Retrospective analysis of the 18F-FDG PET/CT cutoff value for metabolic parameters was performed as a prediction model to evaluate risk factors for endometrial cancer.

PURPOSE: The study retrospectively analyzed the accuracy and predictive ability of preoperative integrated whole-body 18F-FDG PET/CT for the assessment of high-risk factors in patients with endometrial carcinoma (EC). MATERIALS AND METHODS: A total of 205 patients with endometrial cancer who underwent preoperative PET/CT at Shanghai General Hospital from January 2018 to December 2021 were retrospectively evaluated and last follow-up was June 2023. Our study evaluated the ability and optimal cutoff values of three metabolic and volumetric parameters-standardized uptake value (SUV), metabolic tumor volume (MTV) and total lesion glycolysis (TLG)-to predict deep myometrial invasion (DMI), endocervical stroma invasion (ESI) and lymph node metastases (LNM) in endometrial cancer. The accuracy, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of PET/CT were used to assess the diagnostic performance for the prediction. RESULTS: Our study demonstrated a significant relationship between SUVmax (11.29, 17.38, 9.47), SUVmean (5.20, 6.12, 4.49), MTV (38.15, 36.28, 33.79 ml), and TLG (199.30, 225.10, 156.40 g) on PET/CT and histologically confirmed DMI, ESI and LNM in endometrial carcinoma (EC), with sensitivity, specificity, accuracy, PPV, and NPV of 100%/100%/100%, 96.53%/98.89%/87.14%, 97.56%/99.02%/91.22%, 92.42%/92.85%/78.31%, and 100%/100%/100%, respectively. Our study showed a risk model based on optimal cutoff values for MTV and TLG of 19.6 ml/126.3 g, 20.54 ml/84.80 g and 24 ml/49.83 g to preoperatively predict DMI, ESI, and LNM, respectively, in endometrial carcinoma. The 4-year OS (HR) for Stage IA, IB, II, III and IV according to 2009 FIGO was 98.00% (0.22), 95.20% (0.04), 83.90% (0.18), 90.50% (0.09) and 60% (0.51). Accordingly, estimated 4-year DFS (HR) for the stage IA-III was 98% (0.02), 95.20% (0.05), 76.90% (0.27) and 76.30% (0.35), all the patients in stage IV occurred recurrence and progression. CONCLUSION: The present study showed patients with MTV > = 19.6 ml of MI and PET- positive LN with MTV cutoff > = 24 ml tended to predict poor OS and PFS in endometrial carcinoma. The cutoff of MTV and TLG in PET/CT assessment could be an independent prognostic factors to predict aggressive forms of EC.

Ergonomic learning curves on gynecological laparoendoscopic single-site (LESS) surgery.

BACKGROUND: Few previous studies have introduced general techniques to overcome the "chopstick effect" in laparoendoscopic single-site surgery (LESS). We aim to investigate and highlight the key ergonomic methodologies for gynaecologic LESS based on the surgeon's hands-on performance. METHODS: The first author surgeon A reviewed and analyzed the LESS procedures performed by herself and how she taught surgeon B from January 2021 to April 2022. The procedures were classified based on technical difficulty and learning periods, and the hands-on technical skills of LESS module were evaluated. RESULTS: Surgeon A conducted 580 LESS procedures, which were divided into the novice (n = 48) and intermediate (n = 33) periods, and the remaining cases were included in the routine period. We formed a special ergonomic LESS operating methodology: Maintain good LESS laparoscopic spatial sensation, keep hand-eye coordination, well cooperation between the main surgeon and the assistant; Experienced multiport laparoscopy surgery (MPS) skills, improve basic LESS technique: grasp, lift, transfer, place, blunt separating, coagulation and cutting. Coordination location, orientation, movements, and flexion or extension of shoulders, arms, elbow, wrist and finger joints; Maintain strength, tension and ambidexterity postures with joint and muscular efforts to control instruments. Surgeon B learned the above experiences by performing 39 LESS procedures under the guidance of surgeon A. CONCLUSION: This educational research sheds light on the common challenges faced in LESS and presents the importance of ergonomic hands-on performance skills in improving surgical outcomes, which could serve as a guide for future training and education in LESS.

