR = 1.23, 95% CI = 1.08–1.40, P < 0.001), OCTN2 (OR = 1.18, 95% CI = 1.05–1.33, P = 0.006), IGR2096a_1 (OR = 1.37, 95% CI = 1.15–1.62, P < 0.001) and IGR2198a_1 (OR = 1.35, 95% CI = 1.10–1.66, P = 0.004); the increased risks of UC were maintained in the adult and Caucasian subgroups, but not the pediatric subgroup.
In summary, our results suggested that the IBD5 locus contributes to the susceptibility of CD in a per-allele manner in adults,
children and Caucasians, and the locus contributes to the susceptibility of UC in a recessive manner in adult and Caucasian
populations. 相似文献
9.
Zhang Y Chen GQ Ji Y Huang B Shen WS Deng LC Xi L Cao XM 《Molecular biology reports》2012,39(5):6203-6211
Published studies on the relationships between 5,10-methylenetetrahydrofolate reductase (MTHFR) polymorphisms and lung cancer
risk have been conflicting. To derive a more precise estimation of the relationship, a meta-analysis was performed. Odds ratios
(ORs) with 95% confidence intervals (CIs) were estimated to assess the association between MTHFR C677T and A1298C polymorphisms
and lung cancer risk. A total of 15 studies including 10,753 cases and 11,275 controls described C677T genotypes, among which
11 articles totalling 6,161 cases and 7,684 controls described A1298C genotypes, were also involved in this meta-analysis.
Overall, no significantly elevated lung cancer risk was found in any genetic models when all studies were pooled. For C677T
polymorphism: (TT vs. CC: OR = 1.17, 95% CI = 0.97–1.42; TC vs. CC: OR = 1.06, 95% CI = 0.94–1.20; dominant model: OR = 1.09,
95% CI = 0.96–1.24; and recessive model: OR = 1.08, 95% CI = 0.95–1.24); for A1298C polymorphism: (CC vs. AA: OR = 1.04, 95%
CI = 0.91–1.19; AC vs. AA: OR = 0.98, 95% CI = 0.91–1.06; dominant model: OR = 0.99, 95% CI = 0.92–1.06; and recessive model:
OR = 1.05, 95% CI = 0.92–1.20). In the subgroup analyses, the results showed that 677T varients could decrease lung cancer
risk in female (OR = 0.63, 95% CI = 0.41–0.95, P-value = 0.03, 677CC as reference). No evidence of any associations of MTHFR A1298C polymorphism with lung cancer was found
in overall or subgroup analyses. Our meta-analysis supports that the common polymorphisms of C677T and A1298C in MTHFR gene
are not susceptibility gene for lung cancer from currently available evidence. 相似文献
10.
Stewart G. Martin Siwei Zhang Song Yang Behnaz Saidy Suha Deen Sarah J. Storr 《Journal of cellular and molecular medicine》2020,24(16):9165-9175
Dopamine and cyclic‐AMP activated phosphoprotein Mr32kDa (DARPP‐32) is a central signalling protein in neurotransmission. Following DARPP‐32 phosphorylation by protein kinase A (PKA), DARPP‐32 becomes a potent protein phosphatase 1 (PP1) inhibitor. DARPP‐32 can itself inhibit PKA following DARPP‐32 phosphorylation by cyclin‐dependent kinase 5 (Cdk5). Increasing evidence indicates a role for DARPP‐32 and its associated signalling pathways in cancer; however, its role in ovarian cancer remains unclear. Using immunohistochemistry, expression of DARPP‐32, PP1 and Cdk5 was determined in a large cohort of primary tumours from ovarian cancer patients (n = 428, 445 and 434 respectively) to evaluate associations between clinical outcome and clinicopathological criteria. Low cytoplasmic and nuclear DARPP‐32 expression was associated with shorter patient overall survival and progression‐free survival (P = .001, .001, .004 and .037 respectively). Low nuclear and cytoplasmic DARPP‐32 expression remained significantly associated with overall survival in multivariate Cox regression (P = .045, hazard ratio (HR) = 0.734, 95% confidence interval (CI) = 0.542‐0.993 and P = .001, HR = 0.494, 95% CI = 0.325‐0.749, respectively). High cytoplasmic and nuclear PP1 expression was associated with shorter patient overall survival and high cytoplasmic PP1 expression with shorter progression‐free survival (P = .005, .033, and .037, respectively). High Cdk5 expression was associated with shorter progression‐free survival (P = .006). These data suggest a role for DARPP‐32 and associated signalling kinases as prognostic markers with clinical utility in ovarian cancer. 相似文献
11.
