Single-cell RNA-seq reveals MIF-(CD74 + CXCR4) dependent inhibition of macrophages in metastatic papillary thyroid carcinoma.

BACKGROUND: The mechanism promoting papillary thyroid carcinoma (PTC) metastasis remains unclear. We aimed to investigate the potential metastatic mechanisms at a single-cell resolution. METHODS: We performed single-cell RNA-seq (scRNA-seq) profiling of thyroid tumour (TT), adjacent normal thyroid (NT) and lymph node metastasized tumour (LN) from a young female with PTC. Validation of our results was conducted in 31 tumours with metastasis and 30 without metastasis. RESULTS: ScRNA-seq analysis generated data on 38,215 genes and 0.14 billion transcripts from 28,839 cells, classified into 18 clusters, each annotated to represent 10 cell types. PTC cells were found to originate from epithelial cells. Epithelial cells and macrophages emerged as the strongest signal emitters and receivers, respectively. After reclustering epithelial cells and macrophages, our analysis, incorporating gene set variation analysis (GSVA), SCENIC analysis, and pseudotime trajectory analysis, indicated that subcluster 0 of epithelial cells (EP_0) showed a more malignant phenotype, and subclusters 3 and 4 of macrophages (M_3 and M_4) demonstrated heightened activity. Further analysis suggested that EP_0 may suppress the activity of M_3 and M_4 via MIF - (CD74 + CXCR4) in the MIF pathway. After analysing the expression of the 4 genes in the MIF pathway in both the TCGA cohort and our cohort (n = 61), CD74 was identified as significantly overexpressed in PTC tumours particularly those with lymph node metastasis. CONCLUSION: Our study revealed that PTC may facilitate lymph node metastasis by inhibiting macrophages via MIF signalling. It is suggested that malignant PTC cells may suppress the immune activity of macrophages by consistently releasing signals to them via MIF-(CD74 + CXCR4).

C-IGF1R encoded by cIGF1R acts as a molecular switch to restrict mitophagy of drug-tolerant persister tumour cells in non-small cell lung cancer.

The clinical efficacy of Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors (EGFR-TKIs) is limited by the emergence of drug resistance. We hypothesise that restoring dysregulated circular RNAs under initial treatment with EGFR-TKIs may enhance their effectiveness. Through high-throughput screening, we identify that combining circular RNA IGF1R (cIGF1R) with EGFR-TKIs significantly synergises to suppress tumour regrowth following drug withdrawal. Mechanistically, cIGF1R interacts with RNA helicase A (RHA) to depress insulin-like growth factor 1 receptor (IGF1R) mRNA splicing, negatively regulating the parent IGF1R signalling pathway. This regulation is similar to that of IGF1R inhibitor, which induces drug-tolerant persister (DTP) state with activated mitophagy. The cIGF1R also encodes a peptide C-IGF1R that reduces Parkin-mediated ubiquitination of voltage-dependent anion channel 1 (VDAC1) to restrict mitophagy, acting as a molecular switch that promotes the transition of DTP to apoptosis. Our study shows that combining cIGF1R with EGFR-TKIs efficiently reduces the emergence of DTP.

The super-enhancer-driven lncRNA LINC00880 acts as a scaffold between CDK1 and PRDX1 to sustain the malignance of lung adenocarcinoma.

Super-enhancers (SEs) are regulatory element clusters related to cell identity and disease. While the studies illustrating the function of SE-associated long noncoding RNAs (lncRNAs) in lung adenocarcinoma (LUAD) remains few. In our research, a SE-driven lncRNA, LINC00880, was identified, which showed higher expression in LUAD compared to normal tissues and indicated worse outcomes in stage I LUADs. We found that the transcription factor (TF) FOXP3 could simultaneously occupy the promoter and SE regions of LINC00880 to promote its transcription. The oncogenic function of LINC00880 was validated both in vitro and in vivo. Mechanically, LINC00880 binds to the protein CDK1 to increase its kinase activity, which rely on the phosphorylation state of pT161 in CDK1. LINC00880 also promotes the interaction between CDK1 and PRDX1. Moreover, LINC00880 interacts with PRDX1, which indicates that LINC00880 acts as a protein scaffold between CDK1 and PRDX1 to form a ternary complex, thereby resulting in the activation of PI3K/AKT to promote malignancy. Our results reveal that the SE-associated lncRNA LINC00880 regulates the CDK1/PRDX1 axis to sustain the malignancy of LUAD, providing a novel therapeutic target.