The role of Vps4 in cancer development.

VPS4 series proteins play a crucial role in the endosomal sorting complexes required for the transport (ESCRT) pathway, which is responsible for sorting and trafficking cellular proteins and is involved in various cellular processes, including cytokinesis, membrane repair, and viral budding. VPS4 proteins are ATPases that mediate the final steps of membrane fission and protein sorting as part of the ESCRT machinery. They disassemble ESCRT-III filaments, which are vital for forming multivesicular bodies (MVBs) and the release of intraluminal vesicles (ILVs), ultimately leading to the sorting and degradation of various cellular proteins, including those involved in cancer development and progression. Recent studies have shown a potential relationship between VPS4 series proteins and cancer. Evidence suggests that these proteins may have crucial roles in cancer development and progression. Several experiments have explored the association between VPS4 and different types of cancer, including gastrointestinal and reproductive system tumors, providing insight into the underlying mechanisms. Understanding the structure and function of VPS4 series proteins is critical in assessing their potential role in cancer. The evidence supporting the involvement of VPS4 series proteins in cancer provides a promising avenue for future research and therapeutic development. However, further researches are necessary to fully understand the mechanisms underlying the relationship between VPS4 series proteins and cancer and to develop effective strategies for targeting these proteins in cancer therapy. This article aims to review the structures and functions of VPS4 series proteins and the previous experiments to analyze the relationship between VPS4 series proteins and cancer.

MiR-142-3p functions as a tumor suppressor by targeting RAC1/PAK1 pathway in breast cancer.

MicroRNA-142-3p (miR-142-3p) was previously investigated in various cancers, whereas, it's role in breast cancer (BC) remains far from understood. In this study, we found that miR-142-3p was markedly decreased both in cell lines and BC tumor tissues. Elevated miR-142-3p expression suppressed growth and metastasis of BC cell lines via gain-of-function assay in vitro and in vivo. Mechanistically, miR-142-3p could regulate the ras-related C3 botulinum toxin substrate 1 (RAC1) expression in protein level, which simultaneously suppressed the epithelial-to-mesenchymal transition related protein levels and the activity of PAK1 phosphorylation, respectively. In addition, rescue experiments revealed RAC1 overexpression could reverse tumor-suppressive role of miR-142-3p. Our results showed miR-142-3p could function as a tumor suppressor via targeting RAC1/PAK1 pathway in BC, suggesting a potent therapeutic target for BC treatment.

Expression of thyroglobulin by regulatory T cells in thyroid tissue.

The follicles are the minimal functional unit of the thyroid; the morphology and the function of each follicle can vary significantly. However, the reasons for the apparent follicular heterogeneity are poorly understood. Some tissue-resident regulatory T cells (Tregs) have a special phenotype that expresses unique molecules related to local tissue and regulates the tissue functions. The aim of this study was to identify the phenotype of thyroid Tregs and the roles of thyroid Tregs in thyroid physiological regulation. Thyroid tissue and peripheral blood samples were obtained from patients with benign thyroid nodules. Microarray-based gene expression, flow cytometry, immunofluorescence microscopy, and functional analysis of thyroid Tregs were performed. Here, we demonstrated that human thyroid Tregs expressed high level of thyroglobulin (Tg), both gene and protein. The immunofluorescence microscopy of thyroid section showed that the FOXP3+Tg+ cells concentrated in some of the thyroid follicles, at the side of the thyroid follicle. The peripheral blood Tregs expressed minimal levels of Tg, and low levels of Tg could effectively induce peripheral blood Tregs to express Tg, which was independent of thyrotropin simulation. Furthermore, the Tg secreted freely from thyroid Tregs that negatively regulated some thyroid-related genes expression. Our results revealed that the thyroid Tregs was a distinct population of Tregs, which expressed high level of Tg. The thyroid Tregs regulate thyroid function by Tg that is paracrine from the cells.

Identification of critically carcinogenesis-related genes in basal cell carcinoma.

