Prognostic Value of Alpha-Fetoprotein in Unresectable Hepatocellular Carcinoma Treated with Hepatic Artery Infusion Chemotherapy Combined with Lenvatinib and Camrelizumab.

Purpose: This study aimed to assess the prognostic significance of alpha-fetoprotein (AFP) response in patients with unresectable hepatocellular carcinoma (u-HCC) who underwent hepatic artery infusion chemotherapy (HAIC) combined with lenvatinib and camrelizumab. Methods: A retrospective review was conducted on patients with u-HCC receiving treatment with HAIC combined with lenvatinib and camrelizumab. Early AFP response was defined as a >20% decrease in AFP within 4 weeks, and AFP response as a >75% decrease in AFP within 8 weeks. The correlation between early AFP response, AFP response, therapeutic response, overall survival (OS), and progression-free survival (PFS) was investigated. Results: The study included 63 patients. AFP responders exhibited superior objective response rates compared to AFP non-responders, as determined by RECIST v1.1 or mRECIST criteria (45.5 vs. 18.2%, p=0.014, or 81.8 vs. 48.5%, p=0.013). Furthermore, early AFP responders demonstrated prolonged OS (not reached vs. 8.0 months, p<0.001) and PFS (13.3 vs. 3.0 months, p= 0.018) relative to early AFP non-responders. Similarly, AFP responders exhibited improved OS (not reached vs. 9.0 months, p<0.001) and PFS (19.3 vs. 5.1 months, p=0.002) compared to AFP non-responders. Multivariate analysis results indicated that both early AFP response and AFP response independently predicted OS [hazard ratio (HR) 2.963, 95% confidence interval (CI) 1.333-6.585, p=0.008, and HR 6.182, 95% CI 1.780-21.466, p=0.004] and PFS (HR 2.186, 95% CI 1.107-4.318, p=0.024, and HR 3.078, 95% CI 1.407-6.730, p=0.005), serving as significant prognostic values. Conclusion: Early AFP response and AFP response serve as predictive biomarkers for the effectiveness of HAIC combined with lenvatinib and camrelizumab in patients with u-HCC.

AURKB targets DHX9 to promote hepatocellular carcinoma progression via PI3K/AKT/mTOR pathway.

Aurora kinase B (AURKB) is known to play a carcinogenic role in a variety of cancers, but its underlying mechanism in liver cancer is unknown. This study aimed to investigate the role of AURKB in hepatocellular carcinoma (HCC) and its underlying molecular mechanism. Bioinformatics analysis revealed that AURKB was significantly overexpressed in HCC tissues and cell lines, and its high expression was associated with a poorer prognosis in HCC patients. Furthermore, downregulation of AURKB inhibited HCC cell proliferation, migration, and invasion, induced apoptosis, and caused cell cycle arrest. Moreover, AURKB downregulation also inhibited lung metastasis of HCC. AURKB interacted with DExH-Box helicase 9 (DHX9) and targeted its expression in HCC cells. Rescue experiments further demonstrated that AURKB targeting DHX9 promoted HCC progression through the PI3K/AKT/mTOR pathway. Our results suggest that AURKB is significantly highly expressed in HCC and correlates with patient prognosis. Targeting DHX9 with AURKB promotes HCC progression via the PI3K/AKT/mTOR pathway.

Beneficial effects of maintaining liver function during hepatic arterial infusion chemotherapy combined with tyrosine kinase and programmed cell death protein-1 inhibitors on the outcomes of patients with unresectable hepatocellular carcinoma.

