Survival benefits of human papillomavirus 16 infection in patients with esophageal squamous cell carcinoma undergoing chemoradiotherapy: A retrospective cohort study.

The role of human papillomavirus 16 (HPV 16) in esophageal squamous cell carcinoma (ESCC) remains uncertain. Therefore, this study aimed to investigate the prevalence of HPV 16 in patients with ESCC and its impact on theirprognosis. HPV 16 was detected using FISH, and TP53 status was evaluated via immunohistochemistry. The factors influencing prognosis were ananalyzed using the Log-rank test and Cox regression analyses. Among 178 patients with ESCC, 105 and 73 patients were categorized into concurrent chemoradiotherapy (CCRT) and postoperative chemoradiotherapy (POCRT) cohorts, respectively. Among 178 patients, 87 (48.87%) tested positive for HPV 16. Log-rank tests revealed that the overall survival (OS) of patients with ESCC who were HPV 16-positive was longer than that of those who were HPV 16-negative (median OS: 57 months vs. 27 months, p < 0.01**). HPV 16 infection and TP53 mutation status were identified as independent events. The OS of patients with mutant TP53 who were HPV 16-positive was longer than that of those who were HPV 16-negative in both CCRT and POCRT cohorts (p = 0.002** for CCRT cohorts and p = 0.0023** for POCRT cohorts). Conversely, HPV 16 infection had no effect on OS in the wild-type TP53 subgroup (p = 0.13 and 0.052 for CCRT and POCRT cohorts, respectively). As a conclusion, the positive rate of HPV 16 in ESCC in this study was 48.87% (87/178). Among the patients with ESCC who had TP53 mutation, those who were HPV 16-positive exhibited a better prognosis than those who were HPV 16-negative.

Mechanochemical Synthesis of Thiadiazole Functionalized COF as Oil-Based Lubricant Additive for Reducing Friction and Wear.

In this work, the functionalized covalent organic framework (COF) was prepared via a convenient ball milling process. The aldehyde group terminated COF-F reacted with amino thiadiazole in the ball milling jar under mechanical forces; hence, the thiadiazole functionalized COF-F was obtained and denoted as Thdz@COF-F. The as-prepared Thdz@COF-F serves as an oil-based lubricant additive and exhibits remarkable tribological properties, which can reduce the average friction coefficient of base oil from 0.169 to 0.102 and decrease the wear volume by 87.0%. The antifriction and antiwear performances are mainly due to the repairing effect of Thdz@COF-F nanoparticles and the protective tribo-film that averts the direct contact of friction pairs. In addition, through the ball milling method, triazole and thiazole functionalized COF-F were also prepared and represented good lubrication performance, demonstrating the feasibility of this mechanochemical synthesis method for functionalized COFs.

Induced expression of AMOT reverses adriamycin resistance in breast cancer cells.

Adriamycin (ADR) is widely used against breast cancer, but subsequent resistance always occurs. YAP, a downstream protein of angiomotin (AMOT), importantly contributes to ADR resistance, whereas the mechanism is largely unknown. MCF-7 cells and MDA-MB-231 cells were used to establish ADR-resistant cell. Then, mRNA and protein expressions of AMOT and YAP expressions were determined. After AMOT transfection alone or in combination with YAP, the sensitivity of the cells to ADR were evaluated in vitro by examining cell proliferation, apoptosis, and cell cycle, as well as in vivo by examining tumor growth. Additionally, the expressions of proteins in YAP pathway were determined in AMOT-overexpressing cells. In the ADR-resistant cells, the expression of AMOT was decreased while YAP was increased, respectively, and the nucleus localization of YAP was increased at the same time. After AMOT overexpression, these were inhibited, whereas the cell sensitivity to ADR was enhanced. However, the AMOT-induced changes were significantly suppressed by YAP knockdown. The consistent results in vivo showed that AMOT enhanced the inhibition of ADR on tumor growth, and inhibited YAP signaling, evidenced by decreased levels of YAP, CycD1, and p-ERK. Our data revealed that decreased AMOT contributed to ADR resistance in breast cancer cells, which was importantly negatively mediated YAP. These observations provide a potential therapy against breast cancer with ADR resistance.

