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BACKGROUND: The study aimed to identify the optimal model for predicting rectal cancer liver metastasis (RCLM). This involved constructing various prediction models to aid clinicians in early diagnosis and precise decision-making. METHODS: A retrospective analysis was conducted on 193 patients diagnosed with rectal adenocarcinoma were randomly divided into training set (n = 136) and validation set (n = 57) at a ratio of 7:3. The predictive performance of three models was internally validated by 10-fold cross-validation in the training set. Delineation of the tumor region of interest (ROI) was performed, followed by the extraction of radiomics features from the ROI. The least absolute shrinkage and selection operator (LASSO) regression algorithm and multivariate Cox analysis were employed to reduce the dimensionality of radiomics features and identify significant features. Logistic regression was employed to construct three prediction models: clinical, radiomics, and combined models (radiomics + clinical). The predictive performance of each model was assessed and compared. RESULTS: KRAS mutation emerged as an independent predictor of liver metastasis, yielding an odds ratio (OR) of 8.296 (95%CI: 3.471-19.830; p < 0.001). 5 radiomics features will be used to construct radiomics model. The combined model was built by integrating radiomics model with clinical model. In both the training set (AUC:0.842, 95%CI: 0.778-0.907) and the validation set (AUC: 0.805; 95%CI: 0.692-0.918), the AUCs for the combined model surpassed those of the radiomics and clinical models. CONCLUSIONS: Our study reveals that KRAS mutation stands as an independent predictor of RCLM. The radiomics features based on MR play a crucial role in the evaluation of RCLM. The combined model exhibits superior performance in the prediction of liver metastasis. CLINICAL TRIAL NUMBER: Not applicable.
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Neoplasias Hepáticas , Imagen por Resonancia Magnética , Mutación , Proteínas Proto-Oncogénicas p21(ras) , Neoplasias del Recto , Humanos , Neoplasias del Recto/diagnóstico por imagen , Neoplasias del Recto/genética , Neoplasias del Recto/patología , Femenino , Masculino , Neoplasias Hepáticas/secundario , Neoplasias Hepáticas/diagnóstico por imagen , Neoplasias Hepáticas/genética , Persona de Mediana Edad , Estudios Retrospectivos , Proteínas Proto-Oncogénicas p21(ras)/genética , Imagen por Resonancia Magnética/métodos , Anciano , Adenocarcinoma/diagnóstico por imagen , Adenocarcinoma/genética , Adenocarcinoma/secundario , Adulto , Valor Predictivo de las Pruebas , RadiómicaRESUMEN
Long non-coding RNA (LncRNA) SOX21-AS1 has been reported that it plays an important role in biological processes of several cancers. However, how it functions in cervical cancer (CC) still remain unclear. This investigation seeks to explore the impact of SOX21-AS1 on CC cell proliferation, invasion and migration and its association to the FZD3 and the Wnt/ß-catenin signaling pathway. SOX21-AS1 expression levels were detected using real-time quantitative PCR in 20 cases of cervical cancer together with its adjacent tissues and several cervical cancer cell lines. Transgenic technology and functional experiments were conducted to confirm the carcinogenic properties of SOX21-AS1, and western blot was utilized to analyze the regulatory network composed of SOX21-AS1, FZD3 and the Wnt/ß-catenin signaling pathway in CC. Through bioinformatics analysis, we found that the expression of SOX21-AS1 in CC was the highest among 16 kinds of tumor tissues. Moreover, clinical specimens confirmed that both CC tissues and cell lines possessed elevated SOX21-AS1 expressions (P < 0.01). CC cells which stably expressed upregulated SOX21-AS1 were noted to possesses higher rates of metastasis, invasion and proliferation, lower apoptotic rates and higher expression of FZD3,ß-catenin and c-myc (P < 0.01). Conversely, the use of small interfering RNA to inhibit the expression of SOX21-AS1 yielded the opposite results (P < 0.01). SOX21-AS1 functions as an oncogenic LncRNA which enhances CC cell metastasis, invasion and proliferation through FZD3 upregulation via Wnt/ß-catenin-signaling pathway activation. This LncRNA may represent an important biomarker for CC patients.
