Regulation of the PD-1/PD-L1 Axis and NK Cell Dysfunction by Exosomal miR-552-5p in Gastric Cancer.

OBJECTIVE: NK cells play a vital role in tumor immune resistance. Various factors affect NK cell activity. While NK cell dysfunction has been observed in numerous malignancies, the underlying mechanisms in gastric cancer remain unclear. METHOD: Flow cytometry was used to identify the phenotypic distribution and expression of activated receptors on NK cells. ELISA was used to determine the expression of cytokines. We examined the expression of NK cell-related genes and explored their association with survival and prognosis. Additionally, we conducted PCR detection of miR-552-5p expression levels in plasma exosomes of patients and investigated its correlation with phenotypic distribution and activated receptors. We used flow cytometry and ELISA to verify the role of miR-552-5p in NK cell dysfunction. Furthermore, we investigated the potential role of PD-1/PD-L1 in regulating NK cell dysfunction in patients' cells. RESULTS: We observed a significant decrease in the percentage of NKG2D and NKp30 and IFN-γ and TNF-α in patients than in healthy volunteers. Patients with low levels of CD56, CD16, NKG2D, and NKP46 exhibited poorer survival prognoses. Moreover, increased expression levels of plasma exosomal miR-552-5p in patients were negatively associated with NK cell phenotypic distribution and activated receptor expression. MiR-552-5p downregulated the secretion of perforin, granzyme, and IFN-γ as well as the expression of NKp30, NKp46, and NKG2D. Additionally, it suppressed the cytotoxicity of NK cells. The inhibitory effect of miR-552-5p, on NK cell function was reversed when anti-PD-L1 antibodies were used. CONCLUSION: Exosomal miR-552-5p targets the PD-1/PD-L1 axis, leading to impaired NK cell function.

Tumor cell SPTBN1 inhibits M2 polarization of macrophages by suppressing CXCL1 expression.

Tumor-associated macrophages (TAMs) are the most abundant immune cells in the tumor microenvironment, and the M2-type TAMs can promote tumor growth, invasion and angiogenesis, and suppress antitumor immune responses. It has been reported that spectrin beta, non-erythrocytic 1 (SPTBN1) may inhibit the infiltration of macrophages in Sptbn1+/-  mouse liver, but whether tumor SPTBN1 affects TAMs polarization remains unclear. This study investigated the effect and mechanism of tumor cell SPTBN1 on polarization and migration of TAMs in hepatoma and breast cancer. By analyzing tumor immune databases, we found a negative correlation between SPTBN1 and abundance of macrophages and myeloid-derived suppressor cells (MDSCs) in the tumor microenvironment. By reverse transcription-quantitative real-time PCR assays and cell migration assays, the migration and M2 polarization of macrophages were enhanced by the culture medium from hepatocellular carcinoma cell line PLC/PRF/5, SNU449, and breast cancer cell line MDA-MB-231 with SPTBN1 suppression, which could be reversed by CXCL1 neutralizing antibody MAB275. Meanwhile, the ability of migration and colony formation of PLC/PRF/5, SNU449, and MDA-MB-231 cells were promoted when coculture with M2 macrophages. We also found that SPTBN1 regulated CXCL1 through p65 by cytoplasmic-nuclear protein isolation experiments and ChIP-qPCR. Our data suggest that tumor cell SPTBN1 inhibits migration and M2-type polarization of TAMs by reducing the expression and secretion of CXCL1 via inhibiting p65 nuclear localization.

Identifying pathogenicity-related genes in the pathogen Colletotrichum magnum causing watermelon anthracnose disease via T-DNA insertion mutagenesis.

