High Postoperative Recurrence Rate Research Articles

Construction of Novel lncRNA-miRNA-mRNA Network Associated With Recurrence and Identification of Immune-Related Potential Regulatory Axis in Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is one of the most common malignant diseases globally. Despite continuous improvement of treatment methods, high postoperative recurrence rate remains an urgent problem. In order to determine the mechanism underlying recurrence of liver cancer and identify prognostic genes, data from the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) were integrated and analyzed. Differentially expressed genes (DEGs) between HCC tissue and normal liver tissue were identified, and a protein–protein interaction network was constructed to find hub genes. Clinical correlation analysis and disease-free survival (DFS) analysis were performed using the R language and GEPIA to identify relapse-related genes. Correlation analysis was used to identify a potential regulatory axis. Dual-luciferase reporter gene assay was used to confirm the reliability of the long non-coding RNA (lncRNA)–microRNA (miRNA)–mRNA regulatory axis. Immune infiltration analysis was performed using the TIMER database. Correlations between immune gene markers and ASF1B were verified using quantitative real-time polymerase chain reaction (RT-qPCR). In this work, we found that nine lncRNAs and five mRNAs were significantly overexpressed in HCC tissues from patients with recurrence. SNHG3, LINC00205, ASF1B, AURKB, CCNB1, CDKN3, and DTL were also closely related to HCC grade and stage. Survival analysis showed that these seven DEGs were significantly correlated with poor DFS. Correlation analysis identified SNHG3–miR-214-3p–ASF1B as a potential regulatory axis. Dual-luciferase reporter gene assay showed that SNHG3 and ASF1B directly bound to miR-214-3p. ASF1B was negatively regulated by miRNA-214-3p, and overexpression of SNHG3 could inhibit the expression of miRNA-214-3p. In addition, ASF1B was positively correlated with immune infiltration. A reduction in ASF1B could markedly inhibit the expression of CD86, CD8, STAT1, STAT4, CD68, and PD1 in HCC cells. Flow cytometry showed that SNHG3 promoted the PD-1 expression by regulating ASF1B. Meanwhile, elevated ASF1B predicted poor prognosis of HCC patients in subgroups with decreased B cells, CD8+ T cells, or neutrophils, and those with enriched CD4+ T cells. In conclusion, we found that a novel lncRNA SNHG3/miR-214-3p/ASF1B axis could promote the recurrence of HCC by regulating immune infiltration.

MiR-296-5p ameliorates deep venous thrombosis by inactivating S100A4.

Deep venous thrombosis is one of the most common venous thromboembolic diseases and has a low cure rate and a high postoperative recurrence rate. Furthermore, emerging evidence indicates that microRNAs are involved in deep venous thrombosis. miR-296-5p is an important microRNA that plays a critical role in various cellular functions, and S100A4 is closely related to vascular function. miR-296-5p is downregulated in deep venous thrombosis patients, and its predicted target S100A4 is upregulated in deep venous thrombosis patients. Therefore, it was hypothesized that miR-296-5p may play a vital role in the development of deep venous thrombosis by targeting S100A4. An Ox-LDL-stimulated HUVEC and deep venous thrombosis mouse model was employed to detect the biological functions of miR-296-5p and S100A4. Dual luciferase reporter assays and pull-down assays were used to authenticate the interaction between miR-296-5p and S100A4. ELISA and Western blotting were employed to detect the protein levels of thrombosis-related factors and the endothelial-to-mesenchymal transition (EndMT)-related factors. The miR-296-5p levels were reduced, while the S100A4 levels were enhanced in deep venous thrombosis patients, and the miR-296-5p levels were negatively correlated with the S100A4 levels in deep venous thrombosis patients. miR-296-5p suppressed S100A4 expression by targeting the 3' UTR of S100A4. MiR-296-5p knockdown accelerated ox-LDL-induced HUVEC apoptosis, oxidative stress, thrombosis-related factor expression, and EndMT, while S100A4 knockdown antagonized these effects in ox-LDL-induced HUVECs. S100A4 knockdown reversed the effect induced by miR-296-5p knockdown. Moreover, the in vivo studies revealed that miR-296-5p knockdown in deep venous thrombosis mice exacerbated deep venous thrombosis formation, whereas S100A4 knockdown had the opposite effect. These results indicate that elevated miR-296-5p inhibits deep venous thrombosis formation by inhibiting S100A4 expression. Both miR-296-5p and S100A4 may be potential diagnostic markers and therapeutic targets for deep venous thrombosis.

