Clinical and Translational Oncology最新文献

Objective

To investigate the expression of long non-coding RNA lncSNHG16 in hepatocellular carcinoma (HCC), associations between its expression and patient survival, and its potential role in regulating autophagy in the disease.

Methods

Expression of lncSNHG16 was measured using quantitative real-time PCR in HCC cells in culture and HCC tissues from patients. Effects of lncSNHG16 overexpression were examined in HCC cultures using assays of cell proliferation, wound healing, and migration or invasion in Transwell dishes. Effects of lncSNHG16 overexpression were also examined in subcutaneous tumor in mice. Relationships of lncSNHG16 expression to autophagy and apoptosis in HCC cultures were explored using western blotting and flow cytometry.

Results

Higher lncSNHG16 expression in HCC tissues was associated with significantly worse overall and recurrence-free survival of patients. Overexpressing lncSNHG16 in HCC cell culture promoted cell proliferation, migration, and invasion while suppressing apoptosis. lncSNHG16 was associated with upregulation of STAT3 as well as inhibition of autophagy and associated apoptosis. Overexpressing lncSNHG16 accelerated tumor growth and weight in mice.

Conclusion

The non-coding RNA lncSNHG16 suppresses autophagy and associated apoptosis in HCC, making it a potential therapeutic target.

Purpose

Cytoreductive Surgery (CRS) ± Hyperthermic Intraperitoneal Chemotherapy (HIPEC) is associated with a high incidence of postoperative morbidity. Our aim was to identify independent, potentially actionable perioperative predictors of major complications.

Methods

We reviewed patients who underwent CRS ± HIPEC from June 2020 to January 2022 at a high-volume center. Postoperative complications were categorized using the Comprehensive Complication Index, with the upper quartile defining major complications. Multivariate logistic analysis identified predictive and protective factors.

Results

Of 168 patients, 119 (70.8%) underwent HIPEC. Mean Comprehensive Complication Index was 12.6 (12.7) and upper quartile cut-off was 22.6. Medical complications were more frequent but less severe than surgical (63% vs 18%). Forty-six patients (27.4%) comprised the “major complications” group (mean CCI 30.1 vs 6.3). Multivariate logistic regression showed that heart disease (RR 1.9; 95% CI: 1.1 to 3.3), number of anastomoses (RR 2.4; 95% CI:1.3 to 4.6) and first 24-h fluid balance (RR 1.1; 95% CI: 1.1 to 1.2), were independently associated as risk factors for major complications, while opioid-free anesthesia (RR 0.6; 95% CI: 0.3 to 0.9) and high preoperative hemoglobin (RR 0.9; CI 95%: 0.9 to 0.9) were independent-protective factors.

Conclusion

Preoperative heart diseases, number of anastomoses and first 24 h-fluid balance are independent risk factors for major postoperative complications, while high preoperative hemoglobin and opioid-free anesthesia are protective. Correction of anemia prior to surgery, avoiding positive fluid balance and incorporation of opioid-free anesthesia strategy are potential actionable measures to reduce postoperative morbidity.

Background

Biliary tract cancer (BTC) is a highly heterogeneous aggressive tumor, and advanced patients have poor prognosis. This work aimed to evaluate the efficacy and safety of camrelizumab combined with chemotherapy in treating advanced BTC, and to explore predictive biomarkers for distinguishing effective population.

Methods

183 advanced BTC patients admitted from September 2018 to September 2021 were retrospectively selected. 93 patients were treated with camrelizumab combined with chemotherapy (C+C group) and 90 patients were treated with chemotherapy alone (C group). Objective response rate (ORR), disease control rate (DCR), median progression-free survival (mPFS), and median overall survival (mOS) were analyzed between two groups. Peripheral blood lymphocyte subsets were assessed by flow cytometry pre- and post-treatment.

Results

The mPFS (6.9 months) and mOS (12.1 months) in the C+C group were significantly longer than those in the C group, which were 5.2 months and 9.8 months respectively (HR 0.46, 95% CI 0.38–0.54, p=0.017; HR 0.39, 95% CI 0.32–0.47, p=0.033). The percentage of Total T, CD4+T, natural killer (NK) cells, lymphocyte, and CD4+/CD8+ cell ratios were significantly increased in effective patients after C+C treatment, but didn’t increase in progressive disease (PD) patients. Higher percentage of Total T, CD4+T, and higher CD4+/CD8+ cell ratios post-treatment were associated with longer OS.

Conclusions

Camrelizumab combining chemotherapy significantly prolonged the mPFS and mOS of advanced BTC patients. Immunotherapy may improve the immune status of advanced patients, and immunotherapy efficacy might be predicted based on the peripheral blood lymphocyte subsets.

Purpose

In the last decade trastuzumab biosimilars became more and more frequent. Among their uses, from several years, they have been available in Europe for the treatment of HER2-positive metastatic breast cancer, as an alternative to Herceptin®.

Methods/Patients

This meta-analysis aimed to analyze the available literature with particular focus on phase 3 randomized clinical trials (RCTs) comparing adverse events between trastuzumab biosimilar and originator. A systematic review was conducted in Pubmed and Scopus to include all phase 3 RCTs related to trastuzumab in patients with HER2-positive breast cancer and published up to July 31, 2023. Of the 508 records identified, 14 articles were meta-analyzed for safety information, including serious treatment emergent adverse events, death-related adverse events, neutropenia, leukopenia, infections, increased ALT, increased AST, anti-drug antibody, and neutralizing antibody.

