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We intend to evaluate the importance of N7 -methylguanosine (m7G) for the prognosis of breast cancer (BC). We gained 29 m7G-related genes from the published literature and among them, 16 m7G-related genes were found to have differential expression. Five differentially expressed genes (CYFIP1, EIF4E, EIF4E3, NCBP1 and WDR4) were linked to overall survival. This suggests that m7G-related genes might be prognostic or therapeutic targets for BC patients. We put the five genes to LASSO regression analysis to create a four-gene signature, including EIF4E, EIF4E3, WDR4 and NCBP1, that divides samples into two risky groups. Survival was drastically worsened in a high-risk group (p < 0.001). The signature's predictive capacity was demonstrated using ROC (10-year AUC 0.689; 10-year AUC 0.615; 3-year AUC 0.602). We found that immune status was significantly different between the two risk groups. In particular, NCBP1 also has a poor prognosis, with higher diagnostic value in ROC. NCBP1 also has different immune states according to its high or low expression. Meanwhile, knockdown of NCBP1 suppresses BC malignancy in vitro. Therefore, m7G RNA regulators are crucial participants in BC and four-gene mRNA levels are important predictors of prognosis. NCBP1 plays a critical target of m7G mechanism in BC.
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Neoplasias de la Mama , Guanosina , Femenino , Humanos , Biomarcadores , Neoplasias de la Mama/genética , Factor 4E Eucariótico de Iniciación , Proteínas de Unión al GTP , Guanosina/análogos & derivados , Complejo Proteico Nuclear de Unión a la Caperuza/metabolismo , PronósticoRESUMEN
BACKGROUND: Recent studies have demonstrated that copper (Cu) plays an important role in the progression of tumor diseases. Metastasis associated with colon cancer protein 1 (MACC1) promotes the transcription and expression of various tumor-related genes. Cytochrome c oxidase (COX) 19, present in the cytoplasm and intermembrane space of mitochondria, may transport Cu within the mitochondria. However, the mechanism through which MACC1 regulates the Cu homeostasis mediated by COX19 remains unclear. OBJECTIVES: The aim of this study was to elucidate the mechanism through which MACC1 initiates the transcription and expression of COX19, and promotes malignant behavior in tumor cells. METHODS: Immunohistochemistry, western blotting, and real-time polymerase chain reaction (PCR) analyses were conducted to analyze the expression of MACC1 and COX19 proteins and genes in tumor and normal tissues. RNA-chromatin immunoprecipitation was used to detect the transcriptional initiation of COX19 by MACC1. The effects of MACC1 and COX19 on mitochondrial activity were determined using an ATP assay kit and Cytochrome c Oxidase Assay Kit. A Cell Counting Kit-8 kit was used to detect the effect of high-dose Cu or overexpression of MACC1 and COX19 on tumor cell proliferation. A xenograft mouse model was used to analyze the effect of the COX19 overexpression on the malignant behavior of the tumors. RESULTS: Cu enhanced the proliferation, invasion, and migration and inhibited apoptosis of SW480 cells. MACC1 was highly expressed in colorectal cancer tissues and activated the expression of COX19 by binding to its promoter region of COX19. The overexpression of COX19 increased mitochondrial Cu content and enhanced the activity of mitochondrial COX and ATP content, and inhibited apoptosis, promoted tumor growth of mice. CONCLUSIONS: Our results indicate that COX19 functions as a target gene of MACC1 and regulates mitochondrial activity and promotes the progression of colorectal cancer. MACC1/COX19 may provide a novel therapeutic target for colorectal cancer.
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Neoplasias del Colon , Neoplasias Colorrectales , Animales , Humanos , Ratones , Adenosina Trifosfato/metabolismo , Línea Celular Tumoral , Proliferación Celular , Neoplasias del Colon/metabolismo , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/patología , Cobre/metabolismo , Complejo IV de Transporte de Electrones/genética , Complejo IV de Transporte de Electrones/metabolismo , Regulación Neoplásica de la Expresión Génica , Mitocondrias/metabolismo , Transactivadores/genética , Transactivadores/metabolismoRESUMEN
Androgen deprivation therapy is a common treatment method for metastatic prostate cancer through lowering androgen levels; however, this therapy frequently leads to the development of castration-resistant prostate cancer (CRPC). This is attributed to the activation of the androgen receptor (AR) signaling pathway. Current treatments targeting AR are often ineffective mostly due to AR gene overexpression and mutations, as well as the presence of splice variants that accelerate CRPC progression. Thus there is a critical need for more specific medication to treat CRPC. Small interfering RNAs have shown great potential as a targeted therapy. This review discusses prostate cancer progression and the role of AR signaling in CRPC, and proposes siRNA-based targeted therapy as a promising strategy for CRPC.