Tobacco exposure primes the secretion of CCL21 positively associated with tertiary lymphoid structure and response to immunotherapy.

BACKGROUND: It has been reported that smoking history as a predictor of immunotherapy efficacy in patients with advanced lung cancer, however, the underlying mechanisms of this phenomenon remain largely unknown. METHODS: The patients with lung adenocarcinoma's (LUAD) cohort and the orthotopical transplanted mouse model were used to explore the correlation between smoking status and tertiary lymphoid structure (TLS) and chemokine CCL21, respectively. Cell adhesion and co-immunoprecipitation assays were performed to explore the interaction between CD4+T cells and CD20+B cells under tobacco exposure. Chromatin immunoprecipitation-PCR was used to dissect the mechanism of upregulated CCL21 secretion in tobacco treatment. Serum CCL21 level was recorded in patients with LUAD treated with immunotherapy. RESULTS: Here we observed that individuals with a smoking history exhibit an increased quantity and maturation level of TLS compared with non-smokers, along with higher levels of CCL21 secretion. Tobacco exposure promoted CCL21 expression in an epithelial cell-intrinsic manner, of which BaP, the main component of tobacco, facilitated the nuclear retention of the aryl hydrocarbon receptor that occupied the promoter of CCL21. Additionally, the activated CCL21/CCR7 axis increased the CD11a expression of CD4+T cells, boosting the interaction with CD20+B cells dependent on ICAM1, which potentially induced the TLSs formation. Patients with elevated serum levels of CCL21 benefited more from immunotherapy. CONCLUSIONS: Patients with a smoking history exhibited higher levels of TLS via the CCL21-dependent mechanism, serum CCL21 was identified as a reliable biomarker for predicting the efficacy of immunotherapy.

Integrating single-cell RNA-seq and spatial transcriptomics reveals MDK-NCL dependent immunosuppressive environment in endometrial carcinoma.

Objectives: The tumor microenvironment (TME) play important roles in progression of endometrial carcinoma (EC). We aimed to assess the cell populations in TME of EC. Methods: We downloaded datasets of single-cell RNA-seq (scRNA-seq) and spatial transcriptome (ST) for EC from GEO, and downloaded RNA-Seq (FPKM) and clinical data of TCGA-UCEC project from TCGA. The datasets were analyzed using R software. Results: We obtained 5 datasets of scRNA-seq, 1 of ST and 569 samples of RNA-seq. Totally, 0.2 billion transcripts and 33,408 genes were detected in 33,162 cells from scRNA-seq. The cells were classified into 9 clusters, and EC cells were originated from epithelial cells and ciliated cells. Gene set variation analysis (GSVA) indicated that the pathways enriched in the subclusters of epithelial cells and endothelial cells were significantly different, indicating great heterogeneity in EC. Cell-cell communication analyses showed that EC cells emitted the strongest signals, and endothelial cells received more signals than other cells. Further analysis found that subclusters of 1 and 2 of epithelial cells were showed a more malignant phenotype, which may confer malignant phenotype to subcluster of 0 of endothelial cells through MK pathway by MDL-NCL signal. We also analyzed communications between spatial neighbors with ST data and confirmed the findings on MDL-NCL in cell-cell communication. TCGA and GEO analyses indicated that the expression levels of NCL was inversely correlated with ImmuneScore. Conclusion: Our study revealed EC cells can confer malignant phenotype to endothelial cells by MDK-NCL signal, and NCL is associated with suppressed immune activity. EC cells may shape TME by inhibiting immune cells and "educating" stromal cells via MDK-NCL signal.

Super-enhancer hijacking LINC01977 promotes malignancy of early-stage lung adenocarcinoma addicted to the canonical TGF-ß/SMAD3 pathway.