Fruit rot caused by Colletotrichum magnum is a crucial watermelon disease threatening the production and quality. To understand the pathogenic mechanism of C. magnum, we optimized the Agrobacterium tumefaciens-mediated transformation system (ATMT) for genetic transformation of C. magnum. The transformation efficiency of ATMT was an average of around 245 transformants per 100 million conidia. Southern blot analysis indicated that approximately 75% of the mutants contained a single copy of T-DNA. Pathogenicity test revealed that three mutants completely lost pathogenicity. The T-DNA integration sites (TISs) of three mutants were Identified. In mutant Cm699, the TISs were found in the intron region of the gene, which encoded a protein containing AP-2 complex subunit σ, and simultaneous gene deletions were observed. Two deleted genes encoded the transcription initiation protein SPT3 and a hypothetical protein, respectively. In mutant Cm854, the TISs were found in the 5'-flanking regions of a gene that was similar to the MYO5 encoding Myosin I of Pyricularia oryzae (78%). In mutant Cm1078, the T-DNA was integrated into the exon regions of two adjacent genes. One was 5'-3' exoribonuclease 1 encoding gene while the other encoded a WD-repeat protein retinoblastoma binding protein 4, the homolog of the MSl1 of Saccharomyces cerevisiae.

FoxO and rotund form a binding complex governing wing polyphenism in planthoppers.

Wing polyphenism is found in a variety of insects and offers an attractive model system for studying the evolutionary significance of dispersal. The Forkhead box O (FoxO) transcription factor (TF) acts as a wing-morph switch that directs wing buds developing into long-winged (LW) or short-winged morphs in wing-dimorphic planthoppers, yet the regulatory mechanism of the FoxO module remains elusive. Here, we identified the zinc finger TF rotund as a potential wing-morph regulator via transcriptomic analysis and phenotypic screening in the brown plathopper, Nilaparvata lugens. RNA interference-mediated knockdown of rotund antagonized the LW development derived from in the context of FoxO depletion or the activation of the insulin/insulin-like growth factor signaling cascade, reversing long wings into intermediate wings. In vitro binding assays indicated that rotund physically binds to FoxO to form the FoxO combinatorial code. These findings broaden our understanding of the complexity of transcriptional regulation governing wing polyphenism in insects.

Robust reconstruction of fluorescence molecular tomography based on adaptive adversarial learning strategy.

Objective.Fluorescence molecular tomography (FMT) is a promising molecular imaging modality for quantifying the three-dimensional (3D) distribution of tumor probes in small animals. However, traditional deep learning reconstruction methods that aim to minimize the mean squared error (MSE) and iterative regularization algorithms that rely on optimal parameters are typically influenced by strong noise, resulting in poor FMT reconstruction robustness.Approach.In this letter, we propose an adaptive adversarial learning strategy (3D-UR-WGAN) to achieve robust FMT reconstructions. Unlike the pixel-based MSE criterion in traditional CNNs or the regularization strategy in iterative solving schemes, the reconstruction strategy can greatly facilitate the performance of the network models through alternating loop training of the generator and the discriminator. Second, the reconstruction strategy combines the adversarial loss in GANs with the L1 loss to significantly enhance the robustness and preserve image details and textual information.Main results.Both numerical simulations and physical phantom experiments demonstrate that the 3D-UR-WGAN method can adaptively eliminate the effects of different noise levels on the reconstruction results, resulting in robust reconstructed images with reduced artifacts and enhanced image contrast. Compared with the state-of-the-art methods, the proposed method achieves better reconstruction performance in terms of target shape recovery and localization accuracy.Significance.This adaptive adversarial learning reconstruction strategy can provide a possible paradigm for robust reconstruction in complex environments, and also has great potential to provide an alternative solution for solving the problem of poor robustness encountered in other optical imaging modalities such as diffuse optical tomography, bioluminescence imaging, and Cherenkov luminescence imaging.

Ethylene enhances resistance to cucumber green mottle mosaic virus via the ClWRKY70-ClACO5 module in watermelon plants.