BACKGROUND: Basal cell carcinoma (BCC) is a frequent malignant tumor of skin cancers with high morbidity. The objective of this study was to identify critical genes and pathways related to the carcinogenesis of BCC and gain more insights into the underlying molecular mechanisms of BCC. MATERIALS AND METHODS: The gene expression profiles of GSE7553 and GSE103439 were downloaded from the Gene Expression Omnibus database with 19 tumors and 6 normal skin tissues. Differentially expressed genes (DEGs) were screened between BCC samples and normal tissues, followed by gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis. Subsequently, protein-protein interaction (PPI) network was constructed for these DEGs, and module analysis was performed. RESULTS: A total of 313 DEGs were obtained. Among them, 222 genes were upregulated and 91 genes were downregulated. Enrichment analysis indicated that the upregulated genes were significantly enriched in cell cycle and mitosis, while the downregulated genes were mainly associated with unsaturated fatty acid metabolic process and cell differentiation. In addition, TOP2A, CDK1, and CCNB1 were identified as the top three hub genes ranked by degrees in the PPI network. Meanwhile, three subnetworks were derived, which indicated that these DEGs were significantly enriched in pathways, including "cell cycle", "extracellular matrix-receptor interaction", "basal cell carcinoma", and "hedgehog signaling pathway". CONCLUSIONS: The novel critical DEGs and pathways identified in this study may serve pivotal roles in the carcinogenesis of BCC and indicate more molecular targets for the treatment of BCC.

microRNA-485-5p Functions as a Tumor Suppressor in Colorectal Cancer Cells by Targeting CD147.

Colorectal cancer(CRC) is a prevalent malignancy in the world. There is growing evidence that microRNAs (miRNAs) as crucial modulator are in connection with many tumor-related diseases including CRC. Though miR-485-5p has been reported as an anti-oncogene in certain cancers, it remains unclear in CRC. In this research, we found that miR-485-5p was at lower level expression in CRC tissues and cell lines compared to the paired paracancerous tissues and the normal colon epithelial cell line FHC, correspondingly. Furthermore, Experimental up-regulation miR-485-5p in DLD-1 and SW480 cells with mimic could inhibit the ability of proliferation, migration, invasion of CRC cell lines and facilitate cells apoptosis. Also, we confirmed that CD147 existed typically negative regulation by miR-485-5p through binding a conserved sequence specifically within the CD147 3'-untranslated region (3'UTR) and reintroduction of CD147 could rescue the phenotypic changes caused by miR-485-5p. The findings provide evidence to demonstrate the role of miR-485-5p/CD147 interaction in CRC and indicate that miR-485-5p might be exploited therapeutically in CRC.

Fibroblast Growth Factor 2 Modulates Hippocampal Microglia Activation in a Neuroinflammation Induced Model of Depression.

Recent studies indicate that disturbed structure and function of microglia can cause depression and associated neurogenesis impairments. Our previous work has demonstrated that exogenous fibroblast growth factor 2 (FGF2) reverses the depressive-like behaviors and the impaired hippocampal neurogenesis in a neuroinflammatory model of depression. However, whether and how the antidepressant effects of FGF2 involve the modulation of microglia activation has not been elucidated. In this study, to examine the effects of FGF2 on microglia activation, exogenous FGF2 was supplemented to the lateral ventricle of rats during the neuroinflammatory state induced by central lipopolysaccharides (LPS) administrations. It was found that FGF2 infusions reversed the LPS-induced depressive-like behaviors and inhibited the hippocampal microglia activation. In LPS-treated rats, FGF2 decreased the level of pro-inflammatory cytokines including interlukin-1ß (IL-1ß), IL-6 and tumor necrosis factor (TNF)-α, increased the level of IL-10, the anti-inflammatory cytokine and reversed the decreased expression of CX3CL1, a chemokine mainly expressed by neurons and keeping microglia in surveillance. Further, we examined the effects of inhibited FGF2 signaling by administration of SU5402, an FGFR inhibitor. It was found that SU5402 itself evoked depressive-like behaviors, induced microglia activation, increased production of pro-inflammatory cytokines including IL-1ß, IL-6 and TNF-α, and decreased the expression of CX3CL1. Two lines of results that FGF2 signaling and FGFR inhibitor can effectively but oppositely modulate the regulation of microglia and the generation of depressive-like behavior, suggesting that microglia-regulated mechanisms may underlie the antidepressant role of FGF2. The present data provide novel insights into the understanding of mechanism of neuroinflammation-associated depression and may serve as a novel mechanism-based target for the treatment of inflammation-related depression.