BACKGROUND AND AIM: Combination therapy is the primary treatment for unresectable hepatocellular carcinoma (u-HCC). The hepatic functional reserve is also critical in the treatment of HCC. In this study, u-HCC was treated with combined hepatic arterial infusion chemotherapy (HAIC), tyrosine kinase inhibitors (TKIs), and programmed cell death protein-1 (PD-1) inhibitors to analyze the therapeutic response, progression-free survival (PFS), and safety. METHODS: One hundred sixty-two (162) patients with u-HCC were treated by combination therapy of HAIC, TKIs, and PD-1 inhibitors. PFS was assessed by Child-Pugh (CP) classification subgroups and the change in the CP score during treatment. RESULTS: The median PFS was 11.7 and 5.1 months for patients with CP class A (CPA) and CP class B (CPB), respectively (p = 0.013), with respective objective response rates of 61.1 and 27.8% (p = 0.002) and conversion rates of 16 and 0% (p = 0.078). During treatment, the CP scores in patients with CPA worsened less in those with complete and partial response than in those with stable and progressive disease. In the CP score 5, patients with an unchanged CP score had longer PFS than those with a worsened score (Not reached vs. 7.9 months, p = 0.018). CPB was an independent factor negatively affecting treatment response and PFS. Patients with CPA responded better to the combination therapy and had fewer adverse events (AEs) than those with CPB. CONCLUSIONS: Thus, triple therapy is more beneficial in patients with good liver function, and it is crucial to maintain liver function during treatment.

Development and validation of nomograms to evaluate the survival outcome of HCC patients undergoing selective postoperative adjuvant TACE.

PURPOSE: The objective of this study was to develop and validate a novel prognostic nomogram to evaluate the survival benefit of hepatocellular carcinoma (HCC) patients receiving postoperative adjuvant transarterial chemoembolization (PA-TACE). MATERIALS AND METHODS: Clinical data of HCC patients who underwent hepatectomy at four medical centers were retrospectively analyzed, including those who received PA-TACE and those who did not. These two categories of patients were randomly allocated to the development and validation cohorts in a 7:3 ratio. RESULTS: A total of 1505 HCC patients who underwent hepatectomy were included in this study, comprising 723 patients who did not receive PA-TACE and 782 patients who received PA-TACE. Among them, patients who received PA-TACE experienced more adverse events, although these events were mild and manageable (Grade 1-2, all p < 0.05). Nomograms were constructed and validated for patients with and without PA-TACE using independent predictors that influenced disease-free survival (DFS) and overall survival (OS). These two nomograms had C-indices greater than 0.800 in the development cohort and exhibited good calibration and discrimination ability compared to six conventional HCC staging systems. Patients in the intermediate-to-high-risk group in the nomogram who received PA-TACE had higher DFS and OS (all p < 0.05). In addition, tumor recurrence was significantly controlled in the intermediate-to-high-risk group of patients who received PA-TACE, while there was no significant difference in the low-risk group of patients who received PA-TACE. CONCLUSION: The nomograms were developed and validated based on large-scale clinical data and can serve as online decision-making tools to predict survival benefits from PA-TACE in different subgroups of patients.

Comprehensive Analysis of circRNA, lncRNA, miRNA and mRNA Expression Profiles and Their Competing Endogenous RNA Networks in Hepatitis B Virus-Related Hepatocellular Carcinoma.

Pursuing knowledge about circular RNA (circRNA), long non-coding RNA (lncRNA), microRNA (miRNA), and messenger RNA (mRNA) expression profiles and their competing endogenous RNA (ceRNA) networks in hepatitis B virus-related hepatocellular carcinoma (HBV-related HCC) was the focus of this research. Expression patterns of circRNAs, lncRNAs, miRNAs, and mRNAs were searched for in relation to HBV-related HCC using whole-transcriptome sequencing. The expression levels of chosen circRNA, lncRNA, miRNA, and mRNA were analyzed using quantitative reverse transcription-polymerase chain reaction (qRT-PCR). The potential connections and roles of ceRNA were deduced via bioinformatics research. The sum of 284 circRNAs, 2,927 lncRNAs, 693 miRNAs, and 5566 mRNAs were discovered to be expressed at considerably different levels in HBV-related HCC tissue and adjacent normal tissue. And the most significantly up- and down-regulated circRNAs, lncRNAs, miRNAs, and mRNAs were verified in HBV-related HCC by qRT-PCR. The circRNA/miRNA/mRNA and lncRNA/miRNA/mRNA networks of HBV-related HCC were established, and the ceRNA regulatory networks revealed the gene expression mechanisms controlled by ncRNAs. Collectively, we revealed the contribution of various circRNA, lncRNA, miRNA, and mRNA expression profiles and identified their ceRNA regulatory networks in HBV-related HCC, providing a theoretical basis for further exploration.