Genetically predicted high sex hormone binding globulin was associated with decreased risk of polycystic ovary syndrome.

BACKGROUND: Previous observational studies have indicated an inverse correlation between circulating sex hormone binding globulin (SHBG) levels and the incidence of polycystic ovary syndrome (PCOS). Nevertheless, conventional observational studies may be susceptible to bias. Consequently, we conducted a two-sample Mendelian randomization (MR) investigation to delve deeper into the connection between SHBG levels and the risk of PCOS. METHODS: We employed single-nucleotide polymorphisms (SNPs) linked to serum SHBG levels as instrumental variables (IVs). Genetic associations with PCOS were derived from a meta-analysis of GWAS data. Our primary analytical approach relied on the inverse-variance weighted (IVW) method, complemented by alternative MR techniques, including simple-median, weighted-median, MR-Egger regression, and MR Pleiotropy RESidual Sum and Outlier (MR-PRESSO) testing. Additionally, sensitivity analyses were conducted to assess the robustness of the association. RESULTS: We utilized 289 SNPs associated with serum SHBG levels, achieving genome-wide significance, as instrumental variables (IVs). Our MR analyses revealed that genetically predicted elevated circulating SHBG concentrations were linked to a reduced risk of PCOS (odds ratio (OR) = 0.56, 95% confidence interval (CI): 0.39-0.78, P = 8.30 × 10-4) using the IVW method. MR-Egger regression did not detect any directional pleiotropic effects (P intercept = 0.626). Sensitivity analyses, employing alternative MR methods and IV sets, consistently reaffirmed our results, underscoring the robustness of our findings. CONCLUSIONS: Through a genetic epidemiological approach, we have substantiated prior observational literature, indicating a potential causal inverse relationship between serum SHBG concentrations and PCOS risk. Nevertheless, further research is needed to elucidate the underlying mechanism of SHBG in the development of PCOS.

Fabrication of Zwitterionic Polymer-Functionalized Onion-like Carbon Nanoparticles as Aqueous Lubricant Additives.

Onion-like carbon (OLC) is a kind of carbon material with a graphene-like structure and large interlayer spacing, favorable to a good lubricating performance. Herein, a facile method is presented for the preparation of functionalized OLC nanoparticles from candle soot with surface modification. The OLC nanoparticles are collected from combustion soot with candle burning via a simple heat treatment, and then the zwitterionic polymer (polyethylenimine-quaternized derivative, PEIS) can self-assemble onto the OLC surface with epigallocatechin gallate via Michael addition and Schiff-base reaction, thus obtaining PEIS-functionalized OLC nanoparticles (PEIS@OLC). The grafting zwitterionic polymer PEIS endows the OLC nanoparticles with good hydrophilic performance, so the as-obtained PEIS@OLC exhibits outstanding dispersion and lubricating property as a water-based lubricant additive. Compared to pure water, the average coefficient of friction decreases to 0.110 from 0.512, and the corresponding wear volume is reduced by 61.02% with 1.5 wt % addition. The improved lubricating property is mainly due to the synergetic effect of the protective film induced by the tribochemical reaction and the hydration film of zwitterionic polymer PEIS. Besides, the OLC nanoparticles could also display the nanoscale rolling and repairing effects at the friction contact interface, resulting in reduction of friction and wear.

In Situ Surface-Initiated ATRP Mediated by Gallium-Based Liquid Metal Nanodroplets.