Co-amplification of genes in chromosome 8q24: a robust prognostic marker in hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is a leading cause of tumor-associated death worldwide, owing to its high 5-year postoperative recurrence rate and inter-individual heterogeneity. Thus, a prognostic model is urgently needed for patients with HCC. Several researches have reported that copy number amplification of the 8q24 chromosomal region is associated with low survival in many cancers. In the present work, we set out to construct a multi-gene model for prognostic prediction in HCC. RNA sequencing and copy number variant data of tumor tissue samples of HCC from The Cancer Genome Atlas (n=328) were used to identify differentially expressed messenger RNAs of genes located on the chromosomal 8q24 region by the Wilcox test. Univariate Cox and Lasso-Cox regression analyses were carried out for the screening and construction of a prognostic multi-gene signature in The Cancer Genome Atlas cohort (n=119). The multi-gene signature was validated in a cohort from the International Cancer Genome Consortium (n=240). A nomogram for prognostic prediction was built, and the underpinning molecular mechanisms were studied by Gene Set Enrichment Analysis. We successfully established a 7-gene prognostic signature model to predict the prognosis of patients with HCC. Using the model, we divided individuals into high-risk and low-risk sets, which showed a significant difference in overall survival in the training dataset (HR =0.17, 95% CI: 0.1-0.28; P<0.001) and in the testing dataset (HR = 0.42, 95% CI: 0.23-0.74; P=0.002). Multivariate Cox regression analysis showed the signature to be an independent prognostic factor of HCC survival. A nomogram including the prognostic signature was constructed and showed a better predictive performance in short-term (1 and 3 years) than in long-term (5 years) survival. Furthermore, Gene Set Enrichment Analysis identified several pathways of significance, which may aid in explaining the underlying molecular mechanism. Our 7-gene signature is a reliable prognostic marker for HCC, which may provide meaningful information for therapeutic customization and treatment-related decision making.

ESR1 as a recurrence-related gene in intrahepatic cholangiocarcinoma: a weighted gene coexpression network analysis

BackgroundIntrahepatic cholangiocarcinoma (iCCA) is the second most common malignant hepatic tumor and has a high postoperative recurrence rate and a poor prognosis. The key roles of most tumor recurrence-associated molecules in iCCA remain unclear. This study aimed to explore hub genes related to the postsurgical recurrence of iCCA.MethodDifferentially expressed genes (DEGs) between iCCA samples and normal liver samples were screened from The Cancer Genome Atlas (TCGA) database and used to construct a weighted gene coexpression network. Module-trait correlations were calculated to identify the key module related to recurrence in iCCA patients. Genes in the key module were subjected to functional enrichment analysis, and candidate hub genes were filtered through coexpression and protein–protein interaction (PPI) network analysis. Validation studies were conducted to detect the “real” hub gene. Furthermore, the biological functions and the underlying mechanism of the real hub gene in iCCA tumorigenesis and progression were determined via in vitro experiments.ResultsA total of 1019 DEGs were filtered and used to construct four coexpression modules. The red module, which showed the highest correlations with the recurrence status, family history, and day to death of patients, was identified as the key module. Gene Ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses demonstrated that genes in the red module were enriched in genes and pathways related to tumorigenesis and tumor progression. We performed validation studies and identified estrogen receptor 1 (ESR1), which significantly impacted the prognosis of iCCA patients, as the real hub gene related to the recurrence of iCCA. The in vitro experiments demonstrated that ESR1 overexpression significantly suppressed cell proliferation, migration, and invasion, whereas ESR1 knockdown elicited opposite effects. Further investigation into the mechanism demonstrated that ESR1 acts as a tumor suppressor by inhibiting the JAK/STAT3 signaling pathway.ConclusionsESR1 was identified as the real hub gene related to the recurrence of iCCA that plays a critical tumor suppressor role in iCCA progression. ESR1 significantly impacts the prognosis of iCCA patients and markedly suppresses cholangiocarcinoma cell proliferation, migration and invasion by inhibiting JAK/STAT3 signaling pathway.