BACKGROUND: Lung adenocarcinoma (LUAD) is the leading cause of death worldwide. However, the roles of long noncoding RNAs (lncRNAs) hijacked by super-enhancers (SEs), vital regulatory elements of the epigenome, remain elusive in the progression of LUAD metastasis. METHODS: SE-associated lncRNA microarrays were used to identify the dysregulated lncRNAs in LUAD. ChIP-seq, Hi-C data analysis, and luciferase reporter assays were utilized to confirm the hijacking of LINC01977 by SE. The functions and mechanisms of LINC01977 in LUAD were explored by a series of in vitro and in vivo assays. RESULTS: We found that LINC01977, a cancer-testis lncRNA, was hijacked by SE, which promoted proliferation and invasion both in vitro and in vivo. LINC01977 interacted with SMAD3 to induce its nuclear transport, which facilitated the interaction between SMAD3 and CBP/P300, thereby regulating the downstream target gene ZEB1. Additionally, SMAD3 up-regulated LINC09177 transcription by simultaneously binding the promoter and SE, which was induced by the infiltration of M2-like tumor-associated macrophages (TAM2), subsequently activating the TGF-ß/SMAD3 pathway. Moreover, LINC01977 expression was positively correlated with TAM2 infiltration and SMAD3 expression, especially in early-stage LUAD. Higher chromatin accessibility in the SE region of LINC01977 was observed with high expression of TGF-ß. Early-stage LUAD patients with high LIN01977 expression had a shorter disease-free survival. CONCLUSIONS: TAM2 infiltration induced a rich TGF-ß microenvironment, activating SMAD3 to bind the promoter and the SE of LINC01977, which up-regulated LINC01977 expression. LINC01977 also promoted malignancy via the canonical TGF-ß/SMAD3 pathway. LINC01977 hijacked by SE could be a valuable therapeutic target, especially for the treatment of early-stage LUAD.

Comparison of Two Approaches to Enhance Self-Esteem and Self-Acceptance in Chinese College Students: Psychoeducational Lecture vs. Group Intervention.

Objective: Self-esteem and self-acceptance are not only basic features but also influential factors of mental health. The present study aimed at assessing the effects of psychoeducational lecture and group intervention on self-esteem and self-acceptance in Chinese college students. Methods: A total of 149 Chinese college students who participated in a mental health course were randomly class-based assigned into the psychoeducational lecture group (n = 62) and the self-focused intervention group (n = 87). The lecture group received 6-session psychoeducational lectures on overview of mental health, campus adaptation, stress adjustment, self-understanding, emotion management, and interpersonal relationships. The self-focused intervention group was treated with self-related group activities involving aspects of self-knowledge, self-feeling, and self-regulation for six sessions. Pre- and post-intervention measurements were taken with Rosenberg Self-Esteem Scale and Self-Acceptance Questionnaire for both groups. Results: Self-esteem significantly increased in both groups after six sessions. However, the enhancement of self-acceptance was more robust for the self-focused intervention group than the psychoeducational lecture group. Conclusion: The psychoeducational lecture and self-focused intervention were effective approaches to improve self-esteem for Chinese college students. With respect to self-acceptance, self-focused group intervention might have a more prominent effect.

tRF-20-S998LO9D inhibits endometrial carcinoma by upregulating SESN2.

Aim: To explore the roles of transfer RNA-derived small RNAs (tsRNAs) in endometrial carcinoma (EC). Materials & methods: tsRNA profiles for EC from TCGA were analyzed. The functions and mechanisms of tsRNA were explored using in vitro experiments. Results: 173 dysregulated tsRNAs were identified. After validating in EC tissues and serumal exosome samples from EC patients, a downregulated tsRNA in both EC tissues and serumal exosomes (i.e., tRF-20-S998LO9D) was observed. Exosomal tRF-20-S998LO9D had an area under the curve of 0.768. tRF-20-S998LO9D overexpression inhibited proliferation, migration and invasion and promoted apoptosis of EC cells and tRF-20-S998LO9D knockdown further confirmed its effects. Further analyses showed that tRF-20-S998LO9D upregulated SESN2 in protein levels. Conclusion: tRF-20-S998LO9D inhibits EC cells by upregulating SESN2.

Long noncoding RNA MACC1-AS1 promotes the stemness of nonsmall cell lung cancer cells through promoting UPF1-mediated destabilization of LATS1/2.