Surface-initiated atom transfer radical polymerization (SI-ATRP) is one of the most popular methods for surface modifications with functional polymer films, which has attracted significant attention in recent years. Herein, a facile method of gallium-based liquid metal (GLM) nanodroplets mediated SI-ATRP to prepare polymer brushes on GLM surfaces is reported. The ATRP initiator modified GLM (GLM-Br) nanodroplets act as a substrate for the in situ SI-ATRP and participate as a reducing agent to reduce Cu(II) deactivators to Cu(I) activators. UV-vis spectra confirm the feasibility of the in situ SI-ATRP and indicate that the thickness and density of polymer brushes play an important role in performing a successful ATRP on GLM nanodroplets surfaces. Homo- and block copolymers, poly(3-sulfopropyl methacrylate potassium salt) (PSPMA) and poly((2-dimethylamino)ethyl methacrylate-b-(3-sulfopropyl methacrylate potassium salt)) P(DMAEMA-b-SPMA) are successfully grafted to the GLM nanodroplets. Polymer brushes modified GLM nanodroplets show potential applications such as friction reduction and oil-water emulsion separation. GLM nanodroplets mediated SI-ATRP provides a novel and robust approach to preparing multifunctional GLM nanodroplets for different applications.

Descriptive analysis of depression among adolescents in Huangshi, China.

BACKGROUND: More adolescents suffered from depressive disorder, and what was worse, the morbidity increased annually. The situation was getting worse during COVID-19 pandemic. The prevalence of depression among adolescents in China has increased a lot due to social and economic development, family-associated reasons, academic stress, interpersonal relationships, and so on. OBJECTIVE: This study aimed to determine the prevalence, gender differences, risk factors, and abnormal illness behaviors of depression among adolescents in Huangshi, China. METHODS: A descriptive analysis was conducted based on the data from clinical interviews and self-reports by the patients. Depression was assessed and diagnosed using the DSM-5 Diagnostic and Statistical Manual of Mental Disorders. RESULTS: Depression was most frequently seen in 674 patients with mental illnesses (282, 41.84%). The male-to-female ratio was 1:2.44, and their age ranged from 9 to 18. The majority of patients are in high school (261/282, 92.55%), and the highest morbidity occurred at 16 years. More cases were diagnosed in urban than in rural areas. Genetic factors, school violence, academic stress, sleep disorders, and family-related factors were essential factors leading to depression among adolescents. Most patients had sleep disorders (84.75%). In family-related factors, left-behind children and unrecognized/misunderstood by their families were prominently diagnosed with depression. A large portion of individuals with depression felt apathetic, solitary, and sluggish and were unable to study, work, and live normally (212/282, 75.18%); they even committed suicide or attempted suicide (228/282, 80.85%) and inflicted self-harm (146/282, 51.77%). CONCLUSIONS: An increasing trend of depression has been observed since 2018, especially in 2021. This depression has led to suicide or suicidal attempts and self-harm, reflecting the severity of mental health among adolescents in Huangshi. Therefore, this study aimed to draw the attention of society, families, and schools to the importance of mental health among adolescents, providing guidance and references for the prevention, diagnosis, and treatment of young depressive disorders in China.

DSA-Net: Infrared and Visible Image Fusion via Dual-Stream Asymmetric Network.

Infrared and visible image fusion technologies are used to characterize the same scene using diverse modalities. However, most existing deep learning-based fusion methods are designed as symmetric networks, which ignore the differences between modal images and lead to source image information loss during feature extraction. In this paper, we propose a new fusion framework for the different characteristics of infrared and visible images. Specifically, we design a dual-stream asymmetric network with two different feature extraction networks to extract infrared and visible feature maps, respectively. The transformer architecture is introduced in the infrared feature extraction branch, which can force the network to focus on the local features of infrared images while still obtaining their contextual information. The visible feature extraction branch uses residual dense blocks to fully extract the rich background and texture detail information of visible images. In this way, it can provide better infrared targets and visible details for the fused image. Experimental results on multiple datasets indicate that DSA-Net outperforms state-of-the-art methods in both qualitative and quantitative evaluations. In addition, we also apply the fusion results to the target detection task, which indirectly demonstrates the fusion performances of our method.

Effects of zero-valent iron and magnetite on ethanol and lactic acid production in the anaerobic fermentation of food waste.