Recent Advances and Future Directions of Diagnostic and Prognostic Prediction Models in Ovarian Cancer

Ovarian cancer has one of the highest mortality rates among gynecological malignancies. This disease has a low early detection rate, a high postoperative recurrence rate, and a 5-year survival rate of only 40%. Hence, there is an urgent need to improve the early diagnosis and prognosis of ovarian cancer. Prediction models can effectively estimate the risk of disease occurrence, as well as its prognosis. Recently, many studies have established multiple ovarian cancer prediction models based on different regions and populations. These models can improve the detection rate and optimize the prognosis management to a certain extent. Herein, the construction principle of the ovarian cancer risk prediction model and its validation are summarized; furthermore, comprehensive reviews and comparisons of the different types of these models are made. Therefore, our review may be of great significance for the whole course of ovarian cancer management.

LncRNA HAND2-AS1 suppressed the growth of triple negative breast cancer via reducing secretion of MSCs derived exosomal miR-106a-5p.

Background: Triple-negative breast cancer (TNBC) is a special type of breast cancer, its tumor cell metastasis rate is much higher than other types, and at the same time has a high rate of postoperative recurrence, which significantly threatens the health of women. Thus, it is urgent to explore a new treatment for TNBC.Results: MiR-106a-5p was up-regulated in TNBC tissues and cells, and was positively correlated with the tumor grade, which indicated poor prognosis in TNBC patients. Mesenchymal stem cells (MSCs) can transport miR-106a-5p into TNBC cells via exosomes. Functional analysis showed exo-miR-106a-5p secreted by MSCs promoted tumor progression in TNBC cells. Furthermore, lncRNA HAND2-AS1 inhibited miR-106a-5p levels, and HAND2-AS1 was decreased in TNBC tissues and cells. Besides, overexpression of HAND2-AS1 reduced the secretion of exo-miR-106a-5p secretion from MSCs, thus suppressed TNBC development.Conclusion: Our study revealed that HAND2-AS1 inhibited the growth of TNBC, which were mediated by the inhibitory effects of MSC-derived exosomal miR-106a-5p.

Comparison of Percutaneous Endoscopic Lumbar Discectomy with Minimally Invasive Transforaminal Lumbar Interbody Fusion as a Revision Surgery for Recurrent Lumbar Disc Herniation after Percutaneous Endoscopic Lumbar Discectomy.

ObjectiveThe purpose of this study was to compare the outcomes between percutaneous endoscopic lumbar discectomy (PELD) and minimally invasive transforaminal lumbar interbody fusion (MIS-TLIF) for the revision surgery for recurrent lumbar disc herniation (rLDH) after PELD surgery.Patients and MethodsA total of 46 patients with rLDH were retrospectively assessed in this study. All the patients had received a PELD in Peking University First Hospital between January 2015 and June 2019, before they underwent a revision surgery by either PELD (n=24) or MIS-TLIF (n=22). The preoperative data, perioperative conditions, complications, recurrence condition, and clinical outcomes of the patients were compared between the two groups.ResultsCompared to the MIS-TLIF group, the PELD group had significantly shorter operative time, less intraoperative hemorrhage, and shorter postoperative hospitalization, but higher recurrence rate (P<0.05). Complication rates were comparable between the two groups. Both groups had satisfactory clinical outcomes at a 12-month follow-up after the revision surgery. The PELD group also showed significantly lower visual analog scale (VAS) scores of back pain and Oswestry disability index (ODI) in one month after the revision surgery, whereas the difference was not detectable at six- and 12-month follow-ups.ConclusionBoth PELD and MIS-TLIF are effective as a revision surgery for rLDH after primary PELD. PELD is superior to MIS-TLIF in terms of operative time amount of intraoperative hemorrhage and postoperative hospitalization. However, its higher postoperative recurrence rate must be considered and patients should be well informed, when making a decision between the two surgical approaches.