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Normal human cervical epitheliums infected with HPVs gene in vitro are underlying molecular models to investigate physiological mechanisms of cervical epithelia and cervical disease. The current study aimed to establish a modified culture method for cervical epithelium and explore the feasibility of transfection with HPV-16 E6 gene mediated by lentivirus in primary cervical cells. The cells were dissociated enzymatically using Dispase II combined with 0.25% Trypsin-0.01% ethylenediamine tetracetic acid (EDTA) or Collagenase I. The detached effectiveness of Dispase II at different times was compared. Isolated cells were cultured and subcultured in modified keratinocyte serum-free medium (K-SFM) supplemented with 5% fetal bovine serum (FBS) or K-SFM alone. Cytokeratin was used as the identification of cervical epitheliums. Proliferative capacity and growth curve of cervical epitheliums were evaluated by cell counting kit-8 (CCK-8). The cells at passages 3 were used to infect with HPV-16 E6 gene by lentivirus. The expression of green fluorescent protein (GFP) presented in the infected cells was observed via fluorescence microscopy and the levels of E6 mRNA were detected by quantitative real-time PCR (qRT-PCR). The results indicate that cervical epithelial cells can be isolated successfully by Dispase II combined with 0.25% Trypsin-0.01% EDTA method for 20 hr and maintained for five or six passages in K-SFM medium with 5% FBS. The present study proposed a brief and high-yield protocol for isolation and culture of human cervical epitheliums. Moreover, an infected cell model with HPV-16 E6 gene mediated by lentivirus was established which can do duty for studies in vitro on the carcinogenic mechanism of HR-HPVs.
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Técnicas de Cultivo de Célula/métodos , Cuello del Útero/citología , Células Epiteliales/citología , Lentivirus/metabolismo , Modelos Biológicos , Proteínas Oncogénicas Virales/genética , Proteínas Represoras/genética , Adulto , Proliferación Celular , Forma de la Célula , Células Cultivadas , Colagenasas/metabolismo , Endopeptidasas/metabolismo , Células Epiteliales/metabolismo , Femenino , Humanos , Persona de Mediana Edad , Proteínas Oncogénicas Virales/metabolismo , ARN Mensajero/genética , ARN Mensajero/metabolismo , Proteínas Represoras/metabolismoRESUMEN
Background: The case of "a multimillionaire who was sent to a psychiatric hospital after an argument with his son" has sparked heated debate in the Chinese mainland. This incident is particularly significant as 2023 marks the 10th anniversary of the implementation of the Mental Health Law of the People's Republic of China. The focus of the ongoing debate, as brought to light by the aforementioned case, is centered on the right to refuse treatment for patients with mental disorders. Methods: This paper is a post-hoc study with a systematic analysis of literature and cases. To ascertain the relationship between the right to refuse treatment for patients with mental disorders and the Mental Health Law, the authors identified key information and data from both official government websites and reliable non-governmental information. Result: Both literature and practice have proven that the compulsory hospitalization rule under the Mental Health Law is a denial of the right to refuse treatment for patients who are compulsorily hospitalized. In the absence of changes to the law, compulsory hospitalization will inevitably lead to compulsory treatment in the Chinese mainland. Conclusion: According to the human dignity and self-determination right established in the Constitution of the People's Republic of China, patients who are compulsorily hospitalized have the right to refuse treatment. In the absence of a change in the law, given that no neutral review mechanism has been established for such patients and their treatment in the mainland, setting up an internal review mechanism is a more feasible way of protecting the right to refuse treatment for patients with mental disorders.