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Neoplasias de la Próstata Resistentes a la Castración , Masculino , Humanos , Neoplasias de la Próstata Resistentes a la Castración/terapia , Neoplasias de la Próstata Resistentes a la Castración/tratamiento farmacológico , Receptores Androgénicos/genética , Receptores Androgénicos/metabolismo , Andrógenos , Antagonistas de Andrógenos/uso terapéutico , ARN Interferente Pequeño/genética , ARN Interferente Pequeño/uso terapéutico , Transducción de SeñalRESUMEN
Breast cancer is considered the most prevalent malignancy due to its high incidence rate, recurrence, and metastasis in women that makes it one of the deadliest cancers. The current study aimed to predict the genes associated with the recurrence and metastasis of breast cancer and to validate their effect on MDA-MB-231 cells. Through the bioinformatics analysis, the transcription factor 7 cofactor (MLLT11) as the target gene was obtained. MLLT11-specific siRNA was synthesized and transfected into MDA-MB-231 cells. The results demonstrated that the siRNA significantly reduced the MLLT11 mRNA levels. Moreover, cell migration and invasion, as well as the protein levels of phosphatidylinositol 3-kinase (PI3K), AKT, matrix metalloproteinase (MMP) 2, and MMP9, were significantly lower in the groups treated with siRNA while the apoptosis was augmented. Collectively, MLLT11 siRNA elicited ameliorative properties on breast cancer cells, possibly via the inhibition of the PI3K/AKT signaling pathway.
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Neoplasias de la Mama , Femenino , Humanos , Apoptosis , Neoplasias de la Mama/genética , Neoplasias de la Mama/patología , Línea Celular Tumoral , Proliferación Celular , Células MDA-MB-231 , Invasividad Neoplásica/patología , Proteínas de Neoplasias/farmacología , Fosfatidilinositol 3-Quinasas/genética , Fosfatidilinositol 3-Quinasas/metabolismo , Proteínas Proto-Oncogénicas/metabolismo , Proteínas Proto-Oncogénicas c-akt/genética , Proteínas Proto-Oncogénicas c-akt/metabolismo , ARN Interferente Pequeño/genética , ARN Interferente Pequeño/farmacología , Factores de TranscripciónRESUMEN
The aim of this study was to investigate the role of circRNA insulin growth factor 1 receptor (circ-IGF1R) in colorectal cancer (CRC). Glycolytic metabolism was analyzed by glucose uptake and lactate production using the corresponding kits. The protein levels were determined using Western blot. The effect of circ-IGF1R on CRC in vivo was explored by xenograft experiment in mice. Circ-IGF1R was up-regulated in CRC tissues and cells. Knockdown of circ-IGF1R inhibited proliferation, migration, invasion and glycolysis but induced apoptosis of CRC cells. Circ-IGF1R interacted with miR-362-5p and miR-362-5p inhibitor attenuated the anti-tumor effects of circ-IGF1R downregulation on CRC cells. HMGB3 acted as a downstream target for miR-362-5p, and circ-IGF1R facilitated the malignant behaviors of CRC cells by regulating HMGB3. Circ-IGF1R activated the Wnt/ß-catenin pathway via targeting miR-362-5p/HMGB3 axis. Tumor growth in vivo was reduced after knockdown of circ-IGF1R. Circ-IGF1R might be a novel biomolecular target for CRC diagnosis and treatment.