Introduction: Ethylene (ET) is involved in plant responses to viral infection. However, its molecular mechanisms and regulatory network remain largely unknown. Methods and results: In the present study, we report that cucumber green mottle mosaic virus (CGMMV) in watermelon (Citrullus lanatus) triggers ET production by inducing the expression of ClACO5, a key gene of the ET biosynthesis pathway through transcriptome data analysis and gene function validation. The knock-down of ClACO5 expression through virus-induced gene silencing in watermelon and overexpressing ClACO5 in transgenic Nicotiana benthamiana indicated that ClACO5 positively regulates CGMMV resistance and ET biosynthesis. The salicylic acid-responsive transcription factor gene ClWRKY70 shares a similar expression pattern with ClACO5. We demonstrate that ClWRKY70 directly binds to the W-box cis-element in the ClACO5 promoter and enhances its transcription. In addition, ClWRKY70 enhances plant responses to CGMMV infection by regulating ClACO5 expression in watermelon. Discussion: Our results demonstrate that the ClWRKY70-ClACO5 module positively regulates resistance to CGMMV infection in watermelon, shedding new light on the molecular basis of ET accumulation in watermelon in response to CGMMV infection.

AC5 protein encoded by squash leaf curl China virus is an RNA silencing suppressor and a virulence determinant.

Squash leaf curl China virus (SLCCNV) is a bipartite Begomovirus. The function of the protein AC5, which is encoded by SLCCNV, is unknown. Here, we confirmed that the 172-amino acids (aa) long AC5 protein of SLCCNV could suppress single-stranded RNA but not double-stranded RNA-induced post-transcriptional gene silencing (PTGS). Furthermore, we determined that the C-terminal domain (96-172 aa) of the AC5 protein was responsible for RNA silencing suppressor (RSS) activity via deletion mutant analysis. The AC5 protein can reverse GFP silencing and inhibit systemic silencing of GFP by interfering with the systemic spread of the GFP silencing signal. The SLCCNV AC5 protein was localized to both the nucleus and cytoplasm of Nicotiana benthamiana cells. Furthermore, deletion analysis showed that the putative nuclear localization signal (NLS, 102-155 aa) was crucial for the RNA silencing suppression activity of AC5. In addition, the AC5 protein elicited a hypersensitive response and enhanced potoao virus X (PVX) RNA accumulation in infected N. benthamiana plants. Using the infectious clones of the SLCCNV and SLCCNV-AC5 null mutants, mutational analysis confirmed that knockout of the AC5 gene abolished SLCCNV-induced leaf curl symptoms, showing SLCCNV AC5 is also a virulence determinant.

Clinical efficacy of early postoperative intensity-modulated radiotherapy combined with Temozolomide chemotherapy in the treatment of patients with malignant glioma.

Objectives: To evaluate the clinical efficacy of early postoperative intensity-modulated radiotherapy (IMRT) combined with temozolomide chemotherapy in the treatment of patients with malignant glioma. Methods: In this retrospective cohort study 80 patients with glioma surgery admitted to Chengde Central Hospital from January 2019 to January 2021 were selected and divided into two groups according to postoperative treatment: the experimental group and the control group, with 40 cases in each group. Patients in the experimental group received IMRT combined with temozolomide chemotherapy postoperatively, while those in the control group received IMRT alone. The clinical effects of patients were analyzed before treatment and three months after treatment, and the incidence of adverse reactions such as bone marrow suppression, gastrointestinal reactions, fever, and liver dysfunction were analyzed in the two groups within one month after treatment. Before treatment and two months after treatment, MMSE scale, QOL scale and KPS were used to compare the cognitive function and health status of the patients. All patients were followed up for one year after treatment, and the difference of disease progression-free survival and overall survival rate between the two groups was analyzed. Results: The effective rate of the experimental group was 70% after treatment, while that of the control group was 43.3%, with a statistically significant difference (P=0.04). The incidence of adverse reactions was 50% in the experimental group and 40% in the control group, with no statistically significant difference between the two groups (P=0.25). After treatment, MMSE score, QOL score and KPS score of the experimental group were significantly improved compared with those of the control group, with statistically significant differences between the two groups (MMSE score, QOL, P=0.00; KPS, P=0.01). Moreover, the two groups of patients were followed up for one year after treatment. The disease progression-free survival rate of the experimental group was 70% and that of the control group was 47.5%, with a statistically significant difference (P=0.04), and the overall survival rate of the experimental group was significantly higher than that of the control group after treatment, with a statistically significant difference (P=0.03). Conclusion: Early postoperative IMRT combined with temozolomide chemotherapy is an effective treatment regimen for patients with malignant glioma, boasting a variety of advantages such as high efficiency, cognitive function, favorable recovery of health status, significantly improved progression-free survival rate and overall survival rate, and no significant increase in adverse reactions.