Blocking p38 Signaling Reduces the Activation of Pro-inflammatory Cytokines and the Phosphorylation of p38 in the Habenula and Reverses Depressive-Like Behaviors Induced by Neuroinflammation.

Increasing evidence has demonstrated that neuroinflammation contributes to the development of depressive-like behaviors, in both animal models and human patients; however, the brain areas and signaling pathways involved are still elusive. Recent studies have suggested novel roles of the habenula in the onset of depression and other psychiatric disorders; however, there is no evidence for whether the habenula has a function in neuroinflammation-induced depression. Using an animal model of depression, which is induced by the repeated central administration of lipopolysaccharide (LPS), we examined whether cytokine expression and p38 signal activation in the habenula were involved in the depressive-like behaviors. Body weight, saccharin preference test, and tail suspension test were used to measure depressive-like behaviors. Immunohistochemistry, quantitative-polymerase chain reaction (q-PCR), and western blot were used to measure the expression of tumor necrosis factor-α (TNF-α), interleukin-10 (IL-10), and the phosphorylation of p38 in the habenula. The results showed that central LPS administration induced depressive-like behaviors, characterized by anhedonia in the saccharin preference test and increased immobility in the tail suspension test. Central LPS administration also significantly increased the p-p38 level in microglial cells and increased TNF-α expression in the habenula. Treatment with fluoxetine, a widely prescribed antidepressant, or SB203580, a p38-specific inhibitor, reversed the depressive-like behaviors, normalized the alterations in p-p38 and TNF-α levels and increased the levels of the anti-inflammatory cytokine IL-10 in the habenula. The present findings suggest that the habenula is involved in the pathophysiology of behavioral depression induced by neuroinflammation, and the p38 pathway may serve as a novel mechanism-based target for the treatment of inflammation-related depression.

The Predictive and Prognostic Role of Stromal Tumor-infiltrating Lymphocytes in HER2-positive Breast Cancer with Trastuzumab-based Treatment: a Meta-analysis and Systematic Review.

Background Tumor-infiltrating lymphocytes (TILs) are white blood cells that have left the bloodstream and migrated into a tumor, involving in the prognosis of breast cancer (BC) patients. Published studies reported the value of TILs in patients with HER2-positive receiving trastuzumab-based treatment. However, the results obtained remain controversial. Here, we conducted this study to explore the predictive and prognostic role of TILs for HER2-positive BC patients receiving trastuzumab therapies. Method To identify the related published studies, a comprehensive literature search dating up to July 2017 was performed in the databases of PubMed, PMC, Web of Science and China National Knowledge Infrastructure (CNKI) according to predefined selection criteria. The pathologic complete response (pCR) and survival outcome of patients were measured by odds ratio (OR) and hazard ratio (HR) with corresponding 95% confidence interval (95% CI), respectively. The association between TILs and trastuzumab benefit was analyzed by using STATA version 11.0. Result Eleven eligible studies comprising 3228 patients were identified in the present study. The pooled results showed that high level of TILs was associated with a significantly improved pCR rate (OR = 1.32; 95% CI = 1.10-1.60) and longer survival (HR = 0.97; 95% CI = 0.96-0.99), particularly in the subgroups of retrospective study design and 10% INC cut-off value. Moreover, stratified analysis revealed that elevated TILs was a predictor of higher pCR rate in the Asian population and improved survival in the subgroups of Caucasian population and multivariate analysis. Conclusion This meta-analysis indicated that the level of stromal TILs was an independent predictive and prognostic marker for better outcome in HER2-positive BC patients receiving trastuzumab-based treatment. High level of TILs was significantly associated with trastuzumab benefit.