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Neoplasias Colorrectales , MicroARNs , ARN Circular , Animales , Humanos , Ratones , beta Catenina/genética , Línea Celular Tumoral , Proliferación Celular , Neoplasias Colorrectales/genética , Ácido Láctico , MicroARNs/genética , Receptor IGF Tipo 1/genética , Transducción de Señal , Factores de Transcripción , ARN Circular/genética , ARN Circular/metabolismo , Proteína HMGB3/genética , Proteína HMGB3/metabolismoRESUMEN
Lymphoblastic lymphoma is an aggressive subtype of non-Hodgkin lymphoma. Identification of prognostic factors for these patients, especially for patients with T-cell lymphoblastic lymphoma (T-LBL), remains a challenge. This is largely due to the relative rarity of the disease and lack of adequate samples for biological research. T-LBL is more common in Asia than in Western countries. In an attempt to explore novel prognostic markers for T-LBL, we conducted retrospective study of archived diagnostic specimens from 57 Chinese patients with well-defined diagnosis of T-LBL. Using quantitative real-time reverse transcription-PCR, we analyzed miR-17 and miR-19 expression levels in formalin-fixed and paraffin-embedded lymph node specimens from these patients, together with reactive lymph node controls. We correlated molecular findings to patients' immunophenotype and clinical follow-up information. MYC protein expression was also evaluated in these patients. We found that miR-17 and miR-19 levels were concordant and upregulated in T-LBL in comparison with controls. Statistical analysis showed that higher expression of miR-17 and miR-19, and positive MYC protein results were associated with a shorter overall survival of T-LBL. In addition, miR-17 and miR-19 appeared to be independent prognostic factors for T-LBL. We demonstrate here that upregulation of miR-17 and miR-19 correlates with poor clinical outcome of T-LBL, indicating that miR-17 and miR-19 may be considered as potential unfavorable prognostic markers for T-LBL.
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Biomarcadores de Tumor/genética , Regulación Neoplásica de la Expresión Génica , MicroARNs/genética , Leucemia-Linfoma Linfoblástico de Células T Precursoras/genética , Leucemia-Linfoma Linfoblástico de Células T Precursoras/mortalidad , Adolescente , Adulto , Anciano , Niño , Preescolar , Estudios de Cohortes , Femenino , Humanos , Técnicas para Inmunoenzimas , Hibridación Fluorescente in Situ , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Leucemia-Linfoma Linfoblástico de Células T Precursoras/patología , Pronóstico , Tasa de Supervivencia , Adulto JovenRESUMEN
OBJECTIVE: To study the C-myc gene and protein in T lymphoblastic lymphoma/leukemia (T-LBL/ALL) and its relationship to prognosis. METHODS: 60 cases of T-LBL/ALL with follow-up data were studied by using immunohistochemical EnVision method for CD1a, CD3, εCD3, CD7, CD10, CD34, CD43, CD45RO, CD99, TDT, CD20, CD23, MPO, Ki-67 and C-myc. 20 cases of reactive lymph nodes were selected as normal control group of C-myc gene and protein. Fluorescence in-situ hybridization (FISH) for C-myc gene (located on chromosome8q24) was performed to detect its breakage and gain. RESULTS: Among the 60 cases of T-LBL/ALL, immunohistochemistry results showed:the percentages of tumor cells expression of CD1a, CD3, εCD3, CD7, CD10, CD34, CD43, CD45RO, CD99 and TDT were 38.3% (23/60), 75.0% (45/60), 45.0% (27/60), 95.0% (57/60), 36.7% (22/60), 23.3% (14/60), 60.0% (36/60), 41.7% (25/60), 96.7% (58/60) and 93.3% (56/60). Separately, while CD20, CD23 and MPO were all negative. A figure of Ki-67 expression ≤ 80% was found in 36 cases and > 80% was found in 24 cases. The positive rate of C-myc protein was 66.7% (40/60) in 60 cases of T-LBL/ALL, was 0% (0/20) in 20 cases of reactivated lymphoid tissue (χ² = 26.67, P < 0.05). C-myc protein expression was positively correlated with the mediatinal width and Ki-67 index (P < 0.05). Fluorescence in-situ hybridization results showed that among the 60 cases of T-LBL/ALL, C-myc gene with breakage of 8q24 was detected in 6 cases (10.0%), and gains in 11 cases (18.3%). 20 cases of reactive lymph nodes were not occurred breakage and gains of C-myc gene. It is not significant between C-myc gene and protein expression (P > 0.05). In addition, in 60 cases of T-LBL/ALL, 12(20.0%) cases of C-myc protein and genetic abnormalities coexist. Log-rank analysis results: The prognosis of C-myc protein positive group was worse than negative group (P < 0.05). The relationship of C-myc gene and prognosis was not significant (P > 0.05). C-myc protein and genetic abnormality coexist is related with worse prognosis (P < 0.05). COX analysis results show that the C-myc protein positive group may be a independent poor prognosis factors (P < 0.05). CONCLUSIONS: C-myc may play an important role on the development of T-LBL/ALL. It may be a independent prognosis factors.
