Effectiveness and Safety of Different Patch Materials for Supravalvar Aortic Stenosis (Middle-Term Outcomes).

Background: To determine the effectiveness and safety of different patch materials in the treatment of pediatric patients with congenital supravalvular aortic stenosis (SVAS). Methods: 218 consecutive SVAS patients (age < 14 years) who underwent surgery from Beijing Fuwai and Yunnan Fuwai hospital between 2002 and 2020 were included. Patients were divided into the pericardium patch group (133 (61.0%)), modified patch group (43 (19.7%)) and artificial patch group (42 (19.3%)). The primary safety endpoint was patch-related adverse complications (post-operation patch hemorrhage or aortic sinus aneurysm at 2-year follow-up). The primary effectiveness outcome was the re-operation or restenosis at 2-year follow-up. Multivariable cox regression was used to obtain the hazard ratio (HR). Results: The median age at operation was 43.5 months (IQR 24.0-73.0). Only three patients had patch-related adverse complications, and no difference existed among the three groups (p = 0.763). After a median follow-up of 24.0 months (IQR 6.0-48.0), patients with a pericardium patch had a lower re-operation or restenosis rate compared with the other two groups (pericardium patch vs modified patch, HR = 0.30, 95% CI 0.12-0.77; pericardium patch vs artificial patch, HR = 0.33, 95% CI 0.13-0.82), even in the main subgroup and sensitivity analysis. Conclusions: In pediatric patients, the safety of autologous pericardium patch is acceptable, along with lower rates of middle-term re-operation or restenosis. Clinical Trial Registration: http://www.chictr.org.cn, number: ChiCTR2300067851.

Impact of pulmonary artery intramural hematoma on patients with acute type A aortic dissection.

OBJECTIVES: To investigate the short-term/long-term impact of pulmonary artery intramural hematoma (PA-IMH) in patients with acute Stanford type A aortic dissection (ATAAD) following surgical repair. MATERIALS AND METHODS: Consecutive patients with ATAAD who received surgical repair at Beijing and Yunnan Fuwai Hospital in 2010-2021 were retrospectively reviewed. Patients with hemorrhage extending along the PA were identified as the PA-IMH group. Multivariable logistics regression was used to obtain the odds ratio (OR), and the Kaplan-Meier method was used to estimate the survival rate. RESULTS: Of the 2046 ATAAD patients, 324 (15.8%) patients were identified with PA-IMH, and 1722 (84.2%) were without PA-IMH. PA-IMH had a higher prevalence in patients with older age, female gender, aortic IMH, and type II aortic dissection. PA-IMH patients incurred excess early mortality compared with non-PA-IMH patients (9.3% vs. 5.6%, OR = 1.86, 95%CI 1.19-2.91, p = 0.006). The results were stable in the subgroup analysis, with an increased risk in older (> 70 years) or DeBakey type II ATAAD patients. Notably, an increase in the degree and extent of PA-IMH exacerbated the risk of early mortality. However, after landmark analysis at 30-day postsurgery, no significant difference was noted in the long-term outcomes between PA-IMH and non-PA-IMH groups (p = 0.440). The 5-year survival rates were 87.1% (95%CI: 83.3%, 91.1%) and 90.1% (95%CI: 88.5%, 91.7%), respectively. CONCLUSIONS: The presence of PA-IMH in ATAAD patients is common and is independently associated with increased early mortality after surgical repair, especially in those with older age (> 70) or type II dissection. However, such detrimental effects do not persist in the long-term follow-up among patients who survived hospital discharge. CLINICAL RELEVANCE STATEMENT: We confirmed that PA-IMH significantly increases early postoperative mortality in patients with acute type A aortic dissection, especially in older patients or DeBakey type II dissection. This should prompt further investigation of the incremental role of PA-IMH in this pathology. KEY POINTS: Acute type A aortic dissection mortality gets worse when pulmonary artery intramural hematoma is present. Pulmonary artery-intramural hematoma increased the risk of early mortality but not affect long-term prognosis. Further research should investigate the effects of pulmonary artery intramural thrombus on aortic dissection.

The urinary RNA atlas of patients with chronic kidney disease.