Association between SNPs in Long Non-coding RNAs and the Risk of Female Breast Cancer in a Chinese Population.

Long non-coding RNAs (LncRNAs) have been reported to be involved in tumorigenesis and tumor progression. Single nucleotide polymorphisms (SNPs) in the lncRNAs also play a vital role in carcinogenesis. The aim of this study was to assess the relationships between the four selected tagSNPs (rs944289, rs3787016, rs1456315, rs7463708) in the lncRNAs and the risk of female breast cancer in a Chinese population. A case-control study was carried out involving in a total of 439 breast cancer patients and 439 age-matched healthy controls. The genotyping was performed with Sequenom MassARRAY and the expression of estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor-2 (HER-2) in tumor tissues was measured by the immunohistochemistry (IHC) assay. We found that rs3787016 TT genotype (adjusted odds ratio (OR) = 1.62, 95% confidence interval (CI) = 1.09-2.41, P = 0.018) was associated with an increased risk of female breast cancer, especially among the patients with premenopausal status (adjusted OR = 2.55, 95% CI = 1.30-4.97, P = 0.006). Moreover, a statistically significant increased risk of the rs3787016 TT genotype was observed among the patients with advanced tumor stage (Ⅲ and Ⅳ), poor histological grade (G3-G4), positive lymph node involvement, positive expression of ER and PR and negative expression of HER-2; rs7463708 GT and GT/GG genotype were associated with decreased risk of breast cancer in the subgroup of patients with postmenopausal status (GT versus (vs.) TT: adjusted OR = 0.67, 95% CI = 0.46-0.99, P = 0.043; GT/GG vs. TT: adjusted OR = 0.68, 95% CI = 0.47-0.98, P = 0.041) and tumor late-stage (GT vs. TT: adjusted OR = 0.65, 95% CI = 0.43-0.97, P = 0.037; GT/GG vs. TT: adjusted OR = 0.65, 95% CI = 0.44-0.96, P = 0.029). In short, rs3787016 TT genotype was associated with increased breast cancer risk and clinicopathologic features of the tumor, especially among premenopausal women.

Association of Genetic Polymorphisms in the LncRNAs with Gastric Cancer Risk in a Chinese Population.

Background: Genome-wide association studies have identified that polymorphisms in 8q24 confer susceptibility to gastric cancer. Polymorphisms in the lncRNA PRNCR1, PCAT1, and CCAT2 transcribed from the 8q24 locus have a potential risk for gastric cancer. Methods: To evaluate whether there is such an association in Chinese population, a case-control study enrolled 494 patients and 494 healthy controls was carried out. Sequenom MassARRAY platform was used for genotyping. Results: This study showed that rs16901946 G allele was associated with increased risk of gastric cancer (AG: adjusted OR = 1.33, 95% CI =1.02-1.73, p=0.033; GG: adjusted OR = 2.07; 95% CI = 1.11-3.86, p=0.023, AG/GG: adjusted OR = 1.39, 95% CI = 1.08-1.1.79, p=0.011; additive model: adjusted OR = 1.37; 95% CI = 1.10-1.70, p=0.004). Stratified analysis revealed that the increased risk was more evident in the cohort of younger subjects (adjusted OR = 1.84, 95% CI = 1.18-2.87, p=0.007), males (adjusted OR = 1.55, 95% CI = 1.15-2.08, p=0.004), positive Helicobacter pylori infection (adjusted OR = 1.44, 95% CI = 1.02-2.03, p=0.041), gastric cardia adenocarcinoma (adjusted OR = 1.61, 95% CI = 1.10-2.35, p=0.014), and tumor stage T1-T2 (adjusted OR = 1.58, 95% CI = 1.10-2.28, p=0.013). Conclusions: Our study suggested that rs16901946 G allele carriers have an increased risk of gastric cancer, and the risk could be enhanced by the interactions between the polymorphism and age, sex, Helicobacter pylori infection.

Combination of preoperative NLR, PLR and CEA could increase the diagnostic efficacy for I-III stage CRC.