Association between interleukin-19 gene polymorphisms and maternal puerperal infection.

Any bacterial infection of the genital tract after childbirth is called maternal puerperal infection. This infection accounts for 13% of pregnancy-related deaths and is the fifth leading cause of maternal mortality. Endometritis (postpartum uterine infection) has been associated with preeclampsia and maternal lethal bleeding in recent decades. In some studies, the presence of meconium in the amniotic fluid has been implicated in the development of endometritis. The study aimed to evaluate the association between interleukin-19 gene polymorphisms and maternal puerperal infection. In this study, 300 pregnant women with a gestational age of at least 37 weeks were studied. Patients were divided into two groups of 150 controls and cases. In the case group, amniotic fluid was impregnated with meconium, and in the control group, it was clear fluid. Both groups underwent cesarean section, and all received prophylactic antibiotics before surgery. Patients were evaluated for purpura infection in the first 40 days after delivery. Five ml of venous blood was taken from each patient and transferred to a tube containing EDTA anticoagulant. Genomic DNA was isolated using a particular kit. Then, the polymerase chain reaction was performed by the ARMS method. Data were analyzed using the chi-square test and SPSS software version 19 in case and control groups. This study's results indicate no significant difference in the frequency of AG, GG, and AA genotypes at position rs2243191 and rs1028181 IL-19 gene polymorphism between patients with puerperal infection and the control group (P>0.05). Also, no significant difference was observed in the frequency of both G and A alleles in the mentioned situations between patients and the control group (P>0.05). Based on the results of this study, no significant relationship was observed between IL-19 gene polymorphism at rs2243191 and rs1028181 locus and puerperal infection.

Exosomal miR-552-5p promotes tumorigenesis and disease progression via the PTEN/TOB1 axis in gastric cancer.

Purpose Gastric cancer (GC) is associated with rapid disease progression and poor patient prognosis, highlighting the pressing need for new biomarkers to facilitate disease management. Exosomes are released by all cells and are ubiquitous in body fluids, thus giving them great potential as diagnostic biomarkers and therapeutic targets. MicroRNAs (miRNAs) can be transported by exosomes, and are a common target for regulation in cancer. Methods Our screen of miRNAs in the Gene Expression Omnibus and The Cancer Genome Atlas databases identified miR-552-5p as the most overexpressed miRNA in GC, and we investigated its function and mechanism of action. Results We detected high expression of miR-552-5p in GC tissues, plasma samples and cell lines. We found that miR-552-5p binds directly to the 3'-untranslated region of PTEN, and the resulting downregulation of PTEN in turn downregulates the tumor suppressor TOB1. Furthermore, experiments in cell culture and mice showed that miR-552-5p in exosomes is internalized by recipient cells, where it enhances proliferation, migration and the epithelial-mesenchymal transition, while suppressing the caspase-3 apoptotic pathway. These effects were reversed by inhibiting miR-552-5p. Conclusion GC-derived exosomal miR-552-5p facilitates tumorigenesis by interfering with the PTEN/TOB1 axis, providing new potential therapeutic targets.

Loss of SPTBN1 Suppresses Autophagy Via SETD7-mediated YAP Methylation in Hepatocellular Carcinoma Initiation and Development.