With the increasing global concern about food waste management, finding efficient ways to convert it into valuable products is crucial. The addition of zero-valent iron and magnetite to enhance ethanol and lactic acid fermentation yields from food waste emerges as a potential solution. This study compared the effects of 50-nm and 500-nm particle sizes of zero-valent iron and magnetite on ethanol and lactic acid fermentation and analyzed the mechanism of action from the perspective of organic matter material transformation and microbiology. The experimental results showed that 500-nm particle size magnetite and zero-valent iron could promote the hydrolysis of polysaccharides and proteins. 500-nm particle size magnetite could increase ethanol production (1.4-fold of the control), while 500-nm particle size zero-valent iron could increase lactic acid production (2.8-fold of the control). Metagenomic analysis showed that 500-nm magnetite increased the abundance of genes for amino acid metabolic functions, while 500-nm zero-valent iron increased the abundance of glycoside hydrolase genes (1.3-fold of the control). It's worth noting that while these findings are promising, they are based on controlled experimental conditions, and real-world applications may vary. his research not only offers a novel approach to augmenting anaerobic fermentation yields but also contributes to sustainable food waste management practices, potentially reducing environmental impacts and creating valuable products.

Effects of iron additives on the removal of antibiotics and antibiotic resistance genes in anaerobic fermentation of food waste.

The presence of antibiotics and antibiotic resistance genes (ARGs) in food waste (FW) during anaerobic fermentation poses significant environmental and health risks. This study elucidated the potential of iron additives, specifically 500-nm and 50-nm zero-valent iron (ZVI) and magnetite, in mitigating these contaminants. These findings revealed that 500-nm magnetite significantly reduced tetracyclines by 81.04%, while 500-nm ZVI effectively reduced cefotaxime by 89.90%. Furthermore, both 500-nm and 50-nm ZVI were observed to decrease different types and abundance of heavy metal resistance and virulence genes. Interestingly, while 500-nm ZVI reduced the overall abundance of ARGs by 50%, 500-nm magnetite primarily reduced the diversity of ARGs without significantly impacting their abundance. These results elucidate the efficacy of iron additives in addressing antibiotic contamination and resistance during the anaerobic fermentation process of FW. The findings acquired from this study mitigate the development of innovative and environmentally sustainable technologies for FW treatment, emphasizing the reduction of environmental risks and enhancement of treatment efficiency.

A novel self-assemble peptide drug design of AKT1 for anaplastic thyroid cancer therapy.

Anaplastic thyroid cancer (ATC) is an undifferentiated subtype of thyroid cancer with a markedly poor survival prognosis, estimated to occur 3-5 months after diagnosis. Akt activation is reportedly involved in tumorigenesis during ATC and represents a new therapeutic target. Based on the Akt1/bisubstrate complex structure and artificial intelligence-assisted peptide drug screening, we designed a self-assemble Akt1-targeting peptide drug exhibiting a 0.89-nm structure and potential killing ability in ATC cells. The developed self-assemble Akt1-targeting peptide drug presented IC50 values of 18.2 µM and 12.4 µM in 8303C and 8505C cells, respectively, after 72 h of incubation.

Promoter methylation of transient receptor potential melastatin-related 7 (TRPM7) predicts a better prognosis in patients with Luminal A breast cancers.

Breast cancer is the most common female tumors arising worldwide, and genetic and epigenetic events are constantly accumulated in breast tumorigenesis. The melastatin-related transient receptor potential 7 channel (TRPM7) is a nonselective cation channel, mainly maintaining Zn2+, Ca2+ and Mg2+ homeostasis. It is also involved in regulating proliferation and migration in various cancers including breast cancer. However, epigenetic alterations (such as promoter methylation) of TRPM7 and their correlation with clinical outcomes in breast cancer patients remain largely unclear. In this study, we found that TRPM7 was highly expressed in the luminal A subtype of breast cancers but no other subtypes compared with GTEx (Genotype-Tissue Expression Rad) or normal samples by analyzing the TCGA database. Correspondingly, TRPM7 was methylated in 42.7% (93 of 219) of breast cancers. Further studies found that promoter methylation of TRPM7 were significantly associated with better clinical outcomes in breast cancer patients, especially in the Luminal A subtype. Besides, methylated TRPM7 was correlated with less number of metastatic lymph nodes and longer local failure free survival time in this subtype. In summary, our data indicate that promoter methylation of TRPM7 may predict poor prognosis in patients with luminal A breast cancer.