BACKGROUND: Inflammation plays an important role in the development and progression of CRC. The members of inflammatory biomarkers, preoperative NLR and PLR, have been proved by numerous studies to be promising prognostic biomarkers for CRC. However, the diagnostic value of the two biomarkers in CRC remains unknown, and no study reported the combined diagnostic efficacy of NLR, PLR and CEA. METHODS: Five hundred and fifty-nine patients with I-III stage CRC undergoing surgical resection and 559 gender- and age-matched healthy controls were enrolled in this retrospective study. NLR and PLR were calculated from preoperative peripheral blood cell count detected using white blood cell five classification by Sysmex XT-1800i Automated Hematology System and serum CEA were measured by electrochemiluminescence by ELECSYS 2010. The diagnostic performance of NLR, PLR and CEA for CRC was evaluated by ROC curve. RESULTS: Levels of NLR and PLR in the cases were significantly higher than them in the healthy controls. ROC curves comparison analyses showed that the diagnostic efficacy of NLR (AUC=.755, 95%CI=.728-.780) alone for CRC was significantly higher than PLR (AUC=.723, 95%CI=.696-.749, P=.037) and CEA (AUC=.690, 95%CI=.662-.717, P=.002) alone. In addition, the diagnostic efficacy of the combination of NLR, PLR and CEA(AUC=.831, 95%CI=.807-.852)for CRC was not only significantly higher than NLR alone but also higher than any combinations of the two of these three biomarkers (P<.05). Moreover, the NLR and PLR in the patients with TNM stage I/II was higher than that in the healthy controls, and patients with stage III had a higher NLR and PLR than those with stage I/II, but no significant difference was observed. CONCLUSION: Our study indicated that preoperative NLR could be a CRC diagnostic biomarker, even for early stage CRC, and the combination of NLR, PLR and CEA could significantly improve the diagnostic efficacy.

Nucleotide excision repair pathway gene polymorphisms are linked to breast cancer risk in a Chinese population.

Polymorphisms in nucleotide excision repair (NER) pathway genes are associated with the risk of breast cancer, but the relevance of these associations appeared to vary according to the ethnicity of the subjects. To systemically evaluate the potential associations between NER polymorphisms and breast cancer risk in a Chinese population, we carried out a case-control study on 450 breast cancer patients and 430 healthy controls. Sequenom MassARRAY was used for genotyping, and immunohistochemistry was performed to detect estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER-2) expression in tumor tissue. Our results showed that ERCC1 rs11615 (additive model: ORadjusted: 1.36, 95% CI: 1.08-1.71, p = 0.009), XPC rs2228000 (additive model: ORadjusted: 1.39, 95% CI: 1.13-1.72, p = 0.002) and ERCC2/XPD rs50872 (additive model: ORadjusted: 1.32, 95% CI: 1.04-1.67, p = 0.021) were associated with an increased risk of breast cancer. Stratified analysis revealed three polymorphisms (rs11615, rs1800975, and rs50872) to be associated with breast cancer in menopausal females. Three polymorphisms were associated with specific breast cancer grades (rs11615 with grade 3, rs2228000 and rs50872 with grade 1-2). Two polymorphisms (rs2228001 and rs50872) were associated with the risk of breast cancer with negative lymph node involvement. rs1800975 and rs50872 were associated with the risk of ER- and PR- breast cancer, whereas rs11615 was associated with the risk of ER+ and PR+ breast cancer. We found that carriers of the T allele of ERCC1 rs11615, XPC rs2228000 and rs50872, particularly in postmenopausal females, have an increased risk of breast cancer.

MiR-608, pre-miR-124-1 and pre-miR26a-1 polymorphisms modify susceptibility and recurrence-free survival in surgically resected CRC individuals.