Advances in perioperative systemic therapy for hepatocellular carcinoma

The low surgical resection rate and high postoperative recurrence rate of hepatocellular carcinoma(HCC) are urgent clinical problems to be solved. Therefore, it is important to develop effective perioperative treatment. In recent years, a growing number of studies have shown that systemic therapy is expected to break through the limitations of traditional local treatment and play an important role in preoperative treatment. For example, some novel targeted agents and immunocheckpoint inhibitors have shown excellent potential as neoadjuvant treatment for HCC. Meanwhile, researchers have explored the application of systemic therapy as adjuvant therapy, but due to different criteria for patient selection, no consensus is reached on its efficacy. By far, there is no standard procedure for the application of systemic therapy in HCC perioperative period, little is known about the efficacy and safety of targeted drugs and immunotherapy. This article discusses the feasibility of systemic therapy as neoadjuvant and adjuvant treatment of HCC, as well as its adverse events, with an aim to provide new horizons of HCC systemic therapy in the perioperative period.

Application of Absolute Alcohol in the Treatment of Traumatic Intracranial Hemorrhage via Interventional Embolization of Middle Meningeal Artery.

Background: Traumatic brain injury is a common condition in neurosurgery. Traditional methods of treatment include conservative treatment and surgical evacuation using burr-holes or craniotomy; however, studies have reported problems such as high re-expansion rates after conservative treatment of epidural hematoma and high postoperative recurrence rates of subdural hematoma. Solutions to these problems are lacking, and research into new treatment methods is ongoing. Among the potential new treatments, middle meningeal arterial embolization is an option. This study involved patients with acute epidural hematoma and chronic subdural hematoma. The purpose was to evaluate the use and effects of absolute alcohol to embolize the middle meningeal artery to treat intracranial hematoma.Material and Methods: A retrospective description study was 12 cases of intracranial hematoma who treated with absolute alcohol interventional therapy from our hospital between June 2018 and October 2019. Five patients with acute epidural hematoma and seven patients with chronic subdural hematoma were treated using absolute alcohol to embolize the middle meningeal artery. Patients' clinical data, imaging results, surgical results, and prognosis were recorded and analyzed.Results: All patients underwent absolute alcohol embolization of the middle meningeal artery, in combination with burr-hole drainage. All imaging data were confirmed preoperatively. We successfully used absolute alcohol to embolize the middle meningeal artery intraoperatively and confirmed these results by postoperative angiography. All patients achieved symptomatic relief without complications, and no recurrence or re-expansion was seen with follow-up computed tomography. Our study has been registered in the Chinese Clinical Trial Registry (http://www.chictr.org.cn, ChiCTR1800018714).Conclusion: The use of absolute alcohol to embolize the middle meningeal artery could be used as an attempt to treat acute epidural hematoma and chronic subdural hematoma.

Circulating tumor cells are an indicator for the administration of adjuvant transarterial chemoembolization in hepatocellular carcinoma: A single-center, retrospective, propensity-matched study.

BackgroundHigh rates of postoperative tumor recurrence contribute to poor outcome in hepatocellular carcinoma (HCC). Here, we investigated whether circulating tumor cells (CTCs) status can predict the benefit of adjuvant transcatheter arterial chemoembolization (TACE) in patients with HCC.MethodsThe retrospective study enrolled 344 HCC patients with preoperative CTCs analysis. Clinical outcomes including recurrence and survival were compared between those who received and who did not receive adjuvant TACE. Similar comparisons were made for patients stratified according to CTC status (CTC‐negative [CTC = 0], n = 123; CTC‐positive [CTC ≥ 1], n = 221). Propensity score matching (PSM) strategy was adopted to offset differences between two groups.ResultsIn the study cohort as a whole or in CTC‐negative cohort, there were no observable differences in overall survival (OS) or time to recurrence (TTR) between TACE and control group (P > .05). In CTC‐positive patients, PSM generated 64 patient pairs, and patients with adjuvant TACE had significantly better clinical outcomes (OS: not reached vs 36.4 months, P < .001; TTR: 45.8 vs 9.8 months, P < .001). Adjuvant TACE significantly reduced early recurrence (≤2 years) (64.1% vs 31.7%, P < .001) in CTC‐positive patients. Notably, adjuvant TACE influenced TTR and OS even in subgroups of CTC‐positive patients with low risk of recurrence according to traditional evaluation.ConclusionsPreoperative CTC status could serve as an indicator for the administration of adjuvant TACE in HCC patients. Adjuvant TACE benefits CTC‐positive HCC patients mainly by reducing early recurrence.