Chronic kidney disease (CKD) represents a significant global health burden. Currently employed CKD biomarkers are influenced by various factors and lack accuracy in reflecting early-stage renal fibrosis severity. Consequently, there is an urgent need for the identification of early, noninvasive CKD biomarkers. Urine, easily collectible and kidney-derived, has demonstrated potential as a diagnostic source for various kidney diseases by leveraging its RNA content. To address this, we obtained RNA-seq data pertaining to urinary RNAs from both CKD patients and healthy controls via the Gene Expression Omnibus database (GEO). The DEseq2 software was utilized to identify differentially expressed RNAs (DE-RNAs). To evaluate the overall accuracy of these DE-RNAs in urine, we performed Receiver Operating Characteristic analysis (ROC). Selected urinary RNAs were subsequently validated using reverse-transcription quantitative real-time Polymerase Chain Reaction (qRT-PCR) in conjunction with ROC analysis. Computational and experimental analyses revealed significant increases in miR-542-5p, miR-33b-5p, miR-190a-3p, miR-507, and CSAG4 within the urine of CKD patients, exhibiting high AUC values. In conclusion, our findings suggest that urinary RNAs hold promise as diagnostic biomarkers for CKD.

SNRPD1 inhibition suppresses the proliferation of hepatocellular carcinoma and promotes autophagy through the PI3K/AKT/mTOR/4EBP1 pathway.

BACKGROUND: Small nuclear ribonucleoprotein Sm D1 (SNRPD1) has been reported as an oncogene in some solid cancers. Our previous study suggested that SNRPD1 has diagnostic and prognostic value in hepatocellular carcinoma (HCC), but its role in tumor growth and biological behavior remains unknown. In this study, we aimed to unravel the role and mechanism of SNRPD1 in HCC. METHODS: We investigated the SNRPD1 mRNA level in adjacent normal liver tissues and HCC tissues with different tumor stages in the UALCAN database. The associations between SNRPD1 mRNA expression and HCC prognosis were investigated in TCGA database. Then, 52 pairs of frozen HCC tissues and corresponding adjacent normal liver tissues were collected to perform qPCR and immunohistochemistry assay. Next, we carried out a series of experiments in vitro and in vivo to investigate the effects of SNRPD1 expression on cell invasion, migration, proliferation, autophagy, and the PI3K/AKT/mTOR pathway. RESULTS: The bioinformatics analysis and qPCR in our patient cohort demonstrated that the SNRPD1 mRNA level in HCC tissues was higher than in adjacent normal tissues. In addition, the immunohistochemistry assay exhibited an increased SNRPD1 protein level with the tumor stage increase. Survival analysis suggested that higher expression of SNRPD1 was significantly associated with unfavorable prognosis of patients with HCC. The functional experiments in vitro indicated that SNRPD1 knockdown suppressed the cellular proliferation, migration, and invasion capacities. Furthermore, SNRPD1 inhibition induced cellular apoptosis and arrested the HCC cells at the G0/G1 phase of the cell cycle. Mechanistic analyses demonstrated that SNRPD1 knockdown induced the increase of autophagic vacuoles and the expression of autophagy-related genes (ATG5, ATG7, and ATG12) and blocked the PI3K/AKT/mTOR/4EBP1 pathway in vitro. Moreover, SNRPD1 inhibition suppressed tumor growth and expression of the Ki67 protein in vivo. CONCLUSIONS: SNRPD1 may serve as an oncogene in HCC and promote tumor proliferation via inhibiting autophagy induced through the PI3K/Akt/mTOR/4EBP1 pathway.

Upregulation of lncRNA PTOV1-AS1 in hepatocellular carcinoma contributes to disease progression and sorafenib resistance through regulating miR-505.

Increasing evidence has displayed the vital influence of lncRNA in tumorigenesis and chemoresistance of cancer treatment. This study investigated the function of lncRNA PTOV1-AS1 in hepatocellular carcinoma (HCC) and its role in sorafenib resistance. The relative expression of lncRNA and miRNA was measured by RT-qPCR. The cellular activities including cell proliferation and invasion were explored by CCK-8 and Transwell assays. Bioinformatics analysis and dual-luciferase reporter assay were used to predict the targeting miRNA of PTOV1-AS1. The expression levels of PTOV1-AS1 were higher in HCC tissues than that in the normal tissues and associated with patients' overall survival. Knockdown of PTOV1-AS1 decreased cell proliferation rate and invasion number. After treatment with different concentrations of sorafenib, the sorafenib-resistant hepatoma cells were conducted. PTOV1-AS1 expression levels were increased in HepG2-SR and Huh7-SR cells. PTOV1-AS1 knockdown repressed the proliferation, invasion, and drug resistance of sorafenib-resistant HCC cells by targeting the expression of miR-505. In conclusion, the expression of PTOV1-AS1 is increased in HCC and sorafenib-resistance HCC cells, as well as is associated with patients' prognosis. Inhibition of PTOV1-AS1 expression can reduce the resistance of sorafenib-resistant HCC cells, which may play a role by targeting the negative regulation of miR-505 expression.