BACKGROUND & AIMS: Loss of Spectrin beta, non-erythrocytic 1 (SPTBN1) plays an important role in the carcinogenesis of hepatocellular carcinoma (HCC); however, the mechanisms underlying its involvement remain poorly understood. Defects in autophagy contribute to hepatic tumor formation. Hence, in this study, we explored the role and mechanism of SPTBN1 in the autophagy of hepatic stem cells (HSCs) and HCC cells. METHODS: Expansion, autophagy, and malignant transformation of HSCs were detected in the injured liver of Sptbn1+/- mice induced by 3,5-diethoxycarbonyl-1,4-dihydrocollidine treatment. Hippo pathway and Yes-associated protein (YAP) stabilization were examined in isolated HSCs, Huh-7, and PLC/PRF/5 HCC cells and hepatocytes with or without loss of SPTBN1. RESULTS: We found that heterozygous SPTBN1 knockout accelerated liver tumor development with 3,5-diethoxycarbonyl-1,4-dihydrocollidine induction. Rapamycin promoted autophagy in murine HSCs and reversed the increased malignant transformation induced by heterozygous SPTBN1 deletion. Loss of SPTBN1 also decreased autophagy and increased YAP stability and nuclear localization in human HCC cells and tissues, whereas YAP inhibition attenuated the effects of SPTBN1 deficiency on autophagy. Finally, we found that SPTBN1 positively regulated the expression of suppressor of variegation 3-9-enhancer of zeste-trithorax domain containing lysine methyltransferase 7 to promote YAP methylation, which may lead to YAP degradation and inactivation. CONCLUSIONS: Our findings provide the first demonstration that loss of SPTBN1 impairs autophagy of HSCs to promote expansion and malignant transformation during hepatocarcinogenesis. SPTBN1 also cooperates with suppressor of variegation 3-9-enhancer of zeste-trithorax domain containing lysine methyltransferase 7 to inactive YAP, resulting in enhanced autophagy of HCC cells. These results may open new avenues targeting SPTBN1 for the prevention and treatment of HCC.

Survival-Related lncRNA Landscape Analysis Identifies LINC01614 as an Oncogenic lncRNA in Gastric Cancer.

Background: Long non-coding RNAs (lncRNAs) reportedly play important roles in biomarker and tumorigenesis of gastric cancer (GC). This study aimed to determine the potential application of prognostic lncRNA signature and identified the role of LINC01614 in carcinogenesis in GC. Material and Methods: Data accessed from the Cancer Genome Atlas database was used to construct a lncRNA signature. Joint effect analysis of the signature and clinical parameters was performed to verify the clinical value of the signature. Co-expression analysis was conducted for prognostic lncRNAs and protein-coding genes. Moreover, the relative expression of LINC01614 was validated in GC tissues and cell lines. In vitro and in vivo experiments were conducted to analyze the biological functions of the newly identified gene in GC cells. Results: A seven-lncRNA (LINC01614, LINC01537, LINC01210, OVAAL, LINC01446, CYMP-AS1, and SCAT8) signature was identified as a promising prognostic signature in GC. Results indicated that the seven-lncRNA was involved in tumorigenesis and progression pathways. LINC01614 expression was identified and found to be upregulated in GC tissues and cells. The study findings revealed that LINC01614 promoted cell proliferation, migration, invasion, and epithelial-mesenchymal transition. Knockdown of LINC01614 arrested cell cycle distribution at the G2/M phase. Further, LINC01614 also promoted tumor growth in vivo. Conclusion: We developed an independent seven-lncRNA biomarker for prognostic prediction and identified LINC01614 as an oncogenic lncRNA in GC.

Development and identification of a prognostic nomogram model for patients with mixed cell adenocarcinoma of the ovary.