The roles of long noncoding RNA (lncRNA) MACC1-AS1 have been revealed in various tumors. This work aims to explore the roles of lncRNA MACC1-AS1 in the stemness of nonsmall cell lung cancer (NSCLC) cells and the underlying mechanism. We showed that overexpression of MACC1-AS1 enhanced the stemness of NSCLC cells, which is evident as the increased expression of cancer stem cell transcription factors, ALDH1 activity, and sphere-formation capacity, while knockdown of MACC1-AS1 decreased it. RNA-sequencing analysis revealed that the Hippo pathway was mostly enriched in NSCLC cell with MACC1-AS1 overexpression. Further mRNA and western blot analysis showed that ectopic expression of MACC1-AS1 regulated the expression LATS1/2, the critical regulator of Hippo pathway. Additionally, it was found that MACC1-AS1 interacted with up-frameshift 1 (UPF1) to modulate mRNA decay of LATS1/2. Overexpression of LAST1/2 attenuated the promoting effects of MACC1-AS1 overexpression on the stemness of NSCLC cells. Therefore, our results demonstrate the effects of the novel MACC1-AS1/UPF1/LATS1/2 axis in NSCLC cell stemness.

Pre-miR-27a rs895819 polymorphism and risk of diffuse large B-cell lymphoma.

BACKGROUND: Recently, several studies have investigated the relationship between Pre-miR-27a rs895819 polymorphism and risk of various cancers. However, the relationship between rs895819 and diffuse large B-cell lymphoma (DLBCL) has not been well known. METHODS: In this study, we conducted a case-control study to explore the role of Pre-miR-27a rs895819 in risk of DLBCL. The PCR-TaqMan and luciferase assays and in vitro experiments were used to evaluate polymorphism function. RESULTS: As a result, we found subjects carrying with rs895819 AG/GG genotype had a significantly decreased risk when compared with those carrying the AA genotype. Further qPCR assay showed that the DLBCL patients carrying AG/GG genotypes showed a lower level of mature miR-27a when compared with patients carrying AA genotype. Moreover, miR-27a levels were upregulated in DLBCL tissues compared with normal lymphoid tissues. Further in vitro experiments showed that miR-27a might function as an oncogene through target TGFBR1. In addition, TGFBR1 overexpression rescues effects of miR-27a inhibitor on DLBCL cells phenotypes. CONCLUSIONS: In conclusion, these findings indicate that rs895819 A > G might reduce the expression of mature miR-27a, and leading a higher level of TGFBR1, ultimately inhibiting the development of DLBCL.

Identification of internal control genes for circular RNAs.

OBJECTIVE: At present, no studies have established internal control genes for circular RNA (circRNA) analyses. We aimed to identify reference circRNAs for real-time quantitative PCR (RT-qPCR). RESULTS: After analyzing the RNA-seq data, we obtained 50 circRNAs that were expressed in all samples. We ranked these 50 circRNAs according to their stability and obtained the six most stable circRNAs. We further evaluated the stability of the six circRNAs and three linear control genes (i.e., GAPDH, ß-actin and 18S rRNA) in 22 cell lines. Our results indicated that hsa_circ_0000284 (circHIPK3) and hsa_circ_0000471 (circN4BP2L2) were the two most stable genes. After removing linear RNAs or including the cells treated with Adriamycin, NH4Cl and shikonin, the two most stable genes were hsa_circ_0000471 and hsa_circ_0000284. The amplification efficiency was 100% for hsa_circ_0000471 and 95% for hsa_circ_0000284. CONCLUSIONS: In conclusion, since the stability of circRNAs is higher than that of linear RNAs, hsa_circ_0000284 and hsa_circ_0000471 may be used as reference genes not only for circRNAs but also for other kinds of RNAs. The findings in the present study fill the gap of lacking reference genes in the detection of circRNAs.

Lymph node metastasis in Chinese patients with clinical T1 non-small cell lung cancer: A multicenter real-world observational study.