A Model of Basement Membrane-Associated Gene Signature Predicts Liver Hepatocellular Carcinoma Response to Immune Checkpoint Inhibitors.

Liver hepatocellular carcinoma (LIHC) is a highly lethal malignant tumor originating from the digestive system, which is a serious threat to human health. In recent years, immunotherapy has shown significant therapeutic effects in the treatment of LIHC, but only for a minority of patients. The basement membrane (BM) plays an important role in the occurrence and development of tumors, including LIHC. Therefore, this study is aimed at establishing a risk score model based on basement membrane-related genes (BMRGs) to predict patient prognosis and response to immunotherapy. First, we defined three patterns of BMRG modification (C1, C2, and C3) by consensus clustering of BMRG sets and LIHC transcriptome data obtained from public databases. Survival analysis showed that patients in the C2 group had a better prognosis, and Gene Set Variation Analysis (GSVA) revealed that the statistically significant pathways were mainly enriched in the C2 group. Moreover, we performed Weighted Correlation Network Analysis (WGCNA) on the above three subgroups and obtained 179 intersecting genes. We further applied function enrichment analyses, and the results demonstrated that they were mainly enriched in metabolism-related pathways. Furthermore, we conducted the LASSO regression analysis and obtained 4 BMRGs (MPV17, GNB1, DHX34, and MAFG) that were significantly related to the prognosis of LIHC patients. We further constructed a prognostic risk score model based on the above genes, which was verified to have good predictive performance for LIHC prognosis. In addition, we analyzed the correlation between the risk score and the tumor immune microenvironment (TIM), and the results showed that the high-risk scoring group tended to be in an immunosuppressed status. Finally, we investigated the relationship between the risk score and LIHC immune function. The results demonstrated that the risk score was closely related to the expression levels of multiple immune checkpoints. Patients in the low-risk group had significantly higher IPS scores, and patients in the high-risk group had lower immune escape and TIDE score. In conclusion, we established a novel risk model based on BMRGs, which may serve as a biomarker for prognosis and immunotherapy in LIHC.

Pre- to postoperative alpha-fetoprotein ratio-based nomogram to predict tumor recurrence in patients with hepatocellular carcinoma.

Background: This study aimed to investigate the role of the alpha fetoprotein (AFP) ratio before and after curative resection in the prognosis of patients with hepatocellular carcinoma (HCC) and to develop a novel pre- to postoperative AFP ratio nomogram to predict recurrence free survival (RFS) for HCC patients after curative resection. Methods: A total of 485 pathologically confirmed HCC patients who underwent radical hepatectomy from January 2010 to December 2018 were retrospectively analyzed. The independent prognostic factors of hepatocellular carcinoma were identified by multivariate COX proportional model analysis, and the nomogram model was constructed. The receiver operating characteristic and the C-index were used to evaluate the accuracy and efficacy of the model prediction, the correction curve was used to assess the calibration of the prediction model, and decision curve analysis was used to evaluate the clinical application value of the nomogram model. Results: A total of 485 HCC patients were divided into the training cohort (n = 340) and the validation cohort (n = 145) by random sampling at a ratio of 7:3. Using X-tile software, it was found that the optimal cut-off value of the AFP ratio in the training cohort was 0.8. In both cohorts, the relapse-free survival of patients with an AFP ratio <0.8 (high-risk group) was significantly shorter than in those with an AFP ratio ≥0.8 (low-risk group) (P < 0.05). An AFP ratio <0.8 was an independent risk factor for recurrence of HCC after curative resection. Based on the AFP ratio, BCLC stage and cirrhosis diagnosis, a satisfactory nomogram was developed. The AUC of our nomogram for predicting 1-, 3-, and 5-year RFS was 0.719, 0.690, and 0.708 in the training cohort and 0.721, 0.682, and 0.681 in the validation cohort, respectively. Furthermore, our model demonstrated excellent stratification as well as clinical applicability. Conclusion: The AFP ratio was a reliable biomarker for tumor recurrence. This easy-to-use AFP ratio-based nomogram precisely predicted tumor recurrence in HCC patients after curative resection.