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Trastornos Mentales , Negativa del Paciente al Tratamiento , Humanos , China , Trastornos Mentales/terapia , Negativa del Paciente al Tratamiento/legislación & jurisprudencia , Internamiento Obligatorio del Enfermo Mental/legislación & jurisprudencia , Pueblos del Este de AsiaRESUMEN
Nonlinear oscillators can often be used as physical reservoir computers, in which the oscillator's dynamics simultaneously performs computation and stores information. Typically, the dynamic states are multiplexed in time, and then machine learning is used to unlock this stored information into a usable form. This time multiplexing is used to create virtual nodes, which are often necessary to capture enough information to perform different tasks, but this multiplexing procedure requires a relatively high sampling rate. Adaptive oscillators, which are a subset of nonlinear oscillators, have plastic states that learn and store information through their dynamics in a human readable form, without the need for machine learning. Highlighting this ability, adaptive oscillators have been used as analog frequency analyzers, robotic controllers, and energy harvesters. Here, adaptive oscillators are considered as a physical reservoir computer without the cumbersome time multiplexing procedure. With this multiplex-free physical reservoir computer architecture, the fundamental logic gates can be simultaneously calculated through dynamics without modifying the base oscillator.
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A self-learning physical reservoir computer is demonstrated using an adaptive oscillator. Whereas physical reservoir computing repurposes the dynamics of a physical system for computation through machine learning, adaptive oscillators can innately learn and store information in plastic dynamic states. The adaptive state(s) can be used directly as physical node(s), but these plastic states can also be used to self-learn the optimal reservoir parameters for more complex tasks requiring virtual nodes from the base oscillator. Both this self-learning property for reconfigurable computing and the morphable logic gate property of the adaptive oscillator make this an ideal candidate for a multipurpose neuromorphic processor.
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Aims: Mesenchymal stem cells (MSCs) are key components in promoting glioblastoma (GBM) progression. This study aimed to explore new therapeutic targets and related pathogenic mechanisms based on different MSCs infiltration levels in GBM patients. Methods: We estimated the relationship between cell infiltration and prognosis of GBM. Subsequently, key risk genes were identified and prognostic models were constructed by LASSO-Cox analysis. The risk genes were validated by five independent external cohorts, single-cell RNA analysis, and immunohistochemistry of human GBM tissues. TIDE analysis predicted responsiveness to immune checkpoint inhibitors in different risk groups. Results: The MSCs infiltration level was negatively associated with survival in GBM patients. LOXL1, LOXL4, and GUCA1A are key risk genes that promote GBM progression and may act through complex intercellular communication. Conclusion: This research has provided a comprehensive study for exploring the MSCs infiltration environment on GBM progression, which could shed light on novel biomarkers and mechanisms involved in GBM progression.
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The Hopf oscillator is a nonlinear oscillator that exhibits limit cycle motion. This reservoir computer utilizes the vibratory nature of the oscillator, which makes it an ideal candidate for reconfigurable sound recognition tasks. In this paper, the capabilities of the Hopf reservoir computer performing sound recognition are systematically demonstrated. This work shows that the Hopf reservoir computer can offer superior sound recognition accuracy compared to legacy approaches (e.g., a Mel spectrum + machine learning approach). More importantly, the Hopf reservoir computer operating as a sound recognition system does not require audio preprocessing and has a very simple setup while still offering a high degree of reconfigurability. These features pave the way of applying physical reservoir computing for sound recognition in low power edge devices.
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Adaptive oscillators are a subset of nonlinear oscillators that can learn and encode information in dynamic states. By appending additional states onto a classical Hopf oscillator, a four-state adaptive oscillator is created that can learn both the frequency and amplitude of an external forcing frequency. Analog circuit implementations of nonlinear differential systems are usually achieved by using operational amplifier-based integrator networks, in which redesign procedures of the system topology is time consuming. Here, an analog implementation of a four-state adaptive oscillator is presented for the first time as a field-programmable analog array (FPAA) circuit. The FPAA diagram is described, and the hardware performance is presented. This simple FPAA-based oscillator can be used as an analog frequency analyzer, as its frequency state will evolve to match the external forcing frequency. Notably, this is done without any analog-to-digital conversion or pre-processing, making it an ideal frequency analyzer for low-power and low-memory applications.