BACKGROUND: Approximately 8.3-15.9% of patients with clinical stage I non-small cell lung cancer are subsequently shown to have lymph node metastasis. However, the clinical characteristics of patients with lymph node metastasis in China are not fully understood. METHODS: This is a multicenter retrospective analysis of pathological T1 non-small cell lung cancer patients who underwent surgical resection from 2 January 2014 to 27 December 2017. Clinical and pathological information was collected with the assistance of the Large-scale Data Analysis Center of Cancer Precision Medicine-LinkDoc database. The clinical and pathological factors associated with lymph node metastasis were analyzed by univariate and multivariate logistic regression. RESULTS: A total of 10 885 participants (51.6% women; 15.3% squamous cell carcinoma) were included in the analysis. The median age was 60.0 years (range 12.9-86.6 years). A total of 1159 patients (10.6%) had metastases in mediastinal nodes (N2), and 640 patients (5.9%) had metastasis in pulmonary lymph nodes (N1). Most patients had T1b lung cancer (4766, 43.8%). Of the patients, 3260 (29.9%) were current or former smokers. The univariate and multivariate analyses showed that younger age, squamous cell carcinoma, poor differentiation, larger tumor size, carcinoembryonic antigen level ≥5 ng/mL, and vascular invasion (+) were significantly associated with higher percentages of lymph node metastases (P < 0.001 for all). CONCLUSION: This real-world study showed the significant association of lymph node metastasis with age, tumor size, histology and differentiation, carcinoembryonic antigen levels, and status of vascular invasion. Female patients with T1a adenocarcinoma in the right upper lobe barely had lymph node metastasis.

Improvement of survival for non-small cell lung cancer over time.

Non-small cell lung cancer (NSCLC) is the main histological subtype of lung cancer, which is the leading cause of cancer death. It is unclear whether the improved survival seen at high-volume centers applies to the general population and, more importantly, whether the improvement in lung cancer survival was just a consequence of improved screening work. Data from the Surveillance, Epidemiology, and End Results (SEER) registry was used to identify 405,580 patients with NSCLC diagnosed from 1988 to 2008. The patients were divided into four groups according to the year of diagnosis. Trends of clinical characteristics were analyzed to reflect the progress of screening work. Five-year relative survivals in various subgroups were compared. The results indicated that proportion of aged, advanced, and non-surgical patients increased, whereas patients with lymph node metastasis and high histology grade decreased. Improvements in all stages of NSCLC patients were demonstrated, with relatively more significant gains for patients with localized and regional disease. After potentially curative surgical resection, remarkable improvements were observed in both cohorts with time (surgical: 52.00%-63.00%; non-surgical: 6.10%-13.50%). Specifically, patients who underwent pneumonectomy, lobectomy/bilobectomy, and partial/wedge/segmental resection all presented better survival rates. Our SEER analysis demonstrated improvements among patients in all stages of NSCLC that were deemed attributable to improved therapy and medical care for NSCLC rather than improved screening work.

Hormone replacement therapy and breast cancer survival: a systematic review and meta-analysis of observational studies.

Previous studies on the association between hormone replacement therapy (HRT) and breast cancer survival have yielded mixed results. We aimed to perform a meta-analysis to assess the association with all available studies. Relevant studies were identified by searching PubMed and EMBASE to April 2017. We calculated the summary hazard ratios (HRs) and 95% confidence intervals (CIs) using random-effects models. The dose-response relationship was assessed by random-effects meta-analysis and dose-response meta-regression models. Forty cohort studies and two case-control studies involving 1,756,833 participants were included. The results showed that prediagnosis HRT use was associated with decreased risk of dying from breast cancer (HR = 0.88, 95% CI 0.81-0.97) or any cause (HR = 0.79, 95% CI 0.69-0.90). Postdiagnosis HRT use also showed a beneficial effect on breast cancer survival. In the subgroup analyses, we found that patients who were current users at diagnosis or who received combined hormone therapy before diagnosis seemed to show more benefit from HRT use. In dose-response analysis, we observed a linear relationship between prediagnosis HRT and breast cancer-specific mortality and a 1-year increment in duration of exposure to HRT conferred an HR of 0.99 (95% CI 0.98-1.00) for death from breast cancer. In conclusion, the average effect of HRT use seems not harmful to breast cancer survival. Nevertheless, this effect of HRT use is needed for further assessment.

Expression profile, clinical significance, and biological function of insulin-like growth factor 2 messenger RNA-binding proteins in non-small cell lung cancer.