Development and Validation of a Nomogram for Predicting Postoperative Early Relapse and Survival in Hepatocellular Carcinoma.

BACKGROUND: Early relapse after hepatectomy presents a significant challenge in the treatment of hepatocellular carcinoma (HCC). The aim of this study was to construct and validate a novel nomogram model for predicting early relapse and survival after hepatectomy for HCC. PATIENTS AND METHODS: We conducted a large-scale, multicenter retrospective analysis of 1,505 patients with surgically treated HCC from 4 medical centers. All patients were randomly divided into either the training cohort (n=1,053) or the validation cohort (n=452) in a 7:3 ratio. A machine learning-based nomogram model for prediction of HCC was established by integrating multiple risk factors that influence early relapse and survival, which were identified from preoperative clinical data and postoperative pathologic characteristics of the patients. RESULTS: The median time to early relapse was 7 months, whereas the median time from early relapse to death was only 19 months. The concordance indexes of the postoperative nomogram for predicting disease-free survival and overall survival were 0.741 and 0.739, respectively, with well-calibrated curves demonstrating good consistency between predicted and observed outcomes. Moreover, the accuracy and predictive performance of the postoperative nomograms were significantly superior to those of the preoperative nomogram and the other 7 HCC staging systems. The patients in the intermediate- and high-risk groups of the model had significantly higher probabilities of early and critical recurrence (P<.001), whereas those in the low-risk group had higher probabilities of late and local recurrence (P<.001). CONCLUSIONS: This postoperative nomogram model can better predict early recurrence and survival and can serve as a useful tool to guide clinical treatment decisions for patients with HCC.

Pretreatment Neutrophil-to-Lymphocyte Ratio as Prognostic Biomarkers in Patients with Unresectable Hepatocellular Carcinoma Treated with Hepatic Arterial Infusion Chemotherapy Combined with Lenvatinib and Camrelizumab.

Purpose: This study aimed to assess the prognostic significance of the neutrophil-lymphocyte ratio (NLR) in patients with unresectable hepatocellular carcinoma (u-HCC) treated with hepatic artery infusion chemotherapy (HAIC) combined with lenvatinib and camrelizumab. Patients and Methods: We conducted a retrospective cohort study involving patients diagnosed with u-HCC who underwent HAIC combined with lenvatinib and camrelizumab. Patients were stratified into two cohorts using the median NLR as the cutoff point. We then assessed treatment response, overall survival (OS), progression-free survival (PFS), and adverse events in these patient groups. Results: Between October 2020 and April 2022, a total of 88 patients were enrolled in the study. The overall cohort exhibited a median PFS of 7.9 months, while the median OS was not reached, and a median NLR of 3.46. Notably, the group with NLR<3.46 demonstrated significantly superior OS (not reached vs 9.6 months, p = 0.017) and PFS (18.3 vs 5.3 months, p = 0.0015) compared to the NLR≥3.46 group. Furthermore, multivariate analysis revealed that an alpha-fetoprotein (AFP) ≥ 400 ng/mL [hazard ratio (HR), 2.133; 95% confidence interval (CI), 1.102-4.126; p = 0.024], Barcelona Clinical Hepatocellular Carcinoma (BCLC) stage C (HR, 2.319; 95% CI, 1.128-4.764; p = 0.022), and NLR ≥3.46 (HR, 2.35; 95% CI, 1.239-4.494; p = 0.009) were identified as independent risk factors for OS. Additionally, multivariate analysis demonstrated that AFP ≥ 400 ng/mL, BCLC stage C, and NLR ≥ 3.46 were independent negative factors of PFS. Conclusion: NLR can be associated with outcomes in patients with u-HCC treated with HAIC combined with lenvatinib and camrelizumab.