BACKGROUND: Mixed cell ovarian adenocarcinoma (MCOA) is a malignant gynecologic tumor consisting of serous, mucous, and papillary tumor cells. However, the clinical features and prognosis of MCOA patients are unclear. METHODS: In this study, univariate and multivariate Cox proportional risk models were performed to identify independent prognostic factors. The Kaplan-Meier method was used to assess the relationship between clinical characteristics and patient survival. Finally, a nomogram was constructed and validated to predict patient survival time, and the C-index was used to evaluate the efficacy of the nomogram. RESULTS: A total of 2,818 patients diagnosed with MCOA were identified, and the 5-year survival rate was 62%. Univariate and multivariate Cox models suggested that age (HR=1.28, 95% CI[1.15,1.44]), grade (HR=1.26, 95% CI[1.12,1.41]), SEER stage (HR=1.63, 95% CI[1.25,2.13]) and AJCC (American Joint Committee on Cancer) stage (HR=1.59, 95% CI[1.36,1.86]) were independent prognostic factors for MCOA patients. After propensity score matching for age, grade, SEER stage, and AJCC stage, the 5-year survival rate was 69.7% for ovarian serous cystadenocarcinoma and 62.9% for ovarian papillary serous cystadenocarcinoma. These results mean that serous adenocarcinoma had the best prognosis of the three pathologic types of ovarian carcinoma (p<0.0001), with no significant difference between papillary serous cystadenocarcinoma and MCOA (p=0.712). Finally, a nomogram consisting of age, grade, SEER stage, and AJCC stage was established and validated to predict the survival time, with C-indices of 0.743 and 0.731, respectively. CONCLUSIONS: In summary, MCOA is uncommon, and age, grade, SEER stage, and AJCC stage are independent prognostic factors. Compared with other common malignant ovarian tumors, MCOA has a poor prognosis.

MiR-199b-5p Promotes Gastric Cancer Progression by Regulating HHIP Expression.

OBJECTIVES: Gastric cancer (GC) is one of the most common malignant tumors. More and more evidences support the role of microRNAs (miRNAs) in tumor progression. However, the role of miRNAs in human GC remains largely unknown. METHODS: Based on the published gastric cancer expression profile data, combined with bioinformatics analysis, potential miRNAs in the process of GC were screened. The expression of miR-199b-5p in GC cells and patients' plasma was detected by RT-PCR. The effects of miR-199b-5p on GC in vitro were detected by EdU proliferation assay, colony formation assay, Transwell assay and wound healing assay. Western blot was used to detect epithelial-mesenchymal transition (EMT) related proteins. The subcutaneous tumorigenesis model and metastatic tumor model of mice were used to study its effect in vivo. Bioinformatics and Dual luciferase reporter assay were used to verify the effect of miR-199b-5p and its target gene. RESULTS: Through bioinformatics analysis, we screened a novel miRNA miR-199b-5p that was significantly up-regulated in GC tissue and associated with poor prognosis of GC patients. RT-PCR results showed that its expression was also up-regulated in GC cell lines and patients' plasma. MiR-199b-5p can significantly promote GC cell proliferation and migration in vitro and in vivo. Western blot showed that miR-199b-5p could promote the EMT process of GC. HHIP has been proved to be a target of miR-199b-5p, and the recovery of HHIP can weaken the effect of miR-199b-5p. CONCLUSION: MiR-199b-5p may play an oncogene role in GC by targeting HHIP, suggesting that miR-199b-5p may be a potential therapeutic target for GC.

SPTBN1 inhibits growth and epithelial-mesenchymal transition in breast cancer by downregulating miR-21.

SPTBN1 (spectrin beta, non-erythrocytic 1) has been linked to tumor progression and epithelial-mesenchymal transition (EMT). However, the role of SPTBN1 has yet to be investigated in breast cancer. This study aimed to evaluate the viability, growth, and migration ability of the breast cancer cell line MDA-MB-231 and BT549 using CCK-8 assay, xenograft models, and Transwell assays. The expression of SPTBN1, EMT-related genes, and miRNA21 in breast cancer cells and tissues were assessed by quantitative real-time polymerase chain reaction (qPCR) and Western blot. SPTBN1 staining of breast cancer tissues was analyzed by the Human Protein Atlas databases. Both chromatin immunoprecipitation qPCR and immunofluorescence were performed to detect how SPTBN1 regulates miRNA21. Our results showed that the expression of SPTBN1 in primary breast cancer tumors was dramatically lower than that in normal tissues and that lower levels of SPTBN1 were associated with significantly shorter progression-free survival. We also discovered that the loss of SPTBN1 promotes EMT, the viability of MDA-MB-231 and BT549 in vitro, and the growth of MDA-MB-231 tumor xenografts in vivo by upregulating miR-21 level. Furthermore, loss of SPTBN1-mediated miR-21 upregulation was dependent on the stability and nuclear translocation of NF-κB p65. Therefore, SPTBN1 is a pivotal regulator that inhibits EMT and the growth of breast cancer.