Insulin-like growth factor 2 messenger RNA-binding proteins have been described to associate with malignant process in many cancers. However, the role of insulin-like growth factor 2 messenger RNA-binding protein family has not been thoroughly elucidated in non-small cell lung cancer. This study was to investigate the expression profile, clinical significance, and biological function of insulin-like growth factor 2 messenger RNA-binding proteins family in non-small cell lung cancer. The expression levels of IGF2BP1-IGF2BP3 in tumor and adjacent normal tissues were determined, and association with clinicopathological features and overall survival was investigated by analyzing The Cancer Genome Atlas lung cancer database. Proliferation, migration, invasion assays, and flow-cytometry analysis were used to investigate the biological function in vitro. Insulin-like growth factor 2 messenger RNA-binding protein expression levels were significantly increased in non-small cell lung cancer compared to adjacent normal lung tissues. Chi-square test indicated that IGF2BP1 and IGF2BP3 expressions correlated with some meaningful clinical characteristics in non-small cell lung cancer. Kaplan-Meier analysis showed that high-level expression of IGF2BP1 or IGF2BP3 predicted poor overall survival in lung adenocarcinoma patients. Multivariate regression analysis showed that high level of IGF2BP3 was an independent risk factor for poor prognosis in lung adenocarcinoma patients (hazard ratio = 1.616, p = 0.017). In vitro, knockdown of IGF2BP3 inhibited lung adenocarcinoma cell proliferation by inducing cell cycle arrest and apoptosis, and undermined abilities of migration and invasion, and overexpression of IGF2BP3 could promote malignant phenotypes in lung adenocarcinoma cells. Our study revealed that expression of insulin-like growth factor 2 messenger RNA-binding proteins was widely upregulated and correlated with some certain clinicopathological features in non-small cell lung cancer. Especially, in insulin-like growth factor 2 messenger RNA-binding protein family, IGF2BP3 might play the most important role in tumor aggressiveness and prognosis in lung adenocarcinoma, and IGF2BP3 might serve as a potential therapeutic target and a novel prognostic biomarker in lung adenocarcinoma patients.

Rumination mediates the relationship between overgeneral autobiographical memory and depression in patients with major depressive disorder.

BACKGROUND: Overgeneral autobiographical memory has been identified as a risk factor for the onset and maintenance of depression. However, little is known about the underlying mechanisms that might explain overgeneral autobiographical memory phenomenon in depression. The purpose of this study was to test the mediation effects of rumination on the relationship between overgeneral autobiographical memory and depressive symptoms. Specifically, the mediation effects of brooding and reflection subtypes of rumination were examined in patients with major depressive disorder. METHODS: Eighty-seven patients with major depressive disorder completed the 17-item Hamilton Depression Rating Scale, Ruminative Response Scale, and Autobiographical Memory Test. Bootstrap mediation analysis for simple and multiple mediation models through the PROCESS macro was applied. RESULTS: Simple mediation analysis showed that rumination significantly mediated the relationship between overgeneral autobiographical memory and depression symptoms. Multiple mediation analyses showed that brooding, but not reflection, significantly mediated the relationship between overgeneral autobiographical memory and depression symptoms. CONCLUSIONS: Our results indicate that global rumination partly mediates the relationship between overgeneral autobiographical memory and depressive symptoms in patients with major depressive disorder. Furthermore, the present results suggest that the mediating role of rumination in the relationship between overgeneral autobiographical memory and depression is mainly due to the maladaptive brooding subtype of rumination.

The interleukin-10-1082A>G polymorphism and lymphoma risk: a meta-analysis.

OBJECTIVE: The Interleukin-10 (IL-10) gene polymorphism (-1082 A>G) has been linked to the risk of developing lymphoma, but the available results were inconsistent. To derive a more precise estimation, we performed a meta-analysis. METHODS: A comprehensive search was conducted to examine all the eligible studies about IL-10-1082A>G polymorphism and lymphoma risk. We used odds ratios (ORs) with 95% confidence intervals (CIs) to assess the strength of the association. RESULTS: We included 12 studies, including 5847 cases and 6016 controls. The overall results suggested that the IL-10-1082G allele was associated with a borderline significantly increased risk of lymphoma (G vs. A: OR=1.07, 95% CI=1.01-1.12; GG vs. AA: OR=1.14, 95% CI=1.02-1.26; and AG+GG vs. AA: OR=1.10, 95% CI=1.02-1.19). Stratifying by ethnicity (Caucasian and mixed), tumor type [non-Hodgkin lymphoma (NHL) and Hodgkin lymphoma (HL)], sample size (> 1000 and ⩽ 1000 subjects) and Hardy-Weinberg equilibrium (HWE) in controls, similar results were found in mixed subgroup, NHL subgroup, large studies and the subgroup conforming to HWE. CONCLUSIONS: In conclusion, the meta-analysis suggests that the IL-10-1082A>G polymorphism is weakly associated with altered susceptibility to lymphoma. Further studies with haplotype analysis and on larger population of mixed ethnicity are warranted for a more definitive conclusion.