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BACKGROUND: Cervical cancer is the second most common cancer among women worldwide. With the introduction of organized cervical cytological screening programs, the incidence of cervical cancer has been dramatically reduced. OBJECTIVES: This study aimed to determine the new technology that can potentially afford unique advantages for cervical cancer screening. METHODS: Cervical specimens collected in PreservCyt were processed for ThinPrep cytological test, the new technology test and human papillomavirus detection. RESULTS: The concordance between the new technology and ThinPrep cytological test was 96.34%, with 931 cases positive and 148 cases negative with both tests (κ = 0.857). The sensitivity and the specificity of the new technology were 99.04% (931/940) and 82.22% (148/180), respectively. Youden index was 0.81. The positive predictive value and the negative predictive value were 96.68% (931/963) and 94.27% (148/157), respectively. In the 124 positive cases of the new technology, human papillomavirus DNA test was positive in 109 cases (87.9%) and negative in 15 cases (12.1%). Compared to the histopathological diagnosis, the sensitivity and the negative predictive value of the new technology were 98.57% (69/70) and 95.45% (21/22), respectively. CONCLUSIONS: The screening design will enable evaluation of several competing screening technologies in reducing the incidence of and mortality from cervical cancer. In particular, if the new technology is used as the screening test, it can be a quick screening test and does not depend on the subjective judgment of the doctors. As such, it could potentially afford unique advantages for screening.
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Detección Precoz del Cáncer/métodos , Detección Precoz del Cáncer/tendencias , Displasia del Cuello del Útero/diagnóstico , Neoplasias del Cuello Uterino/diagnóstico , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Automatización de Laboratorios , Citodiagnóstico , Detección Precoz del Cáncer/instrumentación , Femenino , Humanos , Persona de Mediana Edad , Infecciones por Papillomavirus/diagnóstico , Infecciones por Papillomavirus/epidemiología , Neoplasias del Cuello Uterino/epidemiología , Frotis Vaginal , Adulto Joven , Displasia del Cuello del Útero/epidemiologíaRESUMEN
Limit cycle oscillators have the potential to be resourced as reservoir computers due to their rich dynamics. Here, a Hopf oscillator is used as a physical reservoir computer by discarding the delay line and time-multiplexing procedure. A parametric study is used to uncover computational limits imposed by the dynamics of the oscillator using parity and chaotic time-series prediction benchmark tasks. Resonance, frequency ratios from the Farey sequence, and Arnold tongues were found to strongly affect the computation ability of the reservoir. These results provide insights into fabricating physical reservoir computers from limit cycle systems.
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Physical reservoir computing utilizes a physical system as a computational resource. This nontraditional computing technique can be computationally powerful, without the need of costly training. Here, a Hopf oscillator is implemented as a reservoir computer by using a node-based architecture; however, this implementation does not use delayed feedback lines. This reservoir computer is still powerful, but it is considerably simpler and cheaper to implement as a physical Hopf oscillator. A non-periodic stochastic masking procedure is applied for this reservoir computer following the time multiplexing method. Due to the presence of noise, the Euler-Maruyama method is used to simulate the resulting stochastic differential equations that represent this reservoir computer. An analog electrical circuit is built to implement this Hopf oscillator reservoir computer experimentally. The information processing capability was tested numerically and experimentally by performing logical tasks, emulation tasks, and time series prediction tasks. This reservoir computer has several attractive features, including a simple design that is easy to implement, noise robustness, and a high computational ability for many different benchmark tasks. Since limit cycle oscillators model many physical systems, this architecture could be relatively easily applied in many contexts.