12.
Yuhualei Pan Jian-Hua Zhang Lianhe Zhao Jin-Cheng Guo Song Wang Yushang Zhao Shaoxin Tao Huan Wang Yan-Bing Zhu 《Journal of cellular biochemistry》2020,121(7):3593-3605
Glioblastoma multiforme (GBM) is a highly malignant brain tumor. We explored the prognostic gene signature in 443 GBM samples by systematic bioinformatics analysis, using GSE16011 with microarray expression and corresponding clinical data from Gene Expression Omnibus as the training set. Meanwhile, patients from The Chinese Glioma Genome Atlas database (CGGA) were used as the test set and The Cancer Genome Atlas database (TCGA) as the validation set. Through Cox regression analysis, Kaplan-Meier analysis, t-distributed Stochastic Neighbor Embedding algorithm, clustering, and receiver operating characteristic analysis, a two-gene signature (GRIA2 and RYR3) associated with survival was selected in the GSE16011 dataset. The GRIA2-RYR3 signature divided patients into two risk groups with significantly different survival in the GSE16011 dataset (median: 0.72, 95% confidence interval [CI]: 0.64-0.98, vs median: 0.98, 95% CI: 0.65-1.61 years, logrank test P < .001), the CGGA dataset (median: 0.84, 95% CI: 0.70-1.18, vs median: 1.21, 95% CI: 0.95-2.94 years, logrank test P = .0017), and the TCGA dataset (median: 1.03, 95% CI: 0.86-1.24, vs median: 1.23, 95% CI: 1.04-1.85 years, logrank test P = .0064), validating the predictive value of the signature. And the survival predictive potency of the signature was independent from clinicopathological prognostic features in multivariable Cox analysis. We found that after transfection of U87 cells with small interfering RNA, GRIA2 and RYR3 influenced the biological behaviors of proliferation, migration, and invasion of glioblastoma cells. In conclusion, the two-gene signature was a robust prognostic model to predict GBM survival. 相似文献
13.
Ku70 plays an important role in the DSBR (DNA double-strand breaks repair) and maintenance of genomic integrity. Genetic variations
within human Ku70 have been demonstrated to be associated with increased risk of several types of cancers. In this hospital-based
case–control study, we aimed to investigate whether a single nucleotide polymorphism (SNP) in the promoter region (rs2267437)
of Ku70 gene is associated with susceptibility to breast cancer in Chinese Han population. A total of 293 patients with breast
cancer and 301 age-matched healthy controls were enrolled in this study. The Ku70 −1310C/G polymorphism was determined by
polymerase chain reaction-restriction fragment length polymorphism (PCR–RFLP) analysis. A significant difference in genotype
distribution and allele frequency was observed between patients and controls. The CG or GG carries were at higher risk of
breast cancer compared with the CC homozygotes (OR = 1.43, 95% CI = 1.02–2.00, P = 0.038 and OR = 3.53, 95% CI = 1.60–7.80, P = 0.002, respectively). Further stratification analysis revealed that G allele was associated with an increased risk of breast
cancer among premenopausal women (OR = 1.68, 95% CI = 1.21–2.33, P = 0.002), but not in postmenopausal women (OR = 1.33, 5% CI = 0.85–2.10, P = 0.216). Our study suggests that the Ku70 −1310C/G promoter polymorphism may be a susceptibility factor for breast cancer
in Chinese Han population. 相似文献
14.
The aim of this study was to determine whether the interleukin-10 (IL-10) polymorphisms confer susceptibility to rheumatoid
arthritis (RA). A meta-analysis was conducted on the associations between the IL-10 −1082 G/A, −592 C/A, −892 C/T and IL-10.R
polymorphisms and RA using; (1) allele contrast, (2) the recessive model, (3) the dominant model, and (4) the additive model.
A total of 16 studies (19 comparisons) involving 2647 RA patients and 3383 controls were considered in the meta-analysis.