Improved U-Net3+ with stage residual for brain tumor segmentation.

BACKGROUND: For the encoding part of U-Net3+,the ability of brain tumor feature extraction is insufficient, as a result, the features can not be fused well during up-sampling, and the accuracy of segmentation will reduce. METHODS: In this study, we put forward an improved U-Net3+ segmentation network based on stage residual. In the encoder part, the encoder based on the stage residual structure is used to solve the vanishing gradient problem caused by the increasing in network depth, and enhances the feature extraction ability of the encoder which is instrumental in full feature fusion when up-sampling in the network. What's more, we replaced batch normalization (BN) layer with filter response normalization (FRN) layer to eliminate batch size impact on the network. Based on the improved U-Net3+ two-dimensional (2D) model with stage residual, IResUnet3+ three-dimensional (3D) model is constructed. We propose appropriate methods to deal with 3D data, which achieve accurate segmentation of the 3D network. RESULTS: The experimental results showed that: the sensitivity of WT, TC, and ET increased by 1.34%, 4.6%, and 8.44%, respectively. And the Dice coefficients of ET and WT were further increased by 3.43% and 1.03%, respectively. To facilitate further research, source code can be found at: https://github.com/YuOnlyLookOne/IResUnet3Plus . CONCLUSION: The improved network has a significant improvement in the segmentation task of the brain tumor BraTS2018 dataset, compared with the classical networks u-net, v-net, resunet and u-net3+, the proposed network has smaller parameters and significantly improved accuracy.

The Amino Acid Permease MoGap1 Regulates TOR Activity and Autophagy in Magnaporthe oryzae.

Rice is an important food crop all over the world. It can be infected by the rice blast fungus Magnaporthe oryzae, which results in a significant reduction in rice yield. The infection mechanism of M. oryzae has been an academic focus for a long time. It has been found that G protein, AMPK, cAMP-PKA, and MPS1-MAPK pathways play different roles in the infection process. Recently, the function of TOR signaling in regulating cell growth and autophagy by receiving nutritional signals generated by plant pathogenic fungi has been demonstrated, but its regulatory mechanism in response to the nutritional signals remains unclear. In this study, a yeast amino acid permease homologue MoGap1 was identified and a knockout mutant of MoGap1 was successfully obtained. Through a phenotypic analysis, a stress analysis, autophagy flux detection, and a TOR activity analysis, we found that the deletion of MoGap1 led to a sporulation reduction as well as increased sensitivity to cell wall stress and carbon source stress in M. oryzae. The ΔMogap1 mutant showed high sensitivity to the TOR inhibitor rapamycin. A Western blot analysis further confirmed that the TOR activity significantly decreased, which improved the level of autophagy. The results suggested that MoGap1, as an upstream regulator of TOR signaling, regulated autophagy and responded to adversities such as cell wall stress by regulating the TOR activity.

SOCS6 promotes radiosensitivity and decreases cancer cell stemness in esophageal squamous cell carcinoma by regulating c-Kit ubiquitylation.