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Adaptive oscillators (AOs) are nonlinear oscillators with plastic states that encode information. Here, an analog implementation of a four-state adaptive oscillator, including design, fabrication, and verification through hardware measurement, is presented. The result is an oscillator that can learn the frequency and amplitude of an external stimulus over a large range. Notably, the adaptive oscillator learns parameters of external stimuli through its ability to completely synchronize without using any pre- or post-processing methods. Previously, Hopf oscillators have been built as two-state (a regular Hopf oscillator) and three-state (a Hopf oscillator with adaptive frequency) systems via VLSI and FPGA designs. Building on these important implementations, a continuous-time, analog circuit implementation of a Hopf oscillator with adaptive frequency and amplitude is achieved. The hardware measurements and SPICE simulation show good agreement. To demonstrate some of its functionality, the circuit's response to several complex waveforms, including the response of a square wave, a sawtooth wave, strain gauge data of an impact of a nonlinear beam, and audio data of a noisy microphone recording, are reported. By learning both the frequency and amplitude, this circuit could be used to enhance applications of AOs for robotic gait, clock oscillators, analog frequency analyzers, and energy harvesting.
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Simulación por Computador , Diseño de Equipo , Modelos Teóricos , RobóticaRESUMEN
Cervical cancer is the fourth most common female cancer worldwide. Long non-coding RNAs (lncRNAs), such as SOX21-AS1, play pivotal roles in the progression and metastasis of cancer. We previously described that SOX21-AS1 was hypomethylated in cervical cancer (CC) and aimed to further explore the relationship between methylation of the SOX21-AS1 promoter and CC using clinical cervical samples. Pyrosequencing was performed to detect the methylation status of the SOX21-AS1 promoter in 33 cervical specimens. Additionally, expression levels of related genes in 43 clinical cervical specimens were measured using quantitative real-time PCR (qRT-PCR). The SOX21-AS1 promoter was significantly hypomethylated in CC (P < 0.01). SOX21-AS1 hypomethylation was also significantly associated with an advanced Federation of Gynecology and Obstetrics (FIGO) stage (P < 0.01). The expression levels of SOX21-AS1 and SOX21 were noted to be higher in cancer vs. normal cervix (all P < 0.001). Moreover, the expression of SOX21-AS1 was positively correlated with SOX21 in all samples (r = 0.891, P < 0.001). Methylation statue of the SOX21-AS1 promoter region was negatively correlated with the expression levels of SOX21-AS1 and SOX21 (SOX21-AS1, r = - 0.628; SOX21, r = - 0.648; both P < 0.001). The methylation status of SOX21-AS1 displayed promising diagnostic potential for CC, exhibiting good sensitivity (100.0%) and specificity (69.2%), with an area under the curve of 0.846. In addition, bioinformatic analyses identified a potential link between SOX21-AS1 and the Wnt signaling pathway. Furthermore, methylation status of SOX21-AS1 was negatively correlated with ß-catenin/c-myc/cyclin D1 mRNA levels (rs = - 0.529, - 0.462 ,and - 0.383, respectively, P < 0.05). Our findings illuminated that lncRNA SOX21-AS1 showed hypomethylation in cervical cancer and SOX21-AS1 could serve as a novel biomarker for CC diagnosis or a potential therapeutic target.