Meta-analysis of the IL-10 −1082 G/A polymorphism showed no association with RA in the study subjects, or in European or Asian
subjects. However, meta-analysis of the −1082 G allele in 4 studies in Hardy–Weinberg equilibrium showed a significant association
with RA (OR = 1.217, 95% CI = 1.027–1.442, P = 0.0236). In contrast, meta-analysis of the C allele, the CC genotype, and of the CC versus the AA genotype of the IL-10
−592 C/A polymorphism showed significant associations with RA. The overall ORs of the associations between the C allele and
RA were 0.684 and 0.758 (95% CI = 0.494–0.946, P = 0.022; 95% CI = 0.475–1.210, P = 0.045) in all study subjects and Asians. Meta-analysis of the CC + CT versus TT genotype and of the CC versus TT genotype
of the IL-10 −892 C/T polymorphism revealed significant associations with RA. The overall OR of the association between the
C allele carrier and RA was 0.552 (95% CI = 0.375–0.812, P = 0.003). No association was found between the IL10.R2 alleles and RA. This meta-analysis suggests that the IL-10 −592 C/A
polymorphism confers susceptibility to RA in Asians and that the IL-10 −1082 G/A and −892 C/T polymorphisms are associated
with RA susceptibility. These findings suggest the IL-10 genes confer susceptibility to RA. 相似文献
15.
Evidence suggested that interleukin-10 (IL-10) may be involved in the etiology of gastric cancer (GC). However, epidemiological
studies on the association between IL-10-1082 promoter polymorphism and GC risk are still ambiguous. To quantitatively summarize
the evidence for such a relationship, we performed a meta-analysis. Systemic searches of the PubMed and Medline databases
were performed, with the last report up to July 2011. Crude odds ratios (ORs) with 95% confidence intervals (CIs) were used
to assess the strength of association. 22 independent studies including 4,289 cases and 5,965 controls were involved in this
meta-analysis. Obvious association was found when all studies were pooled into the meta-analysis (A vs. G: OR = 0.489, 95%
CI = 0.335–0.713, P < 0.001). In the subgroup analysis by ethnicity, we observed significant associations in Asians (A vs. G: OR = 0.651, 95%
CI = 0.506–0.838, P = 0.001; AA vs. GG: OR = 0.482, 95% CI = 0.328–0.709, P < 0.001; AA/AG vs. GG: OR = 0.711, 95% CI = 0.527–0.959, P = 0.025; AA vs. AG/GG: OR = 0.701, 95% CI = 0.520–0.944, P = 0.019) and Caucasians (A vs. G: OR = 0.365, 95% CI = 0.140–0.949, P = 0.039), but not in Latino population. When stratified analysis by control sources, our results indicated that A allele
decreased approximately 48% risk among population-based studies (A vs. G: OR = 0.524, 95% CI = 0.374–0.733, P < 0.001). Taken together, this meta-analysis suggests that IL-10-1082 polymorphism is associated with GC risk. 相似文献
16.
Wenchao Yang Zhenmin Zhu Jin Wang Wei Ye Yong Ding 《Journal of cellular and molecular medicine》2014,18(12):2466-2477
Emerging evidence shows that interleukin (IL)‐10 gene polymorphisms can regulate its expression level and thus influence person's susceptibility to preeclampsia. However, various published results were inconsistent. To explore the association between maternal IL‐10 gene polymorphisms and preeclampsia, we performed a meta‐analysis based upon 11 individual studies here. Our meta‐analysis results indicated that IL‐10 ‐819C/T (C versus T, OR = 1.28, 95% CI = 1.08–1.50, P = 0.003) and ‐592C/A (C versus A, OR = 1.28, 95% CI = 1.03–1.59, P = 0.03) polymorphisms were associated with preeclampsia. Although there was no overall association between ‐1082A/G polymorphism and preeclampsia (G versus A, OR = 0.93, 95% CI = 0.77–1.13, P = 0.49), such association existed among Asian (G versus A, OR = 1.29, 95% CI = 1.04–1.60, P = 0.02) and South American (G versus A, OR = 0.72, 95% CI = 0.54–0.94, P = 0.02) populations in the subgroup analysis stratified by continents. 相似文献
17.