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Leucemia-Linfoma Linfoblástico de Células T Precursoras/diagnóstico , Leucemia-Linfoma Linfoblástico de Células T Precursoras/metabolismo , Proteínas Proto-Oncogénicas c-myc/metabolismo , Humanos , Inmunohistoquímica , Hibridación Fluorescente in Situ , Antígenos Comunes de Leucocito , Ganglios Linfáticos/patología , PronósticoRESUMEN
PURPOSE: This study aims to investigate the expression patterns and clinical significance of miR-140-3p and homeobox A9 (HOXA9) in colorectal cancer (CRC) selected by bioinformatic study, while elucidating their potential interplay. METHODS: The microRNA expression profiles of paired colorectal cancer and matched normal tissues were retrieved from the Gene Expression Omnibus Database. Differentially expressed microRNAs and microRNA candidates were filtered and subjected to further analysis. Clinicopathological data, along with paraffin-embedded samples of colorectal tumor tissues were collected to facilitate comprehensive analysis. Expression levels of miR-140-3p and HOXA9 were quantified using qRT-PCR and immunohistochemistry. Survival rates were determined using the Kaplan-Meier method, and the COX regression model was utilized to identify independent prognostic factors that impact the overall prognosis. RESULTS: MiR-140-3p was significantly downregulated in colorectal tumors compared to normal tissue, and HOXA9 was identified as a previously unreported potential downstream target. HOXA9 expression was elevated in tumors compared to normal tissues. Reduced miR-140-3p expression was associated with lymph node metastasis, while high HOXA9 expression correlated with both lymph node metastasis and lympho-vascular invasion. Patients with low miR-140-3p and high HOXA9 expression had a poorer prognosis. HOXA9 was identified as an independent risk factor for CRC patient survival. CONCLUSION: The miR-140-3p-HOXA9 signaling disruption is closely linked to lymph node metastasis and unfavorable prognosis in CRC. This axis shows promise as a clinical biomarker for predicting the CRC patient survival and a potential therapeutic target.
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Neoplasias Colorrectales , MicroARNs , Humanos , Genes Homeobox , Relevancia Clínica , Metástasis Linfática , MicroARNs/genética , Neoplasias Colorrectales/genéticaRESUMEN
Introduction: GRHL1 belongs to the family of Grainyhead-like (GRHL). Previous studies have shown that dysregulation of growth and survival pathways is associated with the GRHL family of gene cancers. Immunotherapy with checkpoint inhibitors has changed the treatment paradigm for many tumors, including endometrial cancer (EC). However, the effect of GRHL1 on immunotherapy in EC and its relationship with immune cell infiltration are poorly understood. Methods: Differential expression of GRHL1 between EC and normal EC tissues was analyzed by searching the TCGA database, and the results were verified utilizing immunohistochemistry analyses. Next, the relationship between GRHL1, CD8+ T cells and tumor microenvironment (TME) was also investigated, and the effect of GRHL1 expression on immunotherapy in EC was evaluated. Results: According to the findings, EC tissues had elevated expression levels of GRHL1 relative to normal tissues. Patients with EC who expressed GRHL1 at high levels experienced worse overall survival (OS) and Progression-free survival (PFS) than those whose expression was lower. In addition, GRHL1 expression was negatively correlated with CD8+ T cells, and patients with high GRHL1 expression were less effective in receiving immunotherapy. Conclusion: The expression of GRHL1 was high in EC patients, and high expression of GRHL1 inhibits the proliferation of CD8+ T cells in the tumor microenvironment of EC and affect the efficacy of immunotherapy.
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INTRODUCTION: Cervical cancer (CC) is associated with high morbidity and mortality rates in women. Members of the receptor-interacting protein kinase (RIPK) family are important regulators of inflammation and cell death. However, the characteristics, molecular functions, and expression mechanisms of RIPK1 in CC remain unclear. MATERIAL AND METHODS: To determine whether RIPK1 can be used for targeted therapy of CC, we assessed the clinical importance, biological function, and potential impact of RIPK1 in CC in 50 patients with CC. We utilized immunohistochemical staining, transfection, western blotting, cell counting kit-8 assay, colony formation assay, and wound healing assays among others, to elucidate the role of RIPK1 in CC. RESULTS: RIPK1 expression was higher in tumor tissues than in paracancerous tissues. Poor prognosis of CC was linked to RIPK1 upregulation. Furthermore, silencing RIPK1 significantly inhibited the proliferation, migration, and invasion of CC cells in vitro. We also established that RIPK1 increased cell migration, invasion, and multiplication by regulating nuclear factor kappa-B (NF-κB) and tumor necrosis factor (TNF). DISCUSSION: RIPK1 activates NF-κB and regulates TNF release to enhance the proliferation and spread of CC cells while suppressing their apoptosis. Therefore, RIPK1 plays a key role in the formation and progression of CC and is a potential target for CC treatment.