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Biomarcadores de Tumor/genética , Metilación de ADN , Regulación Neoplásica de la Expresión Génica , Regiones Promotoras Genéticas , ARN Largo no Codificante/genética , Neoplasias del Cuello Uterino/genética , Adulto , Anciano , Biomarcadores de Tumor/metabolismo , Ciclina D1/genética , Ciclina D1/metabolismo , Femenino , Humanos , Persona de Mediana Edad , Proteínas Proto-Oncogénicas c-myc/genética , Proteínas Proto-Oncogénicas c-myc/metabolismo , ARN Largo no Codificante/metabolismo , Neoplasias del Cuello Uterino/metabolismo , Neoplasias del Cuello Uterino/patología , Vía de Señalización Wnt/genética , beta Catenina/genética , beta Catenina/metabolismoRESUMEN
AIMS: Cervical cancer seriously affects women's health. The function of methylated alterations in the long non-coding RNAs (lncRNAs) promote the progression and metastasis of cancer. Our study aims to identify the functional effects of lncRNA methylation in cervical carcinogenesis. MAIN METHODS: Genome-wide DNA methylation of 6 samples was assessed using the Illumina Infinium MethylationEPIC BeadChip. RNA sequencing (RNA-seq) data and survival follow-up time of 307 samples from The Cancer Genome Atlas (TCGA) dataset were enrolled in this study. The statistical analysis and graphical work were mainly realized by R language. KEY FINDINGS: Methylation map identified 3962 hypermethylated CpG sites and 4484 hypomethylated CpG sites in cervical cancer (|Δß|â¯≥â¯0.20). Bioinformatic analysis of the lncRNA expression identified 363 upregulated and 664 downregulated lncRNAs with log2 (fold change)â¯≥â¯1.00 in squamous cervical carcinoma (SCC) samples. Weighted gene co-expression network analysis (WGCNA) and Venn diagram revealed that lncRNA MAGI2 antisense RNA 3 (lncRNA MAGI2-AS3), lncRNA WT1 antisense RNA (lncRNA WT1-AS) and lncRNA SOX21 antisense divergent transcript 1 (lncRNA SOX21-AS1) were important methylation changed lncRNAs. Kaplan-Meier survival curves showed only lncRNA SOX21-AS1 had clinical prognostic value in cervical cancer. Gene set enrichment analysis (GSEA) suggest that lncRNA SOX21-AS1 involve in the multiple cellular processes and might significantly suppress cervical tumorigenesis. SIGNIFICANCE: These insights into the functional role of lncRNA SOX21-AS1 DNA methylome alterations in cervical cancer might promote clinically new applicable in diagnosis and prognosis.
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Biomarcadores de Tumor/metabolismo , Carcinoma de Células Escamosas/patología , Metilación de ADN , Regulación Neoplásica de la Expresión Génica , Redes Reguladoras de Genes , ARN Largo no Codificante/genética , Neoplasias del Cuello Uterino/patología , Adulto , Biomarcadores de Tumor/genética , Carcinoma de Células Escamosas/genética , Estudios de Casos y Controles , Proliferación Celular , Femenino , Humanos , Persona de Mediana Edad , Pronóstico , Tasa de Supervivencia , Células Tumorales Cultivadas , Neoplasias del Cuello Uterino/genéticaRESUMEN
BACKGROUND: The aim of this study was to investigate the methylation status of E2BSs in the HPV 16 long control region (LCR) in clinical cervical samples. METHODS: Methylation status of the four E2BSs in 43 clinical cervical samples with HPV 16 infection was quantitatively detected using pyrosequencing. Meanwhile, Quantivirus® HPV E6/E7 RNA 3.0 assay (bDNA) was used to detect E6/E7 mRNA levels in the corresponding specimens. RESULTS: Our results showed that methylation status of E2BS1, 2 and 4 sites in high-grade squamous intraepithelial lesions (HSIL) and cervical cancer were significantly higher than that of asymptomatic HPV 16 infection and low-grade squamous intraepithelial lesions (LSIL) (all Pâ¯<â¯.05). Furthermore, methylation status of HPV 16 E2BS1 and 2 was positively correlated with E6/E7 mRNA levels (rsâ¯=â¯0.529 and 0.512 respectively, Pâ¯<â¯.01). Receiver operating characteristic curve analysis was used to compare the diagnostic performance of E2BSs methylation. When the Youden index was the maximum value, the methylation level of E2BS1 and E2BS2 all demonstrated optimum diagnostic sensitivity of 77.8%, and specificity of 80% and 92%, respectively. CONCLUSIONS: The methylation status of E2BS1 and 2 may have utility as diagnostic markers for the severity of cervical lesions in the future.