Bioinformatics analysis and experimental validation of a novel autophagy-related signature relevant to immune infiltration for recurrence prediction after curative hepatectomy.

Hepatocellular carcinoma (HCC) remains imposing an enormous economic and healthcare burden worldwide. In this present study, we constructed and validated a novel autophagy-related gene signature to predict the recurrence of HCC patients. A total of 29 autophagy-related differentially expressed genes were identified. A five-gene signature (CLN3, HGF, TRIM22, SNRPD1, and SNRPE) was constructed for HCC recurrence prediction. Patients in high-risk groups exhibited a significantly poor prognosis compared with low-risk patients both in the training set (GSE14520 dataset) and the validation set (TCGA and GSE76427 dataset). Multivariate cox regression analysis demonstrated that the 5-gene signature was an independent risk factor for recurrence-free survival (RFS) in HCC patients. The nomograms incorporating 5-gene signature and clinical prognostic risk factors were able to effectively predict RFS. KEGG and GSEA analysis revealed that the high-risk group was enriched with multiple oncology characteristics and invasive-related pathways. Besides, the high-risk group had a higher level of immune cells and higher levels of immune checkpoint-related gene expression in the tumor microenvironment, suggesting that they might be more likely to benefit from immunotherapy. Finally, the immunohistochemistry and cell experiments confirmed the role of SNRPE, the most significant gene in the gene signature. SNRPE was significantly overexpressed in HCC. After SNRPE knockdown, the proliferation, migration and invasion ability of the HepG2 cell line were significantly inhibited. Our study established a novel five-gene signature and nomogram to predict RFS of HCC, which may help in clinical decision-making for individual treatment.

Clinical Results of a Modified Doty's Technique for Supravalvular Aortic Stenosis.

This study aimed to assess the early and mid-term results of the modified Doty's technique compared with the traditional Doty's technique in patients with congenital supravalvular aortic stenosis (SVAS). We retrospectively included 73 consecutive SVAS patients in Beijing and Yunnan Fuwai Hospitals between 2014 and 2021. Patients were divided into the modified technique (n = 9) and the traditional technique group (n = 64). The modified technique involves altering the right head of the symmetrical inverted pantaloon-shaped patch into an asymmetrical triangular form to prevent compression of the right coronary artery ostium. The primary safety outcome was in-hospital surgery-related complications and the primary effectiveness outcome was re-operation at follow-up. The Mann-Whitney U test and Fisher's exact test were used to test the group difference. The median age at operation was 50 months (IQR 27.0-96.0). Twenty-two (30.1%) of the patients were female. The median follow-up was 23.5 months (IQR 3.0-46.0). No in-hospital surgery-related complications and follow-up re-operation occurred in the modified technique group, but the traditional technique group had 14 (21.8%) surgery-related complications and 5 (7.9%) re-operation. Patients with the modified technique had a well-developed aortic root and no aortic regurgitation occurred. A modified technique could be considered for patients with poor aortic root development to reduce postoperative surgery-related complications.

Effectiveness and Safety of Mitral Valve Plasty in Patients with an Anomalous Origin of the Coronary Artery from the Pulmonary Artery.