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Objectives: Patient-derived xenograft (PDX) model becomes a more and more important tool for tumor research. This study aimed to establish a colorectal cancer PDX model and verify its applicability. Materials and Methods: Fresh human colorectal cancer tissue was surgically removed and subcutaneously inoculated into immunodeficient mice to establish the PDX model. Hematoxylin and eosin (HE) staining and immunohistochemical staining were used to evaluate the model. The successful PDX model was selected to study the efficacy of capecitabine in treating colorectal cancer. Results: HE staining showed that the PDX mice model of colorectal cancer could preserve the histological characteristics of the primary tumor. Immunohistochemistry staining showed α-fetoprotein (AFP), carcinoembryonic antigen (CEA), and E-cadherin were strongly positively expressed in primary human and PDX tumor tissues, with a high degree of similarity. Capecitabine significantly inhibited PDX tumor growth and reduced the expression of AFP and CEA proteins in the tumor tissues (all P s<0.05). Conclusion: We successfully established a colorectal cancer PDX model, and the PDX model could retain the histological and biological characteristics of the primary tumor. Using this PDX model, we revealed that capecitabine at a dose of 300-400 mg/kg can effectively treat colorectal cancer, and no significant difference in toxicity was found among different dose groups. The current work provides a feasible framework for establishing and validating the PDX tumor model to better facilitate the evaluation of drug efficacy and safety.
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Background: Cervical cancer is one of the most common types of carcinoma in women and has high morbidity and mortality rates worldwide. Recurrent and metastatic disease remains difficult to treat. Receptor interacting protein kinase 1 (RIPK1) is a key molecule in mediating apoptosis, necroptosis, and inflammatory pathways downstream of death receptors and pattern recognition receptors. This study sought to explore the clinicopathological and prognosis significance of RIPK1 expression in cervical squamous cell carcinoma (CSCC). Methods: The data of 100 CSCC patients who underwent curative surgery from 2019 to 2020 were retrospectively included in this study. We collected the clinicopathological information of the patients and detected RIPK1 protein expression using immunohistochemistry. The Chi-square test and a 1-way analysis of variance were used to make comparisons between groups stratified by RIPK1 expression. A Pearson linear correlation analysis was used to evaluate the association between RIPK1 expression and the clinicopathological characteristics of the patients. A Cox regression analysis and Kaplan-Meier curves were used to analyze overall survival (OS) and progression-free survival (PFS). A multivariable regression analysis was conducted to identify the risk factors for an impaired prognosis in CSCC. Results: RIPK1 was found to be overexpressed in the CSCC tissues. RIPK1 expression was significantly associated with age, the preoperative serum squamous cell carcinoma antigen (SCC-Ag) level, lymph node metastasis, invasion depth, International Federation of Gynecology and Obstetrics (FIGO) stage, tumor size, PFS, and OS (P<0.05). The PFS and OS differed significantly among patients with RIPK1 expression (P<0.05). The multivariate analysis showed that RIPK1 was not independent risk factors for PFS and OS in CSCC patients (P>0.05). Conclusions: The expression of RIPK1 was significantly upregulated in CSCC and was associated with the clinicopathological features of CSCC. RIPK1 might serve as a novel marker that can be used to predict the prognosis of CSCC patients and as a biological target for the treatment of CSCC.
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Chemotherapy represents a major type of clinical treatment against colorectal cancer (CRC). Aberrant drug efflux mediated by transporters acts as a key approach for tumor cells to acquire chemotherapy resistance. Increasing evidence implies that tumor-associated macrophages (TAMs) play a pivotal role in both tumorigenesis and drug resistance. Nevertheless, the specific mechanism through which TAMs regulate drug efflux remains elusive. Here, we discovered that TAMs endow CRC cells with resistance to 5-fluorouracil (5-FU) treatment via a cell-cell interaction-mediated MRP1-dependent drug efflux process. Mechanistically, TAM-secreted C-C motif chemokine ligand 17 (CCL17) and CCL22, via membrane receptor CCR4, activated the PI3K/AKT pathway in CRC tumor cells. Specifically, phosphorylation of AKT inactivated IP3R and induced calcium aggregation in the ER, resulting in the activation of ATF6 and upregulation of GRP78. Accordingly, excessive GRP78 can interact with MRP1 and promote its translocation to the cell membrane, causing TAM-induced 5-FU efflux. Taken together, our results demonstrated that TAMs promote CRC chemotherapy resistance via elevating the expression of GRP78 to promote the membrane translocation of MRP1 and drug efflux, providing direct proof for TAM-induced drug resistance.