Postoperative adjuvant transarterial chemoembolisation improves survival of hepatocellular carcinoma patients with microvascular invasion: A multicenter retrospective cohort.

BACKGROUND: We aimed to investigate the efficacy of postoperative adjuvant transarterial chemoembolisation (PA-TACE) in patients with hepatocellular carcinoma (HCC) complicated by microvascular invasion (MVI). METHODS: A retrospective analysis of 1505 patients with HCC who underwent hepatectomy at four medical centers, including 782 patients who received PA-TACE and 723 patients who did not receive adjuvant PA-TACE, has been conducted. Propensity score matching (PSM) (1:1) was performed on the data to minimise selection bias, which resulted in a balanced clinical profile between groups. RESULTS: After PSM, 620 patients who received PA-TACE and 620 patients who did not receive PA-TACE were included. Disease-free survival (DFS, 1-, 2-, and 3-year: 88%-68%-61% vs. 70%-58%-51%, p < 0.001) and overall survival (OS, 1-, 2-, and 3-year: 96%-89%-82% vs. 89%-77%-67%, p < 0.001) were significantly higher in patients who received PA-TACE than in those who did not. Patients with MVI who received PA-TACE had significantly higher DFS (1-, 2-, and 3-year: 68%-57%-48% vs. 46%-31%-27%, p < 0.001) and OS (1-, 2-, and 3-year: 96%-84%-77% vs. 79%-58%-40%, p < 0.001) than those who did not receive PA-TACE. Among the six different liver cancer stages, MVI-negative patients did not have significant survival outcomes from PA-TACE (p > 0.05), whereas MVI-positive patients achieved higher DFS and OS from it (p < 0.05). Liver dysfunction, fever, and nausea/vomiting were the most common adverse events in patients receiving PA-TACE. There was no significant difference in grade 3 or 4 adverse events between the groups (p > 0.05). CONCLUSIONS: Postoperative adjuvant transarterial chemoembolisation has a good safety profile and may be a potentially beneficial treatment modality for survival outcomes in patients with HCC, especially those with concomitant MVI.

Rare benign liver tumors that require differentiation from hepatocellular carcinoma: focus on diagnosis and treatment.

BACKGROUND/AIM: Recently, an increase in the number of asymptomatic rare benign liver tumors (BLTs) has been reported during health check-ups. It is difficult to determine the nature of partial rare BLTs and not easy to distinguish from malignant liver tumors. This study aimed to analysis clinical features, diagnosis and treatment of rare BLTs to reduce misdiagnosis and provide reference for clinical practice. METHODS: From January 2012 to January 2021, we treated 112 rare BLTs by hepatectomy, including 54 focal nodular hyperplasias, 14 hepatocellular adenomas, 28 hepatic angiomyolipomas, 3 hepatic granulomas, 2 inflammatory pseudotumors of the liver, 2 nodular regenerative hyperplasia, 2 hepatic lipomas, 1 solitary fibrous tumor of the liver, 1 hepatic schwannoma and 1 hepatic myelolipoma. RESULTS: The majority of patients were middle-aged female and asymptomatic. Single tumors were dominant. The diagnostic accuracies of computed tomography (CT) and magnetic resonance imaging (MRI) were 32.5% and 44.2%, respectively. The majority of tumors were likely to be misdiagnosed as hepatocellular carcinoma (HCC) or difficult to distinguish from HCC. All patients underwent surgical treatment. Postoperative pathological and immunohistochemical examination can confirm the diagnosis. No patients without tumor recurrence or metastasis during follow-up period. CONCLUSION: Altogether, the clinical symptoms of rare BLTs lack specificity, and their preoperative diagnosis largely depends on imaging examination, with a low diagnostic accuracy rate and high chances of misdiagnosis as HCC. Diagnosis is confirmed by pathological and immunohistochemical examination. Surgical resection for rare BLT is safe and effective, regular postoperative follow-up is necessary.

Hepatectomy After Conversion Therapy for Initially Unresectable HCC: What is the Difference?