The Roles of Glycans in Bladder Cancer.

Bladder cancer is one of the most common malignant tumors of the urogenital system with high morbidity and mortality worldwide. Early diagnosis and personalized treatment are the keys to successful bladder cancer treatment. Due to high postoperative recurrence rates and poor prognosis, it is urgent to find suitable therapeutic targets and biomarkers. Glycans are one of the four biological macromolecules in the cells of an organism, along with proteins, nucleic acids, and lipids. Glycans play important roles in nascent peptide chain folding, protein processing, and translation, cell-to-cell adhesion, receptor-ligand recognition, and binding and cell signaling. Glycans are mainly divided into N-glycans, O-glycans, proteoglycans, and glycosphingolipids. The focus of this review is the discussion of glycans related to bladder cancer. Additionally, this review also addresses the clinical value of glycans in the diagnosis and treatment of bladder cancer. Abnormal glycans are likely to be potential biomarkers for bladder cancer.

Surgical Experience of Behcet's Disease Involving the Peripheral Artery

Behcet's disease with arterial involvement shows rapid poor progression compared with Behcet's disease without arterial involvement, such that it may be thought of as a different disease. With arterial involvement, high rates of postoperative recurrence and anastomotic complications are observed. The medical records of 1,361 patients diagnosed with Behcet's disease who visited our hospital from January 2007 to December 2019 were reviewed. Overall, 118 patients with blood vessel involvement were considered. Those with only vein involvement, intracerebral arterial involvement, and coronary arterial involvement were excluded. The 8 patients who underwent surgical treatments and the 9 patients who underwent conservative treatments were included and reported in this study. The mean age and mean follow-up duration of the 17 patients with peripheral arterial involvement were 49.82±13.24years and 89.85±52.70months, respectively. In all cases where the operations were performed, the first operation was an emergency operation for rupture of the aneurysm, impending sign of rupturing, or acute ischemia. Eight patients received a total of 18 operations. The average number of operations per patient and the reoperation rate were 2.25±0.89 times and 75%, respectively. The 5-year and 10-year survival rates of the patients who underwent surgery were 75.0% and 30.0%, respectively. When arterial involvement occurs in the form of an aneurysm, the hazard ratio for death is 9.644 (P=0.040, confidence interval 1.11-83.74). When the artery invades in the form of an aneurysm, the mortality rate is higher regardless of surgery. The main cause of mortality is complications that occur in the anastomosis sites after the operation. Postoperative short-term and regular imaging of the anastomosis area can be beneficial to detect such complications early to decrease the frequency of emergency surgeries, which will help reduce mortality.

T-Cell receptor repertoire and genomic analysis of tracheal adenoid cystic carcinoma.