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Papillomavirus Humano 16/genética , Infecciones por Papillomavirus/genética , Displasia del Cuello del Útero/genética , Neoplasias del Cuello Uterino/genética , Adulto , Anciano , Sitios de Unión , Femenino , Humanos , Metilación , Persona de Mediana Edad , Infecciones por Papillomavirus/diagnóstico , Estudios Prospectivos , ARN Mensajero/genética , Neoplasias del Cuello Uterino/diagnóstico , Displasia del Cuello del Útero/diagnósticoRESUMEN
An early prediction of prognosis for patients with colorectal liver metastasis (CRLM) may help us determine treatment strategies. Liver function reflects the effect of the overall metastatic burden. We investigated the prognostic value of liver function in CRLM patients. In our study, patients with abnormal LFTs (liver function tests) had a poorer prognosis than did those with normal LFTs (P < 0.05). A multivariate analysis revealed that LFTs was an independent prognostic factor for CRLM. For those patients with abnormal LFTs, novel prognostic contour maps were generated using LFTs, and no positive correlation exists between the values of survival duration and abnormal LFTs. Additionally, the MTVR (metastatic tumor volume ratio) was measured directly by magnetic resonance imaging and was shown to be highly correlated to LFTs by a Pearson correlation analysis. A multivariate logistic regression analysis also demonstrated that the MTVR and hepatectomy were independently predictive of abnormal LFTs. The space-occupying effect of metastatic lesions can cause abnormal LFTs, resulting in a poor prognosis. Biochemical analyses of LFTs at the initial diagnosis of CRLM enable the stratification of patients into low- and high-risk groups; it may help clinicians determine promising treatment strategies.
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Neoplasias Colorrectales , Neoplasias Hepáticas , Hígado , Adulto , Anciano , Neoplasias Colorrectales/metabolismo , Neoplasias Colorrectales/mortalidad , Neoplasias Colorrectales/patología , Supervivencia sin Enfermedad , Femenino , Humanos , Hígado/metabolismo , Hígado/patología , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/mortalidad , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/secundario , Masculino , Persona de Mediana Edad , Metástasis de la Neoplasia , Tasa de SupervivenciaRESUMEN
BACKGROUND: Hilar cholangiocarcinomas are malignant tumors with a poor prognosis. An early prediction of prognosis for patients may help us determine treatment strategies. Aquaporin 1 is a cell membrane channel involved in water transport, cell motility, and proliferation. Increasing evidences showed that aquaporin 1 played a role in tumor prognosis and diagnosis. The purpose of this study is to evaluate the role of aquaporin 1 in hilar cholangiocarcinoma. METHODS: Here, we analyzed messenger RNA expression data of genes function as bile secretion in a data set of 169 samples using the R2 bioinformatic platform ( http://r2.amc.nl ). Quantitative polymerase chain reaction was performed to verify the gene expression in 17 hilar cholangiocarcinoma samples. Immunohistochemistry was also performed in a series of specimens from 62 hilar cholangiocarcinoma tissues, and its clinical significance was assessed by clinical correlation and Kaplan-Meier analyses. RESULTS: All data were analyzed using the R2 web application, aquaporin 1 was selected for further analysis. The significant expression variation of aquaporin 1 among 17 cases with cholangiocarcinoma was also found using quantitative polymerase chain reaction. The expression level of aquaporin 1 protein significantly correlated with tumor-node-metastasis stage ( P = .002) and overall survival time ( P = .010). Higher aquaporin 1 expression indicated poor prognostic outcomes ( P <.05, log-rank test). Multivariate analysis also showed strong aquaporin 1 protein expression was an independent adverse prognosticator in hilar cholangiocarcinoma ( P = .002). CONCLUSION: This study highlighted the prognostic value of aquaporin 1 in hilar cholangiocarcinoma. Strong aquaporin 1 expression predicts poor survival, regardless of pathological features. Immunohistochemical detection of aquaporin 1, as a prognostic marker, may contribute to predicting clinical outcome for patients with hilar cholangiocarcinoma.