CircRNA-Mediated Regulation of Angiogenesis: A New Chapter in Cancer Biology.

Angiogenesis is necessary for carcinoma progression and is regulated by a variety of pro- and anti-angiogenesis factors. CircRNAs are RNA molecules that do not have a 5'-cap or a 3'-polyA tail and are involved in a variety of biological functions. While circRNA-mediated regulation of tumor angiogenesis has received much attention, the detailed biological regulatory mechanism remains unclear. In this review, we investigated circRNAs in tumor angiogenesis from multiple perspectives, including its upstream and downstream factors. We believe that circRNAs have natural advantages and great potential for the diagnosis and treatment of tumors, which deserves further exploration.

The Outcome of Primary Hepatic Carcinoid Tumor: A Retrospective Study Based on Propensity Score Matched Survival Analysis.

BACKGROUND: Primary hepatic carcinoid tumor (PHCT) is rare and has unclear clinical characteristics and prognosis. METHODS: A retrospective study using data from the SEER database for patients diagnosed with PHCT used univariate and multivariate Cox models to screen for independent prognostic factors. The outcomes of patients in the surgical and nonsurgical groups were compared, and Propensity Score Matching (PSM) analysis was used to reduce confounder bias. RESULTS: A total of 186 PHCT patients were identified and the median survival was 65 (95% CI [43.287, 86.713]) months. Tumor size(HR = 2.493, 95% CI[1.222,5.083], p = 0.012), male(HR = 1.690, 95% CI[1.144,2.497], p = 0.008), age(HR = 2.583, 95% CI[1.697,3.930], p < 0.001), SEER stage(HR = 1.555, 95% CI[1.184,2.044], p = 0.002) and surgery(HR = 0.292, 95% CI[0.135,0.634], p = 0.002) were significantly correlated with patient prognosis. In multivariate analysis, sex(HR = 3.206, 95% CI[1.311,7.834], p = 0.011) and surgery(HR = 0.204, 95% CI[0.043,0.966], p = 0.0045) were independent predictors of patient prognosis. Females are potentially susceptible to PHCT but have a better prognosis. With consistent baseline data, surgical patients have a better prognosis. CONCLUSIONS: PHCT is uncommon and survival time is longer than that of other primary liver cancers. We found that none-surgery was potentially independent risk factors for poor prognosis.

Surgery and chemotherapy improve the prognosis of primary hepatic angiosarcoma: A retrospective study based on Propensity score matched survival analysis.

PURPOSE: Hepatic angiosarcoma(HAS) is rare and is the primary vascular-derived malignancy of the liver. Its clinical characteristics, therapeutic strategy management, and the outcome are unclear. METHODS: This is a retrospective study of patients from the SEER database. Survival analysis was performed by the Kaplan-Meier method. Univariate and multivariate Cox models were used to identify risk factors. Propensity Score Matching(PSM) analysis was used to remove confounding bias. The nomogram was constructed, and the performance was measured using the C-index. RESULTS: A total of 300 HAS patients diagnosed between 1975 and 2016 were identified for this study, with an estimated median cancer-specific survival(CSS) of 1 month. The median CSS was 6 months in both the surgery and chemotherapy groups. Age(HR = 1.5206, p = 0.0058), sex(HR = 1.3906, p = 0.0391), SEER stage(HR = 1.4426, p < 0.0001), surgery(HR = 0.4493, p = 0.0001) and chemotherapy(HR = 0.28161, p < 0.0001) are potential independent prognostic factors. Of these HAS patients, 29 received surgical treatment without chemotherapy, and 63 received chemotherapy without surgery. A 1:1 PSM was performed to select candidates from the surgery-only group and the chemotherapy-only group. The survival analysis showed that the median survival time was 3 months in the surgery-only cohort and 5 months in the chemotherapy-only cohort, and there was no statistical difference between the two groups. Finally, a nomogram was constructed, with a C-index of 0.754. CONCLUSIONS: HAS is uncommon and has a poor prognosis. It was found that age, sex, SEER stage, surgery, and chemotherapy were independent prognostic factors for patients. Both surgery and chemotherapy could significantly prolong the survival of patients, and there was no statistical difference between the prognosis of patients treated with chemotherapy alone and those treated with surgery alone.