The study aimed to determine the effectiveness and safety of anomalous coronary artery from pulmonary artery (ACAPA) patients with moderate or severe mitral valve regurgitation (MVR) receiving mitral valve plasty (MVP) concurrently. Consecutive ACAPA patients undergoing surgery between 2015 and 2021 were retrospectively included. Patients were divided into three groups: moderate MVR without MVP (non-MVP (moderate) N = 14), moderate MVR with MVP (MVP (moderate) N = 13), and severe MVR with MVP (MVP (severe) N = 13). The primary safety endpoint was in-hospital surgery-related complications. The primary effectiveness outcome was left ventricular ejection function (LVEF) and left ventricular end-diastolic diameter (LVEDD) z-score at 2- and 24-month follow-ups. Multivariable linear regression models were used to obtain the ß coefficient. The median age of the included patients was 7.5 years (IQR 1.4-26.5). The in-hospital surgery-related complication rates were 7.1%, 15.4%, and 7.7% in non-MVP (moderate), MVP (moderate), and MVP (severe) groups, separately. At the 2-month follow-up, the non-MVP (moderate) group had a better LVEF and LVEDD z-score compared with the MVP (moderate) group (LVEF ß = 9.22, 95%CI 1.09 to 17.35; LVEDD z-score ß = -2.49, 95%CI -4.53 to -0.45). At the 24-month follow-up, the LVEF of all patients and the LVEDD z-score of 90% of patients in the three groups returned to normal. For ACAPA patients with moderate MVR, MVP was not necessary, especially for pediatric patients (age < 3 years) and patients with secondary MVR. Further studies for ACAPA patients with severe MVR are still needed.

HMGB1/TLR4 signaling pathway enhances abdominal aortic aneurysm progression in mice by upregulating necroptosis.

OBJECTIVE AND DESIGN: The age-associated increases in aseptic inflammation and necroptosis are closely related to the emergence of various age-associated diseases. METHODS: In this study, the role of HMGB1/TLR4-induced necroptosis in abdominal aortic aneurysm (AAA) formation was investigated. First, the levels of sterile inflammatory mediators (HMGB1, TLR4) and necroptosis markers were measured in the abdominal aortas of young and old C57BL/6JNifdc mice. We observed that sterile inflammatory mediators and necroptosis markers were greatly increased in the abdominal aortas of old mice. Then, angiotensin II (Ang II)-induced AAA model in APOE-/- mice was used in this study. Mice AAA models were treated with the RIP1 inhibitor necrostatin-1 (Nec-1) or the TLR4 inhibitor TAK-242, respectively. RESULTS: We found that HMGB1, TLR4, and necroptosis markers were elevated in old mice compared with those in young mice. Same elevation was also found in the development of AAA in APOE-/- mice. In addition, the necroptosis inhibitor Nec-1 alleviated Ang II-induced AAA development while downregulating the expression of HMGB1/TLR4. After blocking TLR4 with TAK-242, the expression of necroptosis markers decreased significantly, and the progression of AAA was also alleviated in APOE-/- mice. CONCLUSIONS: Our results indicated that HMGB1/TLR4-mediated necroptosis enhances AAA development in the Ang II-induced AAA model in APOE-/- mice and that TLR4 might be a potential therapeutic target for AAA management.

BZW2, CDT1 and IVD Act As Biomarkers for Predicting Hepatocellular Carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is the leading cause of cancer-related deaths globally. This study aimed to provide a comprehensive investigation to screen and identify biomarkers for predicting HCC. METHODS: Firstly, the bioinformatics technique was applied to screen potential HCC-related genes, and the relationships between BZW2, CDT1, IVD expression and survival rate and clinicopathological factors were assessed. Afterward, qRT-PCR, western blot and immunohistochemistry were employed to validate the expression of BZW2, CDT1, and IVD in clinical resected cancer specimens. Furthermore, in vitro assays, cell cycle, apoptosis, colony formation and scratch experiments were performed to detect the effects of si-BZW2, si-CDT1 and oe-IVD in HCC cells. In vivo experiments, tumor volume and weight were measured to assess the anti-tumor effect of si-BZW2, si-CDT1 and oe-IVD in HCCtumor- bearing mice. RESULTS: Bioinformatics analysis indicated that HCC patients with high expression of BZW2, CDT1 and low expression of IVD have a poor prognosis and unfavorable clinicopathological factors. Similarly, clinical sample analysis revealed that BZW2 and CDT1 expression were increased while IVD expression was decreased in HCC tissues. Meanwhile, in vitro experiments found that si-BZW2, si- CDT1 and oe-IVD promoted apoptosis and inhibited the colony formation and migration of HCC cells. As expected, in vivo experiments demonstrated that si-BZW2, si-CDT1 and oe-IVD could inhibit tumor growth. CONCLUSION: Increased BZW2, CDT1 levels, and decreased IVD levels could act as biomarkers for predicting HCC. Furthermore, targeting BZW2, CDT1, and IVD may offer a new approach to treat HCC.

Assessment of three types of surgical procedures for supravalvar aortic stenosis: A systematic review and meta-analysis.