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Acuaporina 1/metabolismo , Neoplasias de los Conductos Biliares/metabolismo , Tumor de Klatskin/metabolismo , Adulto , Anciano , Acuaporina 1/genética , Neoplasias de los Conductos Biliares/mortalidad , Neoplasias de los Conductos Biliares/patología , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Femenino , Humanos , Estimación de Kaplan-Meier , Tumor de Klatskin/mortalidad , Tumor de Klatskin/secundario , Metástasis Linfática , Masculino , Persona de Mediana Edad , Pronóstico , Modelos de Riesgos Proporcionales , TranscriptomaRESUMEN
OBJECTIVE: To compare E6/E7 mRNA and HPV DNA assays for evaluating women with atypical cells of undetermined significance (ASCUS). METHODS: The present prospective study enrolled patients with ASCUS undergoing HPV testing at Third Affiliated Hospital of Zhengzhou University, China, between September 1, 2013, and January 31, 2016. Patients with positive HPV DNA test results underwent screening by E6/E7 mRNA assay, and the accuracy of HPV DNA and E6/E7 mRNA testing were compared, with histology used for definitive diagnoses. RESULTS: In total, 591 patients with ASCUS underwent HPV DNA screening, with 455 and 136 having positive and negative results, respectively; 252 patients with positive results and 66 with negative results underwent biopsy and histology testing and were included in the study. The sensitivity of the E6/E7 mRNA assay was similar to that of HPV DNA testing (88.2%, 95% confidence interval [CI] 77.6-94.4 vs 90.7%, 95%CI 81.2-95.9; P=0.636) for the detection of cervical intraepithelial neoplasia grade 2+, and the specificity was higher (36.4%, 95%CI 29.6-43.9 vs 24.3%, 95%CI 19.1-30.3; P=0.006). The area under the receiver operating characteristic curve was greater for E6/E7 mRNA testing compared with HPV DNA testing (0.658 vs 0.588). CONCLUSION: The higher specificity of the E6/E7 mRNA assay means it could be a promising technique in the management of women with ASCUS.
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ADN Viral/análisis , Papillomaviridae/genética , Infecciones por Papillomavirus/virología , ARN Viral/análisis , Displasia del Cuello del Útero/virología , Adulto , China , Progresión de la Enfermedad , Femenino , Humanos , Infecciones por Papillomavirus/patología , Estudios Prospectivos , Curva ROC , Sensibilidad y Especificidad , Salud de la Mujer , Displasia del Cuello del Útero/patologíaRESUMEN
AIM: To identify a small, clinically applicable immunohistochemistry (IHC) panel that could be combined with magnetic resonance imaging (MRI)-detected extramural vascular invasion (EMVI) for assessment of prognosis concerning the non-advanced rectal cancer patients prior to operation. METHODS: About 329 patients with pathologically confirmed rectal carcinoma (RC) were screened in this research, all of whom had been examined via an MRI and were treatment-naïve from July 2011 to July 2014. The candidate proteins that were reported to be altered by RC were examined in tissues by IHC. All chosen samples were adopted from the fundamental cores of histopathologically confirmed carcinomas during the initial surgeries. RESULTS: Of the three proteins that were tested, c-MYC, PCNA and TIMP1 were detected with relatively significant expression in tumors, 35.9%, 23.7% and 58.7% respectively. The expression of the three proteins were closely connected with prognosis (P = 0.032, 0.003, 0.021). The patients could be classified into different outcome groups according to an IHC panel (P < 0.01) via these three proteins. Taking into consideration known survival covariates, especially EMVI, the IHC panel served as an independent prognostic factor. The EMVI combined with the IHC panel could categorize patients into different prognostic groups with distinction (P < 0.01). CONCLUSION: These studies argue that this three-protein panel of c-MYC, PCNA, coupled with TIMP1 combined with MRI-detected EMVI could offer extra prognostic details for preoperative treatment of RC.