Genetic variation within microRNA (miRNA) may result in its abnormal folding or aberrant expression, contributing to colorectal turmorigenesis and metastasis. However, the association of six polymorphisms (miR-608 rs4919510, miR-499a rs3746444, miR-146a rs2910164, pre-miR-143 rs41291957, pre-miR-124-1 rs531564 and pre-miR-26a-1 rs7372209) with colorectal cancer (CRC) risk, therapeutic response and survival remains unclear. A retrospective study was carried out to investigate the association in 1358 0-III stage resected CRC patients and 1079 healthy controls using Sequenom's MassARRAY platform. The results showed that rs4919510 was significantly associated with a decreased susceptibility to CRC in co-dominant, allele and recessive genetic models, and the protective role of rs4919510 allele G and genotype GG was more pronounced among stage 0-II cases; significant association between rs531564 and poor RFS was observed in cases undergoing adjuvant chemo-radiotherapy in co-dominant, allele and dominant models; moreover, there was a positive association between rs7372209 and recurrence-free survival in stage II cases in co-dominant and over-dominant models; additionally, a cumulative effect of rs531564 and rs7372209 at-risk genotypes with hazard ratio at 1.30 and 1.95 for one and two at-risk genotypes was examined in stage II cases, respectively. Our findings indicated that rs4919510 allele G and genotype GG were protective factors for 0-II stage CRC, rs7372209 and rs531564 could decrease RFS in II stage individuals and resected CRC patients receiving adjuvant chemo-radiology.

MicroRNA expression profiles predict progression and clinical outcome in lung adenocarcinoma.

Lung cancer is one of the leading causes of cancer death worldwide. Accumulating evidence has indicated that microRNAs (miRNAs) can be proposed as promising diagnostic and prognostic markers for various cancers. The current study analyzed the miRNA expression profiles of 418 lung adenocarcinoma (LUAD) cases obtained from The Cancer Genome Atlas dataset, with the aim to investigate the relationship of miRNAs with progression and prognosis of LUAD. A total of 185 miRNAs were found to be differentially expressed between LUAD tumor tissues and adjacent normal tissues. Among them, 13, 10, 0, and 10 miRNAs were discovered to be associated with pathologic T, N, M, and Stage, respectively. Interestingly, mir-200 family (mir-200a, mir-200b, and mir-429) was shown to play a critical role in the progression of LUAD. In the multivariate Cox regression analysis, mir-1468 (P=0.009), mir-212 (P=0.026), mir-3653 (P=0.012), and mir-31 (P=0.002) were significantly correlated with recurrence-free survival. With regard to overall survival, mir-551b (P=0.011), mir-3653 (P=0.016), and mir-31 (P=0.001) were proven as independent prognostic markers. In summary, this study identified the cancer-specific miRNAs that may predict the progression and prognosis of LUAD.

Enhanced Platelet Response to Clopidogrel in Abcc3-deficient Mice Due to Its Increased Bioactivation.

Resistance of the patient to clopidogrel (an inactive prodrug) has been recently reported to be associated with increased messenger RNA expression of ABCC3 that encodes MRP3 (multidrug resistance-associated protein 3). However, there is no evidence showing the effects of MRP3 on altered platelet responses to clopidogrel and their underlying mechanisms. To further clarify whether the presence or absence of Mrp3 could affect the formation of and response to clopidogrel active metabolite (CAM) in Abcc3 knockout (KO) versus wild-type (WT) mice, we determined pharmacokinetic profiles of clopidogrel and CAM and measured inhibition of adenosine diphosphate-induced platelet aggregation by clopidogrel after administration of a single oral dose of clopidogrel to KO and WT mice, respectively. Results indicated that Abcc3 KO mice exhibited increased formation of CAM and greater systemic exposure to clopidogrel and enhanced inhibition of adenosine diphosphate-induced platelet aggregation ex vivo by clopidogrel when compared with well-matched WT mice. We conclude that Abcc3 KO mice have enhanced platelet response to clopidogrel due to increased formation of CAM.

Platelet-to-lymphocyte ratio could be a promising prognostic biomarker for survival of colorectal cancer: a systematic review and meta-analysis.