e18576 Background: Tracheal adenoid cystic carcinoma (TACC) is the second type of cancer in bronchial tumors, has a high rate of postoperative recurrence and poor prognosis for which therapeutic targets are unavailable. Currently, studies were mostly about ACC of salivary gland. Our study is aim to elucidate genomic landscape and predict clinical biomarker of TACC. Methods: We performed whole-exome sequencing (WES), T cell repertoire sequencing (TCR) and immunohistochemistry (IHC) on tumor tissue samples and matched peripheral blood (PB) samples from TACC patients. All patients were followed up for their disease-free survival. Results: 13 cases were enrolled from 2010 to 2019. Median age of 13 TACCs was 35 yrs. 7 patients were female. 12 patients were stage I. In 8 WES samples, TCEB3CL (62%, 5/8), LPAR3 (50%, 4/8), ALPI (38%, 3/8), ARID1A (38%, 3/8) and BCOR (38%, 3/8) mutated most frequently. The median TMB was 3.67 (1.37-6.77) mutations/Mb. 1 patient showed microsatellite instability high (MSI-H). 2 patients with the highest TMB both had POLE mutations. We compared frequency of most mutated genes in our 8 samples with three different ACC types, including 935 ACC of salivary gland cancer, 76 ACC of the lung, and 38 ACC of breast cancer. 7 mutated frequently genes were found both in TACC and other types of ACCs, including ARID1A, BCOR, ARID1B, KMT2C, KMT2D, CREBBP and FAT3. 6 of them were more frequent in TACC. 7 FFPE tumors and 13 PB samples from 13 TACCs were used to investigate immune microenvironment. In 13 PB samples, TCR diversity (shannon index) and clonality was negatively associated with age (Pearson, r = -0.53, p = 0.06; r = 0.53, p = 0.06, respectively). There was no significant association between the other clinical characteristics (gender and smoking history) and any TCR parameter (clonality, clonotype, shannon index). Patients with lower clonotype number had longer DFS than those with higher clonotype number (15.0 vs 9.5 months, p &lt; 0.001, 95% CI, 0.23-675.66, HR, 12.46), while shannon index and clonality was not significantly associated with DFS. Conclusions: The genetic mutations associated with TACC are different from those implicated in non-small cell lung cancer. TCR analysis as a useful of indicator of disease development and prognosis in TACC may be utilized to direct further immunotherapy.

Analysis of the clinical efficacy of liver resection combined with adjuvant microwave coagulation for patients with hepatocellular carcinoma.

BackgroundLiver resection has been widely applied as a curative measure in the treatment of hepatocellular carcinoma (HCC) patients. However, the high rate of postoperative recurrence observed following liver resection proposes a problem, the solution for which is yet to be well established. Microwave coagulation is a therapy that was recently proposed as an adjuvant tool. In this study, we intended to evaluate the effectiveness of microwave coagulation as an auxiliary therapeutic method for patients undergoing liver resection.MethodsA total of 236 consecutive patients classified as Barcelona Clinic Liver Cancer (BCLC) stage A who had only one tumor were enrolled in this retrospective study, regardless of tumor size. Survival analyses were performed using the Kaplan-Meier method, and the statistical differences between patients who underwent liver resection with and without adjuvant microwave coagulation were examined by the log-rank test. To investigate the prognostic factors for OS, we carried out univariate and multivariate Cox regression analyses.ResultsBased on the Kaplan-Meier curves, patients who underwent surgical resection with intraoperative adjuvant microwave coagulator had prolonged recurrence-free survival time and showed better overall survival (OS) than those who underwent surgical resection alone, with OS at 1, 3, and 5 years of 77.8%, 33.2%, 12.6% vs. 58.2%, 15.5%, 9.7%, respectively (log-rank P<0.001). The univariate and multivariate analyses demonstrated that tumor size, albumin, bilirubin, Child-Pugh score, and treatment method had significant prognostic power for both PFS and OS. According to the subgroup analyses based on the tumor size, there were significant differences in PFS and OS among overall subsets between the liver resection with adjuvant microwave coagulator and liver resection only groups.ConclusionsLiver resection combined with intraoperative adjuvant microwave coagulation had a better prognostic performance than treatment with liver resection alone. Adjuvant microwave coagulation should be suggested as an alternative treatment modality for BCLC stage A patients with a single tumor, regardless of its size.

Optimal Treatment for Tenosynovial Giant Cell Tumor of the Hand.

This review examines the following aspects of tenosynovial giant cell tumors (TSGCTs): the use of multiple names, the complex relationship between tumor growth pattern and location, the high rate of postoperative recurrence, local invasiveness, use of nonsurgical therapy with molecularly targeted drugs, and best current treatments. This tumor has been referred to by various names, but is now most frequently referred to as TSGCT. TSGCT is classified as localized and diffuse, in accordance with its growth characteristics. Most TSGCTs of the fingers are localized. TSGCT is likely a neoplastic process arising from synovial lining cells, in which tumor cells express the colony stimulating factor 1 (CSF1) gene. The postoperative recurrence rate of TSGCT is approximately 15%. The intrinsic characteristics of recurrence are not clear, and complete resection of the lesion is still the treatment mainstay. Moreover, TSGCT commonly grows out of a pseudocapsule. Therefore, to perform complete resection of TSGCT, surgery must be performed cautiously after appropriate preparation, by using anesthesia, a tourniquet, surgical loupe, and surgical microscopy. After accurate preoperative diagnosis, meticulous planning by surgeons is necessary. The lesion should be resected along with approximately 1-mm of healthy tissue at the adhesion site. In addition, because satellite lesions might be present near the tumor, careful dissection and observation of the color of surrounding tissue are important. International clinical trials of CSF1 receptor inhibitors for TSGCT treatment are ongoing.