Purpose: Conversion therapy gives some patients with initially unresectable hepatocellular carcinoma (HCC) access to surgery. The purpose of this study was to evaluate the safety and efficacy of hepatectomy after conversion therapy and how it differed from those who undergoing direct hepatectomy. Patients and Methods: From January 2018 to April 2022, 745 patients underwent hepatectomy for HCC were enrolled. Among them, 41 patients of unresectable HCC underwent hepatectomy after conversion therapy. A demographically and clinically comparable cohort was created from the remaining patients in a 1:1 ratio using propensity score matching. Results: The median duration of conversion therapy was 108 (42-298) days, 8 patients achieved complete response (CR) and 33 achieved partial response (PR). Conversion therapy resulted in some degree of myelosuppression, but liver function index remained good. Compared with the direct hepatectomy group, the conversion group had more blood loss (600 mL vs 400 mL, p=0.015), longer operative time (270 min vs 240 min, p=0.02), higher blood transfusion rates, and longer hospital stay (8 days vs 11 days, p<0.001). Patients in the conversion group had significantly more complications of any grade (82.9% vs 51.2%, p=0.002) and grade 3/4 (26.8% vs 4.9%, p=0.013), and 6 patients developed post-hepatectomy liver failure (PHLF). There were no deaths in either group. All patients achieved R0 resection, 6 (6/41, 14.6%) achieved pathological complete response (pCR), 14 achieved major pathologic responses (MPR). During a median follow-up of 12.8 months, 14 patients in the conversion group experienced recurrence or metastasis, no deaths. Conclusion: Hepatectomy after conversion therapy was more difficult than direct hepatectomy, but accurate preoperative assessment could ensure the safety of the surgery. The damage of liver function after conversion therapy was more severe than expected, PHLF should be prevented and treated. Hepatectomy was effective and necessary, postoperative pathological examination could provide guidance for adjuvant therapy.

Hepatic arterial infusion chemotherapy combined with PD-1 inhibitors and tyrosine kinase inhibitors for unresectable hepatocellular carcinoma: A tertiary medical center experience.

Background: Unresectable hepatocellular carcinoma (u-HCC) still accounts for the majority of newly diagnosed HCC which with poor prognosis. In the era of systemic therapy, combination therapy with programmed cell death protein-1 (PD-1) inhibitors and tyrosine kinase inhibitors (TKIs) has become mainstream. Hepatic arterial infusion chemotherapy (HAIC) as a local treatment has also shown a strong anti-tumor effect. This study aimed to investigate the efficacy and safety of HAIC, PD-1 inhibitors plus TKIs for u-HCC. Methods: This retrospective study included patients with initially u-HCC between October 2020 to April 2022 who had received at least one cycle of therapy with HAIC, PD-1 inhibitors plus TKIs. The primary outcome included overall response rate (ORR), the disease control rate (DCR), surgical conversion rate, progression-free survival (PFS) and treatment-related adverse events. Results: A total of 145 patients were included in the study. The median treatment cycle of HAIC and PD-1 inhibitors were 3 and 4, respectively. According to the modified RECIST criteria, the best ORR was 57.2% (83/145), 9 had achieved complete response (CR), DCR was 89.7% (130/145). Median time to achieve CR or PR was 65 days. Surgical conversion rate was 18.6% (27/145), seven patients (7/27,25.9%) achieved pathological complete response (pCR). The median follow-up was 12.5 months (4.5-20 months), and the median PFS was 9.7 months. Subgroup analysis showed that Child-pugh A patients had higher DCR (92.2% vs 79.3%, p=0.041) than Child-pugh B patients, as well as increased successful conversion rate (22.4% vs 3.4%, p=0.019). Patients without vascular invasion and extrahepatic metastases showed higher PR (63.4% vs 43.3%, p<0.05) and ORR (73.2% vs 50.0%, p<0.05) than those with vascular invasion. The ORR (73.2% vs 45.5%, p<0.05) and DCR (95.1% vs 78.8%, p<0.05) were also significantly better than those of patients with extrahepatic metastases. HAIC regimen was not related to efficacy (All p>0.05). The incidence rate of grade 3/4 treatment-related AEs was 17.7% without fatal events. Conclusion: The triple combination therapy of HAIC and PD-1 inhibitors plus TKIs for patients with initially unresectable HCC exhibited satisfactory efficacy with tolerable toxicity.