Zonglin Chen Xianyu Chen Enxiang Zhou Ganlong Chen Ke Qian Xia Wu Xiongying Miao Zhonghua Tang 《PloS one》2014,9(4)
Background
The prognostic effect of tumor infiltrating CD8+ cytotoxic lymphocytes (CTLs) in breast cancer is controversial. We analyzed the association between CD8+ CTLs and survival of untreated node-negative breast cancer patients.Material and Methods
CD8+ CTLs infiltrate was evaluated by immunostaining in a cohort of 332 node-negative breast cancer patients with a median follow-up of 152 months. The prognostic significance of CD8+ CTLs for disease-free survival (DFS) and breast cancer-specific overall survival (OS) was evaluated with Kaplan-Meier survival analysis as well as univariate analysis and multivariate Cox analysis adjusted for age at diagnosis, pT stage, histological grade, estrogen receptor (ER) status, progesterone receptor (PR) status, Ki-67 expression and human epidermal growth factor receptor 2 (HER-2) status.Results
285 (85.8%) patients showed strong CD8+ CTLs infiltrate positive status. Univariate analysis showed that CD8+ CTLs had statistically significant association with DFS (P = 0.004, hazard ratio [HR] = 0.454, 95% confidence interval [CI] = 0.265–0.777) and OS (P = 0.014, HR = 0.430, 95% CI = 0.220–0.840) in the entire cohort. The significance of CD8+ CTLs was especially strong in ER negative, HER-2 negative and ER, PR, HER-2 triple-negative breast cancers. In Kaplan-Meier analysis, CD8+ CTLs had significant effect on prognosis of patients (Log-rank test: P = 0.003 for DFS and P = 0.011 for OS), independent of established clinical factors for DFS (P = 0.002, HR = 0.418, 95% CI = 0.242–0.724) as well as for OS (P = 0.009, HR = 0.401, 95% CI = 0.202–0.797). 相似文献18.
Jiannan Tu Zhixing Kuang Xiaoliang Xie Shizhen Wu Ting Wu Shengchi Chen 《Journal of cellular and molecular medicine》2021,25(1):84-95
Current international prognostic index is widely questioned on the risk stratification of peripheral T-cell lymphoma and does not accurately predict the outcome for patients. We postulated that multiple mRNAs could combine into a model to improve risk stratification and helping clinicians make treatment decisions. In this study, the gene expression profiles were downloaded from the Gene Expression Omnibus (GEO) database. Weighted gene co-expression network analysis (WGCNA) was used to screening genes in selected module which most closely related to PTCLs, and then built a mRNA signature using a LASSO Cox regression model and validated the prognostic accuracy of it. Finally, a nomogram was constructed and the performance was assessed. A total of 799 WGCNA-selected mRNAs in black module were identified, and a mRNA signature which based on DOCK2, GSTM1, H2AFY, KCNAB2, LAPTM5 and SYK for PTCLs was developed. Significantly statistical difference can be seen in overall survival of PTCLs between low-risk group and high-risk group (training set:hazard ratio [HR] 4.3, 95% CI 2.4-7.4, P < .0001; internal testing set:hazard ratio [HR] 2.4, 95% CI 1.2-4.8, P < .01; external testing set:hazard ratio [HR] 2.3, 95% CI 1.10-4.7, P = .02). Furthermore, multivariate regression demonstrated that the signature was an independently prognostic factor. Moreover, the nomogram which combined the mRNA signature and multiple clinical factors suggesting that predicted survival probability agreed well with the actual survival probability. The signature is a reliable prognostic tool for patients with PTCLs, and it has the potential for clinicians to implement personalized therapeutic regimen for patients with PTCLs. 相似文献
19.