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Neoplasias Colorrectales , Chaperón BiP del Retículo Endoplásmico , Humanos , Macrófagos Asociados a Tumores , Fosfatidilinositol 3-Quinasas , Proteínas Proto-Oncogénicas c-akt , Fluorouracilo/farmacología , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/genética , Factor de Transcripción Activador 6 , Receptores CCR4 , Quimiocinas CXCRESUMEN
PURPOSE: Cell-free circulating tumor DNA (ctDNA) in plasma enables rapid and repeat testing of actionable mutations. Next-generation sequencing (NGS) is an attractive platform for multiplex sequencing capabilities compared to traditional methods such as PCR. The purpose of this study is to evaluate the value of the NGS-based ctDNA assay and to identify the genomic alteration profile of ctDNA in real-world Chinese non-small cell lung (NSCLC) patients. METHODS: In total, 294 Chinese patients with pathological diagnosis of Phase III-IV NSCLC were enrolled. 3-4 mL peripheral blood was collected and NGS-based analysis was carried out using a 20-gene panel. The analytical sensitivity and specificity of ctDNA NGS-based assay was validated using droplet digital PCR (ddPCR). RESULTS: We have tested 570 sites from 286 samples using ddPCR, which included 108 positive sites and 462 negative sites from NGS results, and the concordance rate was 99.8% (418/419) for single-nucleotide variants (SNVs) and 96.7% (146/151) for insertions and deletions (InDels). The most frequent genes were TP53 (32%), EGFR (31.97%), KRAS (6.46%), PIK3CA (4.76%), and MET (4.08%). Exon 19 deletion (19del) was the most common alteration in EGFR and G12C was the most common alteration in KRAS. Furthermore, the detection rate of TP53 was higher in the male and patients with squamous cell carcinoma. We also found the prevalence of TP53 in L858R was higher than in 19del (61.29% vs. 40%; p = 0.1115). CONCLUSION: The results indicate that the results of NGS-based ctDNA assay are highly consistent with ddPCR. In Chinese NSCLC patients, TP53 mutation was more frequently associated with male and squamous cell carcinoma. The prevalence of concomitant mutations in L858R may be different from that in 19del.
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Carcinoma de Pulmón de Células no Pequeñas , Carcinoma de Células Escamosas , ADN Tumoral Circulante , Neoplasias Pulmonares , Humanos , Masculino , Biomarcadores de Tumor/genética , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/diagnóstico , Carcinoma de Células Escamosas/genética , ADN Tumoral Circulante/genética , Pueblos del Este de Asia , Receptores ErbB/genética , Genómica , Secuenciación de Nucleótidos de Alto Rendimiento/métodos , Neoplasias Pulmonares/patología , Mutación , Proteínas Proto-Oncogénicas p21(ras)/genética , FemeninoRESUMEN
This paper presents a task prioritization strategy based on a generic underwater task goal classification transformation for multitasking underwater operational tasks: attitude control, floating manipulation, collision-free motion, especially optimizing trajectory of the end-effector of an underwater vehicle manipulator system (UVMS) in a complex marine environment. The design framework aims to divide the complex underwater operational tasks into UVMS executable generic task combinations and optimize the resource consumption during the whole task. In order to achieve the corresponding underwater task settings, the system needs to satisfy different task scheduling structures. We consider the actual application scenarios of the operational goals and prioritize and define each category of task hierarchy accordingly. Multiple tasks simultaneously enable fast adaptation to UVMS movements and planning to complete UVMS autonomous movements. Finally, an underwater vehicle manipulator system implements the task prioritization planning framework for a practical scenario with different constraints on different goals. We quickly and precisely realize the interconversion of different tasks under goal constraints. The autonomous motion planning and real-time performance of UVMS are improved to cope with the increasing operational task requirements and the complex and changing practical engineering application environments.