BACKGROUND: Radiotherapy is a major treatment for esophageal squamous cell carcinoma (ESCC). However, HPV infection related radioresistance caused poor prognosis of ESCC. The function of SOCS6, which has been shown to be a tumor suppressor in several cancers, has not been fully investigated up till now. In this manuscript, we aim to further investigate the role of SOCS6 in regulating ESCC radioresistance. METHODS: Fifty-seven ESCC patients were enrolled for survival analysis. SOCS6 was stably overexpressed in HPV+ ESCC and ESCC cells, and cells were treated with radiation and then subjected to colony formation assays. Expression of DNA damage repair regulating proteins were examined by Western blotting. Cell growth, cell migration and cisplatin sensitivity were then analyzed. Sphere formation assays and flow cytometry were used to investigate changes in cancer stem cell (CSC) properties. Immunofluorescent staining and confocal microscopy were used to locate SOCS6 and c-Kit. Ubiquitylation level of c-Kit were analyzed after immunoprecipitation. Then, coimmunoprecipitation (CoIP) of SOCS6 and c-Kit were performed. In vivo, xenograft animal models were treated with radiation to examine the radiosensitivity. RESULTS: SOCS6 is correlated with better prognosis in ESCC patients. Radioresistance is impaired by SOCS6 upregulation, which inhibited cell growth, migration and increased sensitivity to cisplatin. SOCS6 significantly decreased the population of CSCs expressing the surface biomarker CD271 or CD24low/CD44high and their ability of sphere formation. SOCS6 and c-Kit were collocated in the cytoplasm. Blotting of ubiquitin and CoIP experiments indicated that the mechanism was related to ubiquitylation and degradation of the receptor c-Kit. Xenograft tumor mouse model showed that SOCS6 inhibited tumor growth and promoted radiosensitivity in vivo. CONCLUSIONS: Our findings suggest that SOCS6 can promote the radiosensitivity of HPV+ ESCC and ESCC cells and reduce their stemness via ubiquitylation and degradation of c-Kit. Thus, SOCS6 is a potential target for overcoming radioresistance of ESCC.

de Gennes Narrowing and Relationship between Structure and Dynamics in Self-Organized Ion-Beam Nanopatterning.

Investigating the relationship between structure and dynamical processes is a central goal in condensed matter physics. Perhaps the most noted relationship between the two is the phenomenon of de Gennes narrowing, in which relaxation times in liquids are proportional to the scattering structure factor. Here, a similar relationship is discovered during the self-organized ion-beam nanopatterning of silicon using coherent x-ray scattering. However, in contrast to the exponential relaxation of fluctuations in classic de Gennes narrowing, the dynamic surface exhibits a wide range of behaviors as a function of the length scale, with a compressed exponential relaxation at lengths corresponding to the dominant structural motif-self-organized nanoscale ripples. These behaviors are reproduced in simulations of a nonlinear model describing the surface evolution. We suggest that the compressed exponential behavior observed here is due to the morphological persistence of the self-organized surface ripple patterns which form and evolve during ion-beam nanopatterning.

Long non-coding RNA SNGH7 Is activated by SP1 and exerts oncogenic properties by interacting with EZH2 in ovarian cancer.

Long non-coding RNAs (lncRNAs) are key regulators or a range of diseases and chronic conditions such as cancers, but how they function in the context of ovarian cancer (OC) is poorly understood. The Coding-Potential Assessment Tool was used to assess the likely protein-coding potential of SNHG7. SNHG7 expression was elevated in ovarian tumour tissues measured by qRT-PCR. The online database JASPAR was used to predict the transcription factors binding to SNHG7. Twenty-four-well Transwell plates were used for invasion assays. RNA immunoprecipitation was performed to determine RNA-protein associations. EdU assay was introduced to detect cell proliferation. Chromatin immunoprecipitation was performed to confirm the directly interaction between DNA and protein. We discovered that in the context of OC there is a significant up-regulation of the lncRNA SNHG7. Knocking down this lncRNA disrupted both OC cell invasion and proliferation, while its overexpression had the opposite effect. SP1 binding sites were present in the SNHG7 promoter, and chromatin immunoprecipitation (ChIP) confirmed direct SP1 binding to this region, activating SNHG7 transcription. We found that at a mechanistic level in OC cells, KLF2 is a probable SNHG7 target, as we found that SHNCCC16 directly interacts with EZH2 and thus represses KLF2 expression. In summary, this research demonstrates that lncRNA SNHG7 is an SP1-activated molecule that contributes to OC progression by providing a scaffold whereby EZH2 can repress KLF2 expression.

Magnetic resonance imaging-based radiomic features for extrapolating infiltration levels of immune cells in lower-grade gliomas.

