Renhua Wan

Purpose: HCC exhibits a high postoperative recurrence rate, with early recurrence (≤ 2 years) accounting for 70% of cases, predominantly associated with high-risk recurrence factors. Common adjuvant therapies for HCC include postoperative adjuvant hepatic arterial infusion chemotherapy (PA-HAIC) and postoperative adjuvant transarterial chemoembolization (PA-TACE). This study evaluates the comparative efficacy and safety of PA-HAIC versus PA-TACE in preventing early recurrence among HCC patients with postoperative high-risk recurrence factors. Patients and Methods: A retrospective analysis included 170 HCC patients with high-risk recurrence factors following surgical resection (2018– 2023), divided into PA-HAIC (n=23) and PA-TACE (n=147) groups. To mitigate potential biases and adjust for baseline characteristics, propensity score matching (PSM) was performed. Survival analyses for two primary endpoints, recurrence-free survival (RFS) and overall survival (OS), were then conducted using the Kaplan-Meier method and Cox proportional hazards regression. Adverse event (AE) rates and severity were compared. Results: Post-PSM analysis revealed significantly superior RFS rates in the PA-HAIC group versus PA-TACE at 6,12,and 24 months (100%, 95.7%, 95.7% vs 91.3%, 73.9%, 65.2%;p=0.0085). Multivariable Cox regression identified PA-HAIC (HR=0.20, 95% CI:0.02– 0.71;p=0.020) and intact tumor capsule (HR=0.02, 95% CI:0.00– 0.41;p=0.011) as independent protective factors for RFS, while vascular tumor thrombus (HR=28.02, 95% CI:2.07– 378.81;p=0.012) emerged as a risk factor. Subgroup analyses identified age ≥ 50 years, solitary tumors, BCLC-A stage, absence of MVI, intact capsule, and no vascular thrombus as low-risk factors for early recurrence. Safety profiles showed no significant between-group differences in AE incidence or severity. Conclusion: Among HCC patients with high-risk recurrence factors after surgical resection, PA-HAIC demonstrated significantly prolonged RFS compared to PA-TACE, with a favorable safety profile.

Objectives: Although systemic chemotherapy (SC) is the mainstay for treating unresectable intrahepatic cholangiocarcinoma (ICC), its efficacy is limited and it causes severe systemic side effects. This study focuses on evaluating the effectiveness and safety of hepatic arterial infusion chemotherapy (HAIC) in combination with lenvatinib plus programmed death-1 (PD-1) inhibitors (HLP), compared to SC in combination with lenvatinib plus PD-1 inhibitors (SCLP) for unresectable ICC. Methods: We analyzed patients initially diagnosed with unresectable ICC at our center between March 2021 and December 2023, classifying them into HLP and SCLP groups according to treatment regimen. This study assessed and compared overall survival (OS), progression-free survival (PFS), tumor response, and safety outcomes across the two treatment groups. Results: This study enrolled 53 subjects in total; 25 were treated with HLP and 28 with SCLP. The two groups showed well-matched baseline characteristics. The HLP group reported an extended median OS (12.8 vs. 11.0 months, p = 0.310) and a prolonged median PFS (8.8 vs. 6.4 months, p = 0.043), compared to the SCLP group. The HLP group had a better objective response rate (ORR) (52% vs. 25%, p = 0.043) and disease control rate (DCR) (96% vs. 78.6%, p = 0.104). Based on OS (p = 0.019) and PFS (p = 0.032) results, those without extrahepatic metastasis seemed to benefit more significantly from the HLP regimen than from the SCLP regimen. The HLP group experienced fewer grade 3–4 adverse events (AEs) than the SCLP group. Conclusions: The HLP regimen for unresectable ICC is an effective and safe strategy and is potentially better suited for patients without extrahepatic metastases.

With the development of immunotherapy, immune checkpoint inhibitors (ICIs) are widely used in clinical oncology and have achieved good results. ICIs could induce immune-related adverse events (irAEs) in cancer treatment, which warrant sufficient attention. Among them, immune myositis can manifest severe symptoms affecting the whole body, and immune myocarditis occurs with a low incidence but high fatality rate. Here we report a case of grade 3/4 adverse reactions in a patient with partial hepatectomy for malignancy after using ICIs and describe the clinical presentation, laboratory results, treatment, and prognosis. It emphasizes that clinicians should focus on being alert to irAEs in liver cancer patients who have received ICI therapy. The case we present is a 56-year-old male diagnosed with hepatocellular carcinoma. Right hepatic lobectomy was performed in April 2019. Postoperative follow-up showed that transcatheter arterial chemoembolization (TACE) combined with sorafenib (400 mg twice daily) failed to stop the recurrence of the tumor. In December 2020, the patient started to use Camrelizumab injections (200mg/injection every 21 days as a cycle). After 3 cycles, the patient had decreased muscle strength in both lower extremities with chest tightness, dyspnea, and expectoration (whitish sputum). The diagnosis was ICIs injection-induced immune myocarditis and myositis accompanied. The patient’s condition improved considerably by steroid pulse therapy timely. The case emphasizes that clinicians should focus on being alert to irAEs in liver cancer patients who have received ICI therapy.

Circular RNAs have a unique covalent closed-loop structure, which is mainly formed by the reverse splicing of exons from a precursor mRNA. With the development of key technologies such as high-throughput sequencing and the advancement of bioinformatics in recent years, our understanding of circular RNAs has become increasingly more detailed, and their abnormal expression in a variety of cancers has attracted increasing attention. Studies have shown that circSNARCA5 not only plays a crucial role in the occurrence and development of cancer but may also serve as a reliable indicator for tumor screening or a good marker for evaluating cancer prognosis. Nevertheless, there are no reviews focusing on the relationship between circSMARCA5 and cancer. Therefore, we will first explain the main biological characteristics of circSMARCA5, such as biogenesis and biological effects. Then, the focus will be on its role and significance in cancer. Finally, we will summarize the known information on circSMARCA5 in cancer and discuss future research prospects.

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.

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.

Targeting protein for Xenopus kinesin‐like protein 2 (TPX2) is a microtubule‐associated protein that plays a pivotal part in the formation of spindles. There is accumulating evidence that the expression of TPX2 is upregulated in many kinds of human cancers and that this protein is involved in the occurrence and progression of tumors. The purpose of this meta‐analysis was to investigate the relationship between the overexpression of TPX2 and poor prognosis in cancer patients. A total of 18 eligible studies encompassing 3115 patients were included by searching relevant databases. Hazard ratios (HRs) or odds ratios (ORs) with 95% confidence intervals (CIs) were pooled under random‐/fixed‐effect models. After calculation, the results showed that patients with increased TPX2 expression had a significantly shorter overall survival (HR = 2.21; 95% CI: 1.70–2.86), and disease‐free survival (HR = 2.10; 95% CI: 1.67–2.64). In addition, it was found that increased TPX2 expression was significantly associated with TNM stage (OR = 2.17; 95% CI:1.42–3.32), lymph node metastasis (OR = 2.98; 95% CI: 2.28–3.89), distant metastasis (OR = 2.25; 95% CI:1.03–4.92), and vascular invasion (OR = 2.22; 95% CI:1.26–3.91). Nevertheless, there was no significant correlation between increased expression of TPX2 and either gender, tumor differentiation, or tumor size. Thus, we can come to the conclusion that the overexpression of TPX2 is related to poor clinical outcomes and can be used as a biomarker for the prognosis of patients with cancer.

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.