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Cervical cancer is one of the most common malignancies in women with high morbidity and mortality. Human papillomavirus (HPV) infection is the primary cause of cervical cancer, of which HPV 16 is the predominant. Early detection and effective treatment of cervical precancerous lesions are the key to preventing cervical cancer. Vitamin D receptor (VDR) gene polymorphism is considered to be an important cause of cancer development. Here, we studied the association of VDR polymorphisms (FOKI, BsmI, ApaI, and TaqI) in HPV16-positive cervical intraepithelial neoplasia (CIN)2+ patients. HPV16-positive patients who visited the Colposcopy Clinic of Obstetrics and Gynecology, the Second Hospital of Shanxi Medical University for biopsy due to abnormal HPV and/or Thinprep cytologic test (TCT) from September 1, 2020 to October 1, 2021 were grouped by pathological results. The fasting blood samples were collected and VDR polymorphisms were detected using TaqMan fluorescent probes, and the three sites of BsmI-ApaI-TaqI were subjected to haplotype analysis. FOKI ff genotype (OR = 2.01; 95% CI = 1.12 - 3.59; p = 0.019) and f allele (OR = 1.48; 95% CI = 1.10 - 1.98; p = 0.009) were found to be associated with the risk of CIN2+. TaqI Tt genotype (OR = 2.03; 95% CI = 1.20 - 3.43; p = 0.008), tt genotype (OR = 2.09; 95% CI = 1.09 - 4.02; p = 0.028), and t allele (OR = 1.35; 95% CI = 1.01 - 1.80; p = 0.041) were associated with the risk of CIN2+. No haplotype was associated with CIN2+ risk. According to the results, FOKI and TaqI polymorphisms are associated with CIN2+ risk.
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Infecciones por Papillomavirus , Neoplasias del Cuello Uterino , Embarazo , Humanos , Femenino , Receptores de Calcitriol/genética , Neoplasias del Cuello Uterino/genética , Polimorfismo Genético/genéticaRESUMEN
Cyclin-dependent kinases (CDKs) play an important role in cell division. Given that abnormal cell proliferation caused by dysregulation of cell division is one of the major causes of endometrial cancer (EC), it is important to elucidate the role of CDK family genes in the diagnosis and prognosis of EC. In this study, The Cancer Genome Atlas (TCGA) database was used to analyze the frequency of copy number variations and somatic mutations in 26 CDK family genes. Subsequently, the expression of these genes in EC was assessed, and their relationship with overall survival (OS) was examined via Kaplan-Meier analysis to assess their prognostic significance. A prognostic model based on seven CDK genes was constructed using Lasso and Cox regression, and the predictive performance of the model was analyzed using Kaplan-Meier analysis and column line plots. The correlation between CDK genes and immune cells was also examined. Patients with EC in the high-risk group had a poorer prognosis. The results of qRT-PCR and immunohistochemical analyses validated that CDK16 is highly expressed in EC tissues. Patients with EC with high CDK16 expression had worse 10-year OS than patients with low CDK16 expression. These findings suggest that the prognostic model constructed based on CDK genes can help to develop individualized and targeted treatment strategies for patients with EC.
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Introduction: A number of evidences have proved that "Nostoc commune" Vauch can improve human immunity and prevent diseases, however, the specific mechanism remains unclear. The biological activity of the main protein component of "Nostoc commune" Vauch extracellular matrix- a water-stress protein (WSP) still needs to be elucidated. Methods: In our study, we validated the role of WSP in gastric cancer metastasis at the cellular level, the organoid level and in mouse models, and also studied the role of EGFRVIII and downstream signaling molecules after WSP treatment. Results: We found that WSP can significantly inhibit the metastasis of gastric cancer cells. Interestingly, we found that the anti-metastasis ability of WSP on gastric cancer was related to membrane protein receptor EGFRVIII, which was realized by inhibiting the downstream EGFRVIII signaling pathway. In terms of mechanism, WSP can inhibit the downstream EGFRVIII signaling pathway Akt-PI3K and further inhibit the secretion of cancer-related metastasis proteins such as MMP2 and MMP9, thus, significantly affecting the metastasis of gastric cancer cells. Discussion: Given the anticancer properties of WSP, drug developers and manufacturers can further develop protein drugs for cancer patients using protein engineering techniques based on the properties of WSP.