PURPOSE: To extrapolate the infiltration levels of immune cells in patients with lower-grade gliomas (LGGs) using magnetic resonance imaging (MRI)-based radiomic features. METHODS: A retrospective dataset of 516 patients with LGGs from The Cancer Genome Atlas (TCGA) database was analysed for the infiltration levels of six types of immune cells using Tumor IMmune Estimation Resource (TIMER) based on RNA sequencing data. Radiomic features were extracted from 107 patients whose pre-operative MRI data are available in The Cancer Imaging Archive; 85 and 22 of these patients were assigned to the training and testing cohort, respectively. The least absolute shrinkage and selection operator (LASSO) was applied to select optimal radiomic features to build the radiomic signatures for extrapolating the infiltration levels of immune cells in the training cohort. The developed radiomic signatures were examined in the testing cohort using Pearson's correlation. RESULTS: The infiltration levels of B cells, CD4+ T cells, CD8+ T cells, macrophages, neutrophils and dendritic cells negatively correlated with overall survival in the 516 patient cohort when using univariate Cox's regression. Age, Karnofsky Performance Scale, WHO grade, isocitrate dehydrogenase mutant status and the infiltration of neutrophils correlated with survival using multivariate Cox's regression analysis. The infiltration levels of the 6 cell types could be estimated by radiomic features in the training cohort, and their corresponding radiomic signatures were built. The infiltration levels of B cells, CD8+ T cells, neutrophils and macrophages estimated by radiomics correlated with those estimated by TIMER in the testing cohort. Combining clinical/genomic features with the radiomic signatures only slightly improved the prediction of immune cell infiltrations. CONCLUSION: We developed MRI-based radiomic models for extrapolating the infiltration levels of immune cells in LGGs. Our results may have implications for treatment planning.

Aberrant methylation and microRNA-target regulation are associated with downregulated NEURL1B: a diagnostic and prognostic target in colon cancer.

BACKGROUND: Aberrant methylation and miRNA-target-gene regulation function as important mechanisms for gene inactivation in colon carcinogenesis. Although a serious of molecular events (such as aberrant alterations of genomics and epigenetics) have been identified to be related to prognostic in colon cancer (CC) patients, beneficial biomarkers for early diagnosis and prognostic evaluation remain largely unknown. METHODS: In our study, the role of NEURL1B, including gene expression analysis, methylation characteristic, miRNA-target regulation, diagnostic and prognostic significance, were evaculated using multiple bioinformatic tools based on TCGA database and clinical samples. RESULTS: Our data showed that NEURL1B was aberrantly downregulated in CC, regardless of the mRNA level or protein level. Moreover, ROC curve and multivariate Cox regression analysis demonstrated that NEURL1B was a diagnostic and independent prognostic facter for CC patients. Of interest, methylation of NEURL1B was also high and closely associated with poor survival in CC. In addition, multiple NEURL1B-target miRNAs were found to be overexpressed in CC tissues. Thus, our findings suggested that NEURL1B participated in the pathological processes of CC as a tumor suppressor gene. Double management, including DNA methylation modification and miRNA-target regulation, were considered to be related to the downregulation of NEURL1B. Importantly, there existing be an significant intersection between miRNAs-target pathways and NEURL1B-target pathways, suggesting that miR-17 and miR-27a might promote tumor cell malignant property by targeting NEURL1B degradation via the activation of PI3K/AKT signaling pathway. CONCLUSIONS: Taking together, the first investigation of NEURL1B in CC provide us a strong evidences that it might be served as a potential biomarkers for early diagnosis and prognostic evaluation in CC.

EML4-ALK, a potential therapeutic target that responds to alectinib in ovarian cancer.

Ovarian cancer is prone to recurrence and chemotherapy resistance. Ovarian tumours of some patients have been positive for anaplastic lymphoma kinase fusion gene expression (ALK+). Preclinical studies indicate that anaplastic lymphoma kinase inhibitor can suppress the growth of ovarian cancer cells and transplantation tumours. Here, we present a patient with metastatic ALK+ high-grade serous ovarian cancer that testing positive for EML4-ALK (microtubule-associated protein-like 4 gene, fused to the anaplastic lymphoma kinase gene), experienced dramatic benefit after administration of the anaplastic lymphoma kinase inhibitor alectinib. This is the first clinical evidence that treatment with alectinib may provide a personalized maximum benefit for patients with high-grade serous ovarian cancer who are positive for EML4-ALK.