Importance: The safety and efficacy of different surgical repairs of supravalvar aortic stenosis (SVAS) are inconsistent. Objective: To compare the prognosis of single-, two- and three-patch repair for patients with SVAS. Data sources: PubMed, EMBASE, Cochrane Library, Web of Science, and clinicaltrials.gov were searched until April 17, 2022. Study selection: Study reported SVAS patients treated with single-, two- or three-patch repair. Data extraction and synthesis: Two reviewers independently extracted the data of study characteristics and clinical outcomes. Multiple pairwise and frequentist network meta-analyses were conducted. And a fixed-effect model was used when no heterogeneity existed. Main outcomes and measures: Outcomes included the rate of reintervention, aortic insufficiency, early mortality and late mortality, cardiopulmonary bypass (CPB) time, cross-clamping (CCP) time, and postoperative/ follow-up pressure gradient. Binary variables were evaluated by odds ratio (OR) and its 95% confidence interval (CI), while continuous variables were assessed by standardized mean difference (SMD) and its 95% CI. Results: Twenty-seven retrospective cohort studies were included, comprising 1,162 patients, undergoing single-patch (46.6% of cases), two-patch (33.9%), and three-patch repair (19.4%). Two-patch method had a lower rate of reintervention compared with single-patch (OR = 0.47, 95 % CI 0.28-0.89), and three-patch (OR = 0.31, 95 % CI 0.15-0.64). This finding also applied to juvenile and non-Asian patients. Three-patch method had a lower rate of aortic insufficiency compared with single-patch (OR = 0.11, 95 % CI 0.01-0.63), and two-patch (OR = 0.11, 95 % CI 0.02-0.83). But this repair had the longest CCP time, which was significantly longer than that of single- (SMD = 0.76, 95 % CI 0.36-1.17) or two-patch repair (SMD = 0.61, 95 % CI 0.06-1.16). No significant difference was found in mortality and pressure gradient among three procedures. Conclusion and relevance: Two-patch repair has the lowest reintervention rate and relatively reasonable operation time. Complex and severe SVAS is suggested to be treated with two-patch repair. Further prospective studies of a reasonable sample size will be required with a special focus on the use of different patch materials and surgeons' unique working experience. Systematic review registration: http://www.crd.york.ac.uk/PROSPERO/, identifier: CRD42022328146.

miR-517b-3p promotes the progression of portal vein tumor thrombus via activating Wnt/ß-catenin signaling pathway in hepatocellular carcinoma.

AIMS: This study was aimed to investigate the expression patterns and prognostic value of microRNA-517b-3p (miR-517b-3p) in hepatocellular carcinoma (HCC) patients with portal vein tumor thrombus (PVTT). METHODS: The expression of miR-517b-3p in PVTT tissues and cells was estimated using qRT-PCR. Through Kaplan-Meier survival analysis, Cox regression assay and ROC analysis, the significance of miR-517b-3p was explored. In addition, cell experiments were performed to examine the functional role of miR-517b-3p during progression of PVTT. Moreover, the biological process and biological pathway analysis analyses were conducted through GSEA and FunRich. Besides, the protein-protein interaction (PPI) network of the DEGs was established through cBioPortal website. RESULTS: Compared with the controls, the miR-517b-3p was upregulated in both PVTT tissues and cells. The upregulated miR-517b-3p, which served as a potential diagnostic biomarker to distinguish PVTT from PT and controls, was associated with poor overall survival and acted as an independent prognostic factor. The cell proliferation, migration and invasion were proved to be enhanced by overexpression of miR-517b-3p. Furthermore, Wnt/ß-catenin signaling was suppressed by miR-517b-3p knockdown and might be involved in the progression of PVTT. CONCLUSION: miR-517b-3p may promote PVTT cell proliferation, migration and invasion via activation of Wnt/ß-catenin signaling pathway. Meanwhile, miR-517b-3p has overexpression in PVTT samples, and serves as a candidate diagnostic and prognostic biomarker in HCC patients with PVTT.

Orthotopic liver transplantation improves postoperative quality of life, survival rate and reduces recurrence rate in patients with liver cancer.