Combined identification of three lncRNAs in serum as effective diagnostic and prognostic biomarkers for hepatitis B virus-related hepatocellular carcinoma.

Hepatitis B virus-related hepatocellular carcinoma (HBV-related HCC) is a common, highly invasive malignant tumor associated with a high mortality rate. This study aimed to identify the effective diagnostic and prognostic biomarkers for HBV-related HCC. With HBV-related HCC RNA-sequencing data of The Cancer Genome Atlas (TCGA) database, 159 differentially expressed long noncoding RNAs (lncRNAs) between HBV-related HCC and para-carcinoma normal samples were identified, and 12 lncRNAs were eventually assessed for deeper research. Classification analysis developed a three-lncRNA signature of AC005332.5, ELF3-AS1 and LINC00665, which was demonstrated to be the most discriminatory with an AUC (Area under the curve) value of 0.913 (95% CI: 0.8610-0.9665) and verified in validation patients. The expression levels of AC005332.5, ELF3-AS1 and LINC00665 were significantly changed with different tumor stages or grades. Survival analysis revealed that AC005332.5, ELF3-AS1 and LINC00665 were highly associated with the prognosis of overall survival. Additionally, the lncRNA signature yielded statistical significance to predict clinical outcomes independently from other clinical variables in validation patients, as suggested in the multivariate Cox hazards analysis. Conclusively, a three-lncRNA signature of AC005332.5, ELF3-AS1 and LINC00665 may serve as an excellent diagnostic biomarker for HBV-related HCC and potential prognostic significance for HBV-related HCC sufferers.

The Emerging Roles of Circ-ABCB10 in Cancer.

Circular RNAs (circRNAs) are non-coding RNAs (ncRNAs) without 5' caps and 3' tails, which are formed from precursor mRNAs (pre-mRNAs) that are inversely back-spliced by exons. CircRNAs are characterized by a covalently closed circular structure and are abundantly expressed in eukaryotic cells. With the development of RNA-sequencing, it was discovered that circRNAs play important roles in the regulation of numerous human genes and are related to the occurrence, development, and prognosis of diseases. Studies in various cancers have revealed that circRNAs have both positive and negative effects on the occurrence and development of tumors. Circ-ABCB10, a circular RNA originating from exons of ABCB10 located on chromosome 1q42, has been proven to play an important role in different types of cancers. Here, we report the primary findings of recent research studies by many contributors about the roles of circ-ABCB10 in cancer and clearly formulate its influence and functions in different aspects of cancer biology, which gives us a broad picture of circ-ABCB10. Thus, this study aimed to generalize the roles of circ-ABCB10 in the diagnosis and treatment of different types of tumors and its related miRNA genes. In this way, we wish to provide a sufficient understanding and assess the future development direction of the research on circ-ABCB10.

Identification of a Novel Survival-Related circRNA-miRNA-mRNA Regulatory Network Related to Immune Infiltration in Liver Hepatocellular Carcinoma.