Advances in circular RNAs and their role in glioma (Review).

Glioma is the most common primary tumour of the central nervous system, and is associated with a high postoperative recurrence rate and resistance to chemotherapy. High-grade glioblastoma in particular has a very poor prognosis and poses a serious threat to human health. Related studies have confirmed that the occurrence and development of gliomas are closely associated with the abnormal expression and regulation of genes. Moreover, the number of studies on the association of the expression of non-coding RNAs [linear RNAs, microRNAs and circular RNAs (circRNAs)] in human cells with glioma has been gradually increasing in recent years. Among those, circRNAs, previously considered to be 'splicing errors', have been shown to be highly expressed in eukaryotic cells and regulate the biological behaviour of gliomas. circRNAs are highly abundant and stable, and have become a research hotspot in the field of glioma molecular biology. The aim of the present review was to focus on the research progress regarding the association between circRNA expression and gliomas, and to provide a theoretical basis according to the currently available literature for further exploring this association. The present study may be of value for the early diagnosis, pathological grading, targeted therapy and prognostic evaluation of gliomas.

A new method for purifying Brazilin from lignum sappan – Cytotoxic and anti-proliferative effects in cell lines and improved survival in mice bearing urinary bladder carcinoma

Background: Urinary bladder carcinoma is characterized by high post-operative recurrence rates. Sufu'ning lotion, prepared with Lignum Sappan, can reduce the recurrence of urinary bladder carcinoma. Objectives: The present study describes a methodology for extracting and obtaining high purity brazilin from Lignum sappan and evaluates its effects on urinary bladder carcinoma, in vitro and in vivo . Materials and Methods: The brazilin was extracted from Lignum sappan, purified and identified. The purified brazilin was assessed in vitro for its effects on tumor cell viability and growth using human (T24) and mouse urinary bladder (BTT) cancer cell lines. The role of brazilin in the inhibition of the cell cycle was determined by flow cytometry. The in vivo activity of brazilin was assessed based on the survival of tumor-bearing mice. Results: Brazilin was purified of 99.10% purity and was bioactive as it significantly (P

Establishment of a Genomic-Clinicopathologic Nomogram for Predicting Early Recurrence of Hepatocellular Carcinoma After R0 Resection

BackgroundA high rate of postoperative recurrence, especially early recurrence (ER) occurring within 1 year, seriously impedes patients with hepatocellular carcinoma (HCC) from achieving long-term survival. This study aimed to establish a genomic-clinicopathologic nomogram for precisely predicting ER in HCC patients after R0 resection. MethodsTwo reliable datasets from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) databases were selected as the training and validation cohorts, respectively. The prognostic genes related to ER were screened out by univariate Cox regression analysis and differential expression analysis. The gene-based prognostic index was constructed using LASSO and Cox regression analyses, and its independent prognostic value was assessed by Kaplan-Meier and multivariate Cox analyses. Gene set enrichment analysis (GSEA) was performed to explore the biological pathways related to the prognostic index. Finally, the nomogram integrating all the independent prognostic factors was established and comprehensively evaluated by calibration plots, the C-index, receiver operating characteristic curves, and decision curve analysis. ResultsNine dysregulated and prognostic genes related to ER (ZNF131, TATDN2, TXN, DDX55, KPNA2, ZNF30, TIMELESS, SFRP1, and COLEC11) were identified (all P < 0.05). The prognostic index model based on the 9 genes was successfully constructed using the TCGA cohort and showed a certain capability to discriminate the ER group from the non-ER group (P < 0.05) and good independent prognostic value in terms of predicting poor early recurrence-free survival (P < 0.05). Eight biological pathways significantly related to ER were identified by GSEA, such as “cell cycle”, “homologous recombination” and “p53 signaling pathway.” The genomic-clinicopathologic nomogram integrating the 9-gene-based prognostic index and TNM stage displayed significantly higher predictive accuracy and clinical application value than that of TNM stage model both in the training and validation cohorts (all P < 0.05). ConclusionsThe novel genomic-clinicopathologic nomogram may be a convenient and powerful tool for accurately predicting ER in HCC patients after R0 resection.