OBJECTIVE: To evaluate the impact of orthotopic liver transplantation (OLT) on postoperative quality of life (QoL), survival rate and recurrence rate of patients with liver cancer (LC). METHODS: One hundred and twenty-seven patients with LC treated in our hospital from December 2016 to January 2018 were divided into two groups according to different treatment schemes. Patients in the research group (n=67) were given OLT and those in the control group (n=60 cases) were given hepatectomy. The incidence of postoperative complications, hospitalization expenses, the time to liver function recovery, surgical wound healing, pain resolution and hospitalization were compared between the two groups. The overall survival rate (OSR), disease-free survival rate (DFSR), and average survival time of patients were recorded and compared. The Visual Analogue Scale (VAS) score one day and three days after surgery, alpha-fetoprotein (AFP) level, and adverse emotion before and after operation were compared. QoL scores at six months after surgery, one-year recurrence and metastasis rates, and treatment satisfaction one year after surgery were also compared. The expression of Ki-67 and Topo IIαin the tumor-bearing group (n=5) was detected. RESULTS: The research group presented markedly lower incidence of postoperative complications, and evidently shorter time to liver function recovery, surgical wound healing, pain resolution and hospitalization, while with noticeably higher hospitalization expenses. The one-year and five-year OSRs and DFSRs were noticeably higher, and the average survival time was remarkably longer in the research group as compared to the control group. Patients in the research group scored remarkably lower in VAS scores on the first and third day after surgery than patients in the control group. In comparison with the control group, the one-year recurrence and metastasis rates were evidently lower in the research group, and the scores of SF-36 were remarkably higher. The AFP level at one month after surgery was obviously lower in the research group, and the treatment satisfaction was greatly higher. Ki-67 in the tumor-bearing group was mainly located in the nucleus, and Topo IIα was mainly nucleus positive; the positive Ki-67 and Topo IIα expression rates in the tumor-bearing group was 66.7% and 69.8%, respectively. CONCLUSIONS: OLT can improve the postoperative QoL, survival rate and reduce the recurrence rate of LC patients.

The Oncogenic and Diagnostic Potential of Stanniocalcin 2 in Hepatocellular Carcinoma.

Purpose: Early detection and prognostic prediction of hepatocellular carcinoma (HCC) remain a great challenge. In this study, we explored the role and diagnostic significance of stanniocalcin 2 (STC2), recently identified as a secretory protein, in HCC. Methods: STC2 mRNA and protein in HCC tissues were examined by qRT-PCR and immunohistochemistry. The regulatory role of HCC growth by STC2 was evaluated in vitro and in vivo. Serum STC2 levels were determined in HCC patients and compared to those with liver cirrhosis (LC) and normal controls (NC). The difference and significance of STC2 levels between groups were analyzed by Mann-Whitney U-test. The diagnostic value of serum STC2 in detecting early HCC was assayed with receiver operating characteristics (ROC). The association of STC2 with overall survival (OS) was determined with Kaplan-Meier method. Results: STC2 was elevated in about 77.1% HCC patients and correlated with advanced tumor progression. Overexpression or knockdown of STC2 stimulated or suppressed HCC colony formation and xenograft tumor growth. AKT activation played a critical role in tumor-promoting effect of STC2. The median level of serum STC2 in HCC patients (n = 98, 2086.6 ng/L) was 2.6-fold and 4.2-fold that in LC patients (n = 42, 801.9 ng/L) and NC (n = 26, 496.9 ng/L), respectively. A cut-off value 1493 ng/L for STC2 could distinguish early HCC from LC with a sensitivity of 76.9% and a specificity of 76.2%, both of which were superior to AFP at 20 µg/L (sensitivity 69.2%, specificity 52.4%). STC2 was positive in 77.8% (14/18) AFP-negative patients. High STC2 level was correlated with poor overall and disease specific survival. Conclusion: STC2 is upregulated in both tumor and serum of HCC patients, and its overexpression promotes HCC via AKT pathway. STC2 possesses a diagnostic significance and may serve as an auxiliary biomarker of AFP for detecting early HCC.

Immune Analysis and Small Molecule Drug Prediction of Hepatocellular Carcinoma Based on Single Sample Gene Set Enrichment Analysis.