Increasing studies have reported that circular RNAs (circRNAs) play critical roles in tumorigenesis and cancer progression. However, the underlying regulatory mechanisms of circRNA-related competing endogenous RNA (ceRNA) in liver hepatocellular carcinoma (LIHC) are still unclear. In the present study, we discovered dysregulated circRNAs through Gene Expression Omnibus (GEO) analysis and validated the expression of the top seven circRNAs with upregulated expression by qRT-PCR and Sanger sequencing. Then, the Cancer-Specific CircRNA Database (CSCD) was used to predict the downstream miRNAs of seven circRNAs, and expression and survival analyses through The Cancer Genome Atlas (TCGA) were performed to identify the key miRNA in LIHC. Thereafter, the hsa_circ_0017264-hsa-miR-195-5p subnetwork was successfully constructed. Subsequently, we predicted downstream target genes of hsa-miR-195-5p with TargetScan, miRDB, and mirtarbase and overlapped them with differentially expressed mRNAs to obtain 21 target genes. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed to predict the biological and functional roles of these target genes. Finally, with Pearson correlation and prognostic value analysis, a survival-related hsa_circ_0017264-hsa-miR-195-5p-CHEK1/CDC25A/FOXK1 axis was established. Gene set enrichment analysis (GSEA) was performed to determine the function of CHEK1/CDC25A/FOXK1 in the ceRNA network. Moreover, immune infiltration analysis revealed that the ceRNA network was markedly associated with the levels of multiple immune cell infiltrates, immune cell biomarkers and immune checkpoints. Overall, the hsa_circ_0017264-hsa-miR-195-5p-CHEK1/CDC25A/FOXK1 network might provide novel insights into the potential mechanisms underlying LIHC onset and progression.

Targeting Notch4 in Cancer: Molecular Mechanisms and Therapeutic Perspectives.

The dysregulation of Notch signaling is found in many cancers and is closely related to cancer progression. As an important Notch receptor, abnormal Notch4 expression affects several tumor-cell behaviors, including stemness, the epithelial-mesenchymal transition, radio/chemoresistance and angiogenesis. In order to inhibit the oncogenic effects of Notch4 activation, several methods for targeting Notch4 signaling have been proposed. In this review, we summarize the known molecular mechanisms through which Notch4 affects cancer progression. Finally, we discuss potential Notch4-targeting therapeutic strategies as a reference for future research.

The Roles of circMTO1 in Cancer.

Circular RNAs (circRNAs) are a recently discovered type of covalently-closed circular non-coding RNAs, mainly formed by non-sequential back-splicing of precursor mRNAs (pre-mRNAs). Recent studies have demonstrated that circRNAs can have either oncogenic or tumor-suppressor roles depending on the cellular context. CircRNA mitochondrial tRNA translation optimization 1 (circMTO1), a recently reported circular RNA originating from exons of MTO1 located on chromosome 6q13, was proved to be abnormally expressed in many malignant tumors, such as hepatocellular carcinoma, gastric carcinoma and colorectal cancer, resulting in tumor initiation and progression. However, there are no reviews focusing on the roles of circMTO1 in cancer. Here, we first summarize the main biological characteristics of circMTO1, and then focus on its biological functions and the possible underlying molecular mechanisms. Finally, we summarize the roles of circMTO1 in cancer and discuss future prospects in this area of research.

The oncogenic role of HBXIP.

Hepatitis B X-interacting protein (HBXIP) is a conserved protein of 19 kDa that was originally identified as a binding partner of hepatitis B virus X protein. Emerging evidence indicates that HBXIP is highly expressed in a variety of cancers and is correlated with poor clinical outcomes in cancer patients. HBXIP plays a critical role in cancer progression, but the underlying mechanisms are still unclear. In this review, we primarily focus on publications investigating HBXIP in cancer research, including its expression and clinical significance in cancer patients, its role as a coactivator of transcription factors in cancer cells, its inhibitory effects on the mitochondrial cytochrome c-caspase apoptotic pathway, as well as its roles in promoting mitosis and drug resistance in cancer cells, its regulatory effects on cancer metabolism, and its relationships with other signaling pathways or microRNAs in cancer. This review aims to compile and summarize existing knowledge of the functions of HBXIP in cancer, which provides a comprehensive reference for future studies on the oncogenic mechanisms of HBXIP.

The Emerging Picture of the Roles of CircRNA-CDR1as in Cancer.