Inflammation is one of the most important causes leading to colorectal carcinogenesis, and inflammatory biomarkers such as the platelet-to-lymphocyte ratio (PLR) might predict survival in colorectal cancer (CRC). However, the prognostic value of PLR in CRC patients remains controversial. The prognostic value of PLR was comprehensively analyzed in 12 articles including 3541 CRC patients (10 for overall survival (OS), seven for disease-free survival (DFS), three for recurrence-free survival (RFS), and three for cancer-specific survival (CSS)) in this study. The overall pooled hazard ratios (HRs) of PLR for OS, DFS, and CSS were significant at 1.29 (95% confidence interval, CI = 1.13-1.47, P H = 0.149), 1.43 (95% CI = 1.03-1.97, P H = 0.025), and 1.26 (95% CI = 1.04-1.52, P H = 0.223), respectively. However, there was no evidence of significance for RFS (HR = 1.29, 95% CI = 0.98-1.70, P H = 0.231) in our study. Stratified analyses indicated elevated PLR was a predictor of poor OS (metastatic patients) and DFS (Caucasian population) and was also significantly associated with OS in univariate analysis (HR = 1.35, 95% CI = 1.14-1.60, P H = 0.532) and those only treated surgically (HR = 1.37, 95% CI = 1.10-1.70, P H = 1.080). However, our findings indicated that elevated PLR is a promising prognostic biomarker for colorectal cancer, especially in metastatic Caucasian CRC patients.

Prognostic performance of lymphocyte-to-monocyte ratio in diffuse large B-cell lymphoma: an updated meta-analysis of eleven reports.

PURPOSE: The findings on the prognostic value of lymphocyte-to-monocyte ratio (LMR) in diffuse large B-cell lymphoma (DLBCL) are inconsistent. This meta-analysis was conducted to more precisely evaluate the prognostic significance of LMR in DLBCL. METHODS: This analysis combined eleven studies with 4,578 patients aiming to assess the association of LMR with overall survival (OS) and progression-free survival (PFS) in DLBCL. Data from studies directly reporting a hazard ratio (HR) with 95% corresponding confidence interval (CI) in multivariate analysis were pooled to estimate the effect. RESULTS: Our results suggested that patients with decreased LMR had shorter OS (HR =1.79, 95% CI =1.54-2.08, P<0.001) and PFS (HR =2.21, 95% CI =1.80-2.72, P<0.001) in DLBCL. Stratified analyses indicated that each confounder showed consistent prognostic value in DLBCL. There was no significant heterogeneity for PFS (P H=0.192) and OS (P H=0.212) among the enrolled studies. CONCLUSION: This meta-analysis indicated that decreased LMR might be a marker in the prediction of poor prognosis for patients with DLBCL.

Association of the DISC1 and NRG1 genetic polymorphisms with schizophrenia in a Chinese population.

Polymorphisms in Disrupted-in-Schizophrenia 1 (DISC1) and Neuregulin 1 (NRG1) might be associated with schizophrenia; however, the conclusions of relevant studies were inconsistent across different ethnic populations. This population-based case-control study was carried out to determine whether polymorphisms in these two genes could be associated with schizophrenia in the Chinese population. A case-control study of 248 schizophrenia patients and 236 controls was performed with the Sequenom MassARRAY platform. The results revealed that the DISC1 rs821616 heterozygous (AT vs. AA: adjusted OR, 1.98, 95%CI: 1.30-3.02) and co-dominant (AT/TT vs. AA: adjusted OR=1.94; 95%CI: 1.29-2.92) patterns were associated with increased risk for developing schizophrenia in all participants and subgroups (stratified by sex and age at onset), respectively. Moreover, in the male subgroup, the DISC1 rs821597 genotype GA or GA/AA exhibited increased risk of schizophrenia. For NRG1 polymorphisms, in the early onset subgroup (≤25years), the rs3924999 G/G genotype was susceptible to schizophrenia. The interaction of DISC1 rs821616 T allele with the NRG1 rs3924999 A allele or that of DISC1 rs821597 A allele with NRG1 rs3924999 A allele had synergic effects on the development of schizophrenia. This study concluded that carriers of the DISC1 rs821616 T allele have increased risk for developing schizophrenia, and that the DISC1 rs821597 A allele was susceptible to schizophrenia for the male, and that there are marked interactions between the DISC1 rs821616 T and/or rs821597 A alleles and the NRG1 rs3924999 A allele for the development of schizophrenia.