Comparison of the diagnostic efficacy of blue laser imaging with narrow band imaging for gastric cancer and precancerous lesions: a meta-analysis.

BACKGROUND AND AIMS: novel endoscopic techniques including narrowband imaging (NBI) and blue laser imaging (BLI) have led to the improved detection of early stage gastric cancer and precancerous lesions. However, these techniques are not generally thought to be equivalent at present and BLI is generally considered as superior to NBI. Therefore, this comprehensive meta-analysis aimed to definitively compare the diagnostic efficacy of NBI and BLI for the diagnosis of gastric cancer and precancerous lesions. METHODS: relevant articles were identified via searches of the PubMed, Web of Science, Embase and Cochrane Library databases from their inception until October 2019. In total, 28 relevant studies were identified and incorporated into the meta-analysis. RevMan5.3 was used to assess the relative diagnostic efficacy of these two imaging modalities in these studies. The threshold was assessed using Meta-DiSc 1.4 and STATA 14.0 for bivariate regression modeling of pooled studies. RESULTS: the pooled sensitivity of BLI for gastric cancer was 0.89 (0.80, 0.95) and the specificity was 0.92 (0.76, 0.98). The pooled sensitivity of NBI for gastric cancer was 0.83 (0.75, 0.89) and the specificity was 0.95 (0.91, 0.97). The pooled sensitivity of BLI for precancerous lesions was 0.81 (0.71, 0.87) and the specificity was 0.90 (0.80, 0.96). The pooled sensitivity of NBI for precancerous lesions was 0.80 (0.75, 0.85) and the specificity was 0.88 (0.77, 0.94). CONCLUSIONS: this study showed that both BLI and NBI have a very high diagnostic efficacy for the detection of gastric cancer and precancerous lesions, the sensitivity and specificity of these two approaches were similar.

SPTBN1 suppresses the progression of epithelial ovarian cancer via SOCS3-mediated blockade of the JAK/STAT3 signaling pathway.

SPTBN1 plays an anticancer role in many kinds of tumors and participates in the chemotherapeutic resistance of epithelial ovarian cancer (EOC). Here, we reported that lower SPTBN1 expression was significantly related to advanced EOC stage and shorter progression-free survival. SPTBN1 expression was also higher in less invasive EOC cell lines. Moreover, SPTBN1 decreased the migration ability of the EOC cells A2780 and HO8910 and inhibited the growth of EOC cells in vitro and tumor xenografts in vivo. SPTBN1 suppression increased the epithelial mesenchymal transformation marker Vimentin while decreasing E-cadherin expression. By analyzing TCGA data and immunohistochemistry staining of tumor tissue, we found that SPTBN1 and SOCS3 were positively coexpressed in EOC patients. SOCS3 overexpression or JAK2 inhibition decreased the proliferation and migration of EOC cells as well as the expression of p-JAK2, p-STAT3 and Vimentin, which were enhanced by the downregulation of SPTBN1, while E-cadherin expression was also reversed. It was also verified in mouse embryonic fibroblasts (MEFs) that loss of SPTBN1 activated the JAK/STAT3 signaling pathway with suppression of SOCS3. Our results suggest that SPTBN1 suppresses the progression of epithelial ovarian cancer via SOCS3-mediated blockade of the JAK/STAT3 signaling pathway.