Circular RNAs (circRNAs) are covalently closed circular structures without 5' caps and 3' tails, which are mainly formed from precursor mRNAs (pre-mRNAs) via back-splicing of exons. With the development of RNA sequencing and bioinformatic analysis, circRNAs were recently rediscovered and found to be widely expressed in the tree of life. Cerebellar degeneration-related protein 1 antisense RNA (CDR1as) is recognized as one of the most well-identified circRNAs. It contains over 70 miR-7 binding sites and can regulate gene activity by sponging miR-7. Increasing numbers of studies have recently demonstrated that CDR1as is abnormally expressed in many types of tumors, such as colorectal cancer, cholangiocarcinoma and osteosarcoma, and plays a vital role in the development of cancer. However, there are few reviews focusing on CDR1as and cancer. Hence, it is important to review and discuss the role of CDR1as in cancer. Here, we first review the main biological features of CDR1as. We then focus on the expression and roles of CDR1as in cancer. Finally, we summarize what is known on the role of CDR1as in cancer and discuss future prospects in this area of research.

Long-term oncological outcomes in robotic versus laparoscopic approach for rectal cancer: A systematic review and meta-analysis.

BACKGROUND: Short-term outcomes of robotic mesorectal excision for rectal cancer resection seem comparable to those of conventional laparoscopic mesorectal excision. However, the long-term oncological outcomes of robot mesorectal excision require further investigation. MATERIALS AND METHODS: The PubMed, EMBASE, Medline, and Cochrane Library databases were searched from the date of database inception to March 31, 2019 for all available trials; the results of robotic and laparoscopic mesorectal excision for rectal cancer surgery were compared. Survival parameters, including overall survival (OS) and disease-free survival (DFS), were independently extracted by two investigators. Hazard ratios (HRs) were calculated using random- or fixed-effects models. The presence of heterogeneity was assessed using Q test, and the extent of heterogeneity was quantified by I2 index. The meta-analysis was performed using Review Manager software, version 5.3. RESULTS: A total of seven studies including 2593 patients (1362 treated by robotic mesorectal excision and 1231 by laparoscopic mesorectal excision) were included. Pooled analyses showed no significant difference in OS (HR = 0.94, 95% confidence interval [CI]: 0.63 to 1.39, P = 0.75) or DFS (HR = 0.93, 95% CI: 0.79 to 1.10, P = 0.85) between the robotic and laparoscopic mesorectal excision for treatment of rectal cancer. CONCLUSION: Regarding long-term survival, robotic mesorectal excision for rectal cancer is comparable to laparoscopic mesorectal excision. More prospective, multicenter randomized trials with longer follow-up periods are needed to determine the long-term outcomes of patients undergoing robotic mesorectal excision.

The Prognostic Value of the MiR-200 Family in Colorectal Cancer: A Meta-analysis with 1882 Patients.

Background: MicroRNAs are small non-coding RNAs containing 18-22 nucleotides which play a role in RNA silencing and post-transcriptional regulation of their target genes. The MiR-200 family comprises miR-141, miR-200a, miR-200b, miR-200c and miR-429. Increasing evidence indicates that miR-200 microRNAs play a role in cancer metastasis. For example, miR-200 microRNAs were reported to influence the prognosis in colorectal cancer patients by regulating the expression of genes related to the epithelial-mesenchymal transition6. Previous studies have shown that the high expression of miR-200 microRNAs has an impact on the overall survival and Relapse-free Survival of CRC patients. However, the study results were inconsistent. Results: Data from a total of 1882 patients from 9 studies was included in the meta-analysis. Poorer Relapse-free Survival (RFS) was observed in patients with high expression levels of miR-200 microRNAs (HR=1.13, 95% CI 1.04-1.23). Additionally, subgroup analysis of sample types revealed a significant association between higher expression of the miR-200 family in the plasma and poorer OS (HR=1.23, 95% CI 1.08-1.41) and RFS (HR=2.39, 95% CI 1.20-4.77), which indicates that the miR-200 family can be used as an easily detectable biomarker for evaluation of the prognosis of patients with colorectal cancer. Conclusions: High expression levels of miR-200 microRNAs were associated with poor clinical outcomes in colorectal cancer patients. The miR-200 family can therefore potentially serve as a prognostic biomarker. Further studies should be performed to verify the clinical utility of the miR-200 family in colorectal cancer.