Support System of Cystoscopic Diagnosis for Bladder Cancer Based on Artificial Intelligence.

Introduction: Nonmuscle-invasive bladder cancer has a relatively high postoperative recurrence rate despite the implementation of conventional treatment methods. Cystoscopy is essential for diagnosing and monitoring bladder cancer, but lesions are overlooked while using white-light imaging. Using cystoscopy, tumors with a small diameter; flat tumors, such as carcinoma in situ; and the extent of flat lesions associated with the elevated lesions are difficult to identify. In addition, the accuracy of diagnosis and treatment using cystoscopy varies according to the skill and experience of physicians. Therefore, to improve the quality of bladder cancer diagnosis, we aimed to support the cystoscopic diagnosis of bladder cancer using artificial intelligence (AI).Materials and Methods: A total of 2102 cystoscopic images, consisting of 1671 images of normal tissue and 431 images of tumor lesions, were used to create a dataset with an 8:2 ratio of training and test images. We constructed a tumor classifier based on a convolutional neural network (CNN). The performance of the trained classifier was evaluated using test data. True-positive rate and false-positive rate were plotted when the threshold was changed as the receiver operating characteristic (ROC) curve.Results: In the test data (tumor image: 87, normal image: 335), 78 images were true positive, 315 true negative, 20 false positive, and 9 false negative. The area under the ROC curve was 0.98, with a maximum Youden index of 0.837, sensitivity of 89.7%, and specificity of 94.0%.Conclusion: By objectively evaluating the cystoscopic image with CNN, it was possible to classify the image, including tumor lesions and normality. The objective evaluation of cystoscopic images using AI is expected to contribute to improvement in the accuracy of the diagnosis and treatment of bladder cancer.

TRIP6 promotes tumorigenic capability through regulating FOXC1 in hepatocellular carcinoma

BackgroundHepatocellular carcinoma (HCC) is an aggressive malignant tumor with poor prognosis that is characterized by high rates of postoperative recurrence and mortality. Understanding the molecular mechanism of this malignancy is of great significance for the development of new and effective strategies for the treatment of hepatocellular carcinoma. Thyroid hormone receptor-interacting protein 6 (TRIP6), also known as zyxin-related protein-1 or ZRP-1, is an adaptor protein that belongs to the zyxin family of LIM proteins. Recent studies showed that TRIP6 is involved in carcinogenesis. But the functional role of TRIP6 in HCC has not been reported to date. Methods: TRIP6 expression level in HCC cell lines and normal cell line was measured by qPCR. The roles of TRIP6 on HCC cell proliferation, colony formation, and invasion were examined by MTT assay, colony formation assay, and transwell invasion assay, respectively. The effect of TRIP6 on the overall survival of HCC patients was further analyzed. ChIP assay and western blot were performed to validate whether FOXC1 was involved in the regulation of TRIP6 expression. ResultsWestern blot and immunohistochemical analyses showed that TRIP6 expression was up-regulated in HCC tissues compared with adjacent non-tumor tissues. Kaplan-Meier survival analysis indicated that upregulation of TRIP6 was dramatically associated with poor overall survival. TRIP6 knockdown significantly inhibited cell migration, invasion, and proliferation, and its effect on cell proliferation was mediated by the modulation of cell cycle progression. FOXC1 also played a vital role in TRIP6 regulation. TRIP6 mediated the FOXC1-regulated proliferation, invasion, and migration in vitro and tumor growth in vivo. ConclusionsThese results suggest that TRIP6 may contribute to the invasiveness and metastasis of HCC cells, and provide new insight into the crucial role of TRIP6 in tumorigenesis and cancer progression.