A meta-analysis of genotypes and haplotypes of methylenetetrahydrofolate reductase gene polymorphisms in breast cancer.

The association between methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms and breast cancer risk has been extensively explored, but their results are conflicting rather than conclusive. To derive a more precise estimation, we carried out not only an updated meta-analysis but also a combined analysis based on all the available studies estimating the association between MTHFR C677T and/or A1298C and breast cancer risk. With respect to C677T polymorphism, the results suggested that 677T allele was associated with significantly elevated breast cancer risk in overall analysis (T vs. C: OR 1.073, 95 % CI 1.028-1.120; TT vs. CC: OR 1.177, 95 % CI 1.072-1.293; TT vs. CC + CT: OR 1.175, 95 % CI 1.073-1.288); Stratifying by ethnicity, significantly increased risk was only found in East Asians (T vs. C: OR 1.150, 95 % CI 1.039-1.273; TT vs. CC: OR 1.441, 95 % CI 1.145-1.814; TT vs. CC + CT: OR 1.413, 95 % CI 1.148-1.739); When stratified by menopausal status, statistically significant association was found for postmenopausal women (CT + TT vs. CC: OR 1.092, 95 % CI 1.011-1.179). In regard to A1298C polymorphism, no significant associations were found between the polymorphism and breast cancer risk. With respect to MTHFR haplotypes, significantly elevated breast cancer risk was associated with 677T-1298C for overall result (OR 1.498, 95 % CI 1.143-1.962) and for Caucasians (OR 2.088, 95 % CI 1.277-3.416) when compared with 677C-1298A; Haplotype 677C-1298C might provide higher protection than 677C-1298A in East Asians (OR 0.840, 95 % CI 0.742-0.949). The combined genotypes for C677T and A1298C produced a significant OR for the 677TT/1298AC relative to 677CC/1298AA in overall population (OR 2.047, 95 % CI 1.275-3.288); When stratified by ethnicity, significant ORs were only found for East Asians (677CC/1298CC vs. 677CC/1298AA: OR 0.686, 95 % CI 0.478-0.985; 677TT/1298AC vs. 677CC/1298AA: OR 2.181, 95 % CI 1.179-4.035). The findings suggest that the MTHFR C677T polymorphism but not A1298C, and some variants on their combined genotypes or haplotypes may be involved with the development of breast cancer.

Tea consumption and leukemia risk: a meta-analysis.

Epidemiologic findings concerning the association between tea consumption and leukemia risk yielded mixed results. We aimed to investigate the association by performing a meta-analysis of all available studies. One cohort studies and six case-control studies with 1,019 cases were identified using PubMed, Web of Science, and EMBASE. We computed summary relative risks (RRs) and 95 % confidence intervals (CIs) using random effect model applied to the relative risk associated with ever, moderate, or highest drinkers vs. non/lowest drinkers. Subgroup analyses were performed based on country (China and USA). Compared with non/lowest drinkers, the combined RR for ever drinkers was 0.76 (95 % CI=0.65-0.89). In subgroup analyses, significant inverse associations were found for both China and USA studies. The summary RR was 0.57 (95 % CI=0.41-0.78) for highest drinkers. Same results were only found in China studies. No significant associations were found for moderate drinkers in overall analysis or in subgroup analyses. There was some evidence of publication bias. In conclusion, this meta-analysis suggests a significant inverse association of high tea consumption and leukemia risk. Results should be interpreted cautiously given the potential publication bias.

[Progress of microRNA in diagnosis and prognosis of diffuse large B cell lymphoma-review].

MicroRNA (miRNA) is a class of naturally occurring short non-coding small molecular RNA with 19-25 nucleotide. MiRNA can regulate gene expression through incompletely binding to complementary sequences in the 3'UTR of target mRNA. MiRNA plays key regulatory role in a diverse rang of pathways, including cell proliferation, differentiation, apoptosis, stem cell development. Many studies have shown that many miRNA have a special role of gene regulation in cancer development and have been used as therapeutic targets and diagnostic markers of cancer. This review focuses on recent advances of studies on miRNA involved in tumorigenesis, and in classification, diagnosis, therapy and prognosis of DLBCL.