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OBJECTIVE: Lynch syndrome (LS) pre-screening methods remain under-investigated in colorectal cancers (CRCs) in Asia. Here, we aimed to systematically investigate LS pre-screening and comprehensively characterize LS CRCs. METHODS: Microsatellite instability (MSI) and germline variants of DNA mismatch repair (MMR) genes were examined in 406 deficient MMR (dMMR) and 250 proficient MMR CRCs. The genetic differences between LS and sporadic CRCs were studied with whole exome sequencing analysis. RESULTS: The incidence of dMMR in Chinese patients with CRCs was 13.8%. Consistency analysis between MMR immunohistochemistry (IHC) and MSI testing showed the kappa value was 0.758. With next-generation sequencing (NGS), germline variants were detected in 154 CRCs. Finally, 88 patients with CRC were identified as having LS by Sanger sequencing. Among them, we discovered 21 previously unreported pathogenic germline variants of MMR genes. Chinese patients with LS, compared with sporadic CRCs, tended to be early-onset, right-sided, early-stage and mucinous. Overall, the performance of MMR IHC and MSI testing for LS pre-screening was comparable: the area under the ROC curve for dMMR, MSI-H, and MSI-H/L was 0.725, 0.750, and 0.745, respectively. dMMR_MSI-H LS and sporadic CRCs showed substantial differences in somatic genetic characteristics, including different variant frequencies of APC, CREBBP, and KRAS, as well as different enriched pathways of VEGF, Notch, TGFßR, mTOR, ErbB, and Rac protein signal transduction. CONCLUSIONS: MMR IHC and MSI testing were effective methods for LS pre-screening. The revealed clinical and somatic genetic characteristics in LS CRCs may have the potential to improve the performance of LS pre-screening in combination with dMMR/MSI.
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Neoplasias Colorrectales Hereditarias sin Poliposis , Humanos , China/epidemiología , Neoplasias Colorrectales Hereditarias sin Poliposis/diagnóstico , Neoplasias Colorrectales Hereditarias sin Poliposis/genética , Neoplasias Colorrectales Hereditarias sin Poliposis/patología , Detección Precoz del Cáncer/métodos , Inestabilidad de Microsatélites , Proteínas Proto-Oncogénicas p21(ras)/genética , Serina-Treonina Quinasas TOR/genética , Serina-Treonina Quinasas TOR/metabolismo , Factor A de Crecimiento Endotelial Vascular/metabolismoRESUMEN
OBJECTIVE: Low serum adiponectin level can predict hypertension development, and adiponectin gene (ADIPOQ) polymorphisms have been reported to be linked with hypertension risk. Whereas, the interaction between ADIPOQ polymorphisms and environmental factors on the susceptibility of hypertension remained unclear. The purpose of this study was to explore the relationship of ADIPOQ polymorphisms with hypertension risk and their interaction with lipid levels in coal miners. METHODS: A matched case-control study with 296 case-control pairs was performed in a large coal mining group located in North China. The participants were questioned by trained interviewers, and their ADIPOQ genotype and lipid levels were determined. Logistic regression, stratified analysis, and crossover analysis were applied to evaluate the effects of rs2241766, rs1501299, and rs266729 genotypes and gene-lipid interaction on hypertension risk. RESULTS: In this matched case-control study, the genotypes of rs2241766 TG+GG, rs1501299 GT+TT, and rs266729 CG+GG were marginally related to hypertension risk. Individuals with high total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) level were susceptible to hypertension (TC: odds ratio [OR] = 1.807, 95% confidence intervals [95%CI] = 1.266-2.581; LDL-C: OR = 1.981, 95%CI = 1.400-2.803; HDL-C: OR = 1.559, 95%CI = 1.093-2.223). Antagonistic interactions were detected between rs2241766 and TC, rs1501299 and TC, rs2241766 and LDL-C, and rs1501299 and HDL-C (rs2241766 and TC: OR = 0.393, 95%CI = 0.191-0.806; rs1501299 and TC: OR = 0.445, 95%CI = 0.216-0.918; rs2241766 and LDL-C: OR = 0.440, 95%CI = 0.221-0.877; rs1501299 and HDL-C: OR = 0.479, 95%CI = 0.237-0.967). Stratified analysis showed that hypertension risk was high for the subjects with rs2241766 TG+GG or rs1501299 GG under the low lipid level but low for those under the high lipid level. In the case group, the TC and LDL-C levels for rs2241766 TG+GG were lower than those for rs2241766 GG, and the TC and HDL-C levels for rs1501299 GT+TT were higher than those for rs1501299 GG. CONCLUSIONS: Although the effects of ADIPOQ polymorphisms alone were not remarkable, an antagonistic interaction was observed between ADIPOQ polymorphisms and lipid levels.