Behnaz Saidy Emad A. Rakha Andrew R. Green Ian O. Ellis Stewart G. Martin Sarah J. Storr 《Journal of cellular and molecular medicine》2020,24(11):6263-6271
Cyclin-dependent kinase 5 (Cdk5) is an atypical member of the cyclin-dependent kinase family and functions as a serine/threonine kinase that can be activated by non-cyclin binding activators p35 or p39. Cdk5 expression and activity has been linked with the development and progression of cancer; however, its expression in breast cancer has not been fully described. Protein expression of Cdk5 was determined in a large cohort of early-stage invasive breast cancer tumours (n = 1110) with long-term follow-up data using immunohistochemistry. Expression of CDK5 mRNA was assessed in the METABRIC cohort (n = 1980). Low nuclear and cytoplasmic expression of Cdk5 expression was significantly associated with shorter breast cancer-specific survival (P = .004 and P = .001, respectively). Importantly, low nuclear and cytoplasmic expression of Cdk5 remained associated with survival in multivariate analysis, including potentially confounding factors (hazard ratio (HR) = 0.612, 95% confidence interval (CI) = 0.418-0.896, P = .011 and HR = 0.507, 95% CI = 0.318-0.809, P = .004, respectively). In addition, low nuclear and cytoplasmic expression of Cdk5 was significantly associated with clinicopathological criteria associated with adverse patient prognosis. Low CDK5 mRNA expression was associated with shorter patient survival (P = .005) in the METABRIC cohort; no associations between copy gain or loss and survival were observed. These data suggest that low Cdk5 expression is associated with poor clinical outcome of breast cancer patients and may be of clinical relevance. 相似文献
20.
Published data on the association between lymphocyte-specific protein 1 (LSP1) rs3817198T>C polymorphism and breast cancer
risk are inconclusive. Hence, we conducted a meta-analysis of the LSP1 gene and risk of breast cancer to obtain the most reliable
estimate of the association. PubMed, Embase and Web of Science databases were searched. Crude odds ratios (ORs) with 95% confidence
intervals (CIs) were extracted and pooled to assess the strength of the association between the LSP1 rs3817198T>C polymorphism
and risk of breast cancer. A total of seven eligible studies including 33,920 cases and 35,671 controls based on the search
criteria were involved in this meta-analysis. The distributions of genotypes in the controls were all in agreement with Hardy–Weinberg
equilibrium. We observed that the LSP1 rs3817198T>C polymorphism was significantly correlated with breast cancer risk when
all studies were pooled into the meta-analysis (the allele contrast model: OR = 1.06, 95% CI = 1.04–1.08; the homozygote codominant:
OR = 1.14, 95% CI = 1.01–1.28). In the stratified analysis by ethnicity, significant association was observed in Caucasians
for CC versus TT homozygote codominant model (OR = 1.25; 95% CI = 1.03–1.52) and for the recessive model (OR = 1.22; 95% CI = 1.02–1.47).
There was significant association observed in Africans for CC versus TT homozygote codominant model (OR = 0.45; 95% CI = 0.22–0.92)
and for the recessive model (OR = 0.43; 95% CI=0.22–0.88). Also, significant association was observed in mixed ethnicities
for CC versus TT homozygote codominant model (OR = 1.12; 95% CI = 1.05–1.19). When stratified by study design, statistically
significantly elevated risk was found in nested case–control studies (CC vs. TT: OR = 1.12, 95% CI = 1.05–1.19). But no significant
association was observed for all comparison models between LSP1 rs3817198T>C polymorphism and breast cancer risk in hospital-based
and people-based studies. When stratified by BRCA1 mutation carriers status, statistically significantly elevated risk was
found in this meta-analysis (the allele contrast model: OR = 1.07, 95% CI = 1.01–1.14; the dominant model: OR = 1.09, 95%
CI = 1.00–1.18). And significant association was found in the BRCA2 mutation carriers in the allele contrast (OR = 1.11, 95%
CI = 1.03–1.20), the homozygote codominant (OR = 1.23, 95% CI = 1.04–1.47), the heterozygote codominant (OR = 1.12, 95% CI = 1.00–1.25)
and the dominant models (OR = 1.14, 95% CI = 1.03–1.27). There was significant association between LSP1 rs3817198T>C polymorphism
and breast cancer risk in BRCA1 and BRCA2 positive cohort in all comparison models (the allele contrast model: OR = 1.08,
95% CI = 1.03–1.13; CC vs. TT: OR = 1.16, 95% CI = 1.05–1.29; TC vs. TT: OR = 1.09, 95% CI = 1.01–1.16; the dominant model:
OR = 1.10, 95% CI = 1.03–1.17; the recessive model: OR = 1.12, 95% CI = 1.01–1.23). In conclusion, this meta-analysis suggests
that the LSP1 rs3817198T>C polymorphism is a low-penetrant risk factor for developing breast cancer but may not be in Africans. 相似文献