Though patients with hepatocellular carcinoma (HCC) benefit from the treatment of immune checkpoint inhibitor (ICB), it is still of vital significance to develop more effective drugs and predict patients' response to ICB therapy. Herein, we utilized single sample gene set enrichment analysis (ssGSEA) to score the downloaded tumor samples from TCGA-LIHC based on 29 immune gene sets, thus reflecting the immunologic competence of samples. Then samples were classified into high, moderate, and low immunity groups. Additionally, we utilized survival analysis and ESTIMATE score to verify the reliability of the immunity grouping. We then performed differential expression analysis on the samples in these two groups and obtained 716 differentially expressed genes (DEGs). Next, the DEGs mentioned above were subjected to GO and KEGG analyses. The outcomes demonstrated that these DEGs were mostly correlated with the immune-related biological functions. To further verify biological processes in which DEGs might be involved, we constructed a protein-protein interaction network. Afterward, we used MCODE plugin to conduct subnetwork analysis. Thereafter, KEGG enrichment analysis was performed on two genes with the highest score in the subnetwork. The results exhibited that these genes were gathered in pathways such as Th1 and Th2 cell differentiation and NF-κB. Finally, we utilized Connectivity Map to find possible drugs for the treatment of HCC and obtained complex methyl-angolensate. The above results may contribute to distinguishing HCC patients who are eligible for immunotherapy and providing the foundations for the development of therapeutic drugs for HCC.

Overexpression of chaperonin containing TCP1 subunit 7 has diagnostic and prognostic value for hepatocellular carcinoma.

Chaperonin containing TCP1 subunit 7 (CCT7) regulates the expression of many tumor-related proteins. We investigated the diagnostic and prognostic value of CCT7 expression for hepatocellular carcinoma (HCC). In datasets from The Cancer Genome Atlas and the Gene Expression Omnibus, CCT7 mRNA levels were greater in HCC tissues than adjacent normal tissues, and these results were validated using immunohistochemistry. In patients with early-stage disease and low alpha-fetoprotein expression, CCT7 expression was still higher in HCC tissues than normal tissues. Receiver operating characteristic curve analyses indicated that CCT7 expression had better diagnostic value than alpha-fetoprotein for HCC patients with early-stage disease and low alpha-fetoprotein expression. The positive predictive value of CCT7 expression was higher than that of alpha-fetoprotein expression. Higher CCT7 mRNA and protein levels were independent risk factors for poorer overall and recurrence-free survival in HCC patients. Greater methylation of the CpG site cg19515186 was associated with better overall survival in HCC patients. Genes co-expressed with CCT7 were upregulated in HCC and associated with poorer overall survival. Gene Ontology, Kyoto Encyclopedia of Genes and Genomes and Gene Set Enrichment Analyses demonstrated that CCT7 expression correlated with spliceosome signaling. These findings demonstrate that CCT7 has diagnostic and prognostic value for HCC.

The diagnostic and prognostic significance of small nuclear ribonucleoprotein Sm D1 aberrantly high expression in hepatocellular carcinoma.

Small nuclear ribonucleoprotein Sm D1 (SNRPD1), one of the crucial genes encoding core spliceosome components, was abnormally highly expressed in multiple types of tumors. In this study, we investigated the diagnostic and prognostic significance of SNRPD1 in hepatocellular carcinoma (HCC). The investigation of datasets from GEO and TCGA databases revealed that SNRPD1 expression in HCC was significantly higher than adjacent normal liver tissues, which was validated by immunohistochemistry (IHC). Both GO, KEGG analysis showed that the SNRPD1 co-expressed genes mainly enriched in Cell division, Nuclear import, mRNA splicing via spliceosome, Ribosome, Cell cycle, etc. Survival analysis from the GSE14520 dataset and 154 HCC cohorts exhibited a significant association of high SNRPD1 expression with poor overall survival and recurrence-free survival. ROC analysis showed that the abnormally high SNRPD1 mRNA expression has diagnostic significance in distinguishing between HCC and normal liver tissue (AUC = 0.819). Gene set enrichment analysis (GSEA) demonstrated that the high expression of SNRPD1 might regulate HCC tumorigenesis and progression by affecting the cell cycle, mismatch repair, DNA replication, and RNA degradation, etc. The luciferase report assay revealed that SNRPD1 was the direct target gene of miR-100 manifested by decreased SNRPD1 expression and luciferase activity in the HCC cells upon miR-100 overexpression. Finally, SNRPD1 may as an oncogene affecting the progression of HCC through regulates the mTOR pathway and autophagy.