Results

Included patients had an early breast cancer (N=2,877) or a metastatic breast cancer (N=2,603). No significant difference in death-related adverse events was found for trastuzumab biosimilar and originator when evaluated for an early breast cancer in the neoadjuvant phase (Risk Ratio [RR], 1.30; 95% confidence interval [CI], 0.47-3.59; I2 = 0%; p = 0.57) and overall (RR, 0.43; 95%CI, 0.11-1.66; I2 = 20%; p = 0.26), and for metastatic breast cancer (RR, 0.61; 95%CI, 0.30-1.26; I2 = 0%; p = 0.85).

Conclusions

No difference was also observed for all other safety outcomes as in accordance with clinical studies necessary for the registration and approval of a biosimilar at a European level.

Targeting tumor angiogenesis, the formation of new blood vessels supporting cancer growth and spread, has been an intense focus for therapy development. However, benefits from anti-angiogenic drugs like bevacizumab have been limited by resistance stemming from activation of compensatory pathways. Recent immunotherapy advances have sparked interest in novel immunologic approaches that can induce more durable vascular pruning and overcome limitations of existing angiogenesis inhibitors. This review comprehensively examines these emerging strategies, including modulating tumor-associated macrophages, therapeutic cancer vaccines, engineered nanobodies and T cells, anti-angiogenic cytokines/chemokines, and immunomodulatory drugs like thalidomide analogs. For each approach, the molecular mechanisms, preclinical/clinical data, and potential advantages over conventional drugs are discussed. Innovative therapeutic platforms like nanoparticle delivery systems are explored. Moreover, the importance of combining agents with distinct mechanisms to prevent resistance is evaluated. As tumors hijack angiogenesis for growth, harnessing the immune system’s specificity to disrupt this process represents a promising anti-cancer strategy covered by this review.

Background

Cancer driver genes (CDGs) have been reported as key factors influencing the progression of lung adenocarcinoma (LUAD). However, the role of CDGs in LUAD prognosis has not been fully elucidated.

Methods

LUAD transcriptome data and CDG-related data were obtained from public databases and literature. Differentially expressed CDGs (DE-CDGs) greatly associated with LUAD survival (P < 0.05) were identified to establish a prognostic model. In addition, immune analysis of high-risk (HR) and low-risk (LR) groups was conducted by utilizing the CIBERSORT and single sample gene set enrichment analysis (ssGSEA) algorithms to assess immune differences. Subsequently, mutation analysis was conducted using maftools. Finally, candidate drugs were identified using the CellMiner database.

Results

40 DE-CDGs significantly associated with LUAD survival and 11 DE-CDGs associated with prognosis were identified through screening. Regression analysis revealed that risk score can independently predict LUAD prognosis (P < 0.05). Immune landscape analysis revealed that compared to the HR group, the LR group had higher immune scores and high infiltration of various immune cells such as follicular helper B cells and T cells. Mutation landscape analysis demonstrated that missense mutation was the most common mutation type in both risk groups. Drug prediction analysis revealed strong correlations of fulvestrant, S-63845, sapacitabine, lomustine, BLU-667, SR16157, motesanib, AZD-9496, XK-469, dimethylfasudil, P-529, and imatinib with the model genes, suggesting their potential as candidate drugs targeting the model genes.

Conclusion

This study identified 11 effective biomarkers, DE-CDGs, which can predict LUAD prognosis and explored the biological significance of CDGs in LUAD prognosis, immunotherapy, and treatment.

Objectives

Although the discussion about oral mucositis in Head and Neck Cancer (HNC) patients has become a prominent issue, its incidence and influencing factors have not been thoroughly synthesized. This meta-analysis aims to integrate the prevalence and associated factors of radiation-induced oral mucositis among HNC patients.

Methods

This study searched the following electronic databases: PubMed, the Cochrane Database, the Web of Science, EMBASE, CNKI, the Wanfang Database, and the VIP Database. The publication timeframe for the included studies ranged from January 2005 until January 2024. Two investigators used the NOS scale and AHRQ evaluation criteria for quality evaluation. All qualified studies and statistical analyses were conducted using RevMan 5.2 and Stata 17.0.

Results

Thirty eligible studies were included in the analysis. The results show that the prevalence of radiation-induced oral mucositis in HNC patients was 94% [95% CI (89%, 98%)]. Furthermore, the prevalence of severe radiation-induced oral mucositis in HNC patients is 37% [95%CI (29%, 45%)]. Chemotherapy, smoking history, diabetes, oral PH ≤ 7.0, and alcohol consumption are the main risk factors for radioactive oral mucositis. In addition, BMI > 24.0 kg/m², no use of antibiotics, and no use of oral mucosal protective agents are associated with radioactive oral mucositis.

Conclusions

This meta-analysis underscores a significantly high prevalence of radiation-induced oral mucositis in HNC patients. Establishing healthy lifestyle habits and maintaining a healthy oral environment are pivotal in preventing radiation-induced oral mucositis.

Purpose

We developed a predictive model to assess the risk of major bleeding (MB) within 6 months of primary venous thromboembolism (VTE) in cancer patients receiving anticoagulant treatment. We also sought to describe the prevalence and incidence of VTE in cancer patients, and to describe clinical characteristics at baseline and bleeding events during follow-up in patients receiving anticoagulants.

Methods

This observational, retrospective, and multicenter study used natural language processing and machine learning (ML), to analyze unstructured clinical data from electronic health records from nine Spanish hospitals between 2014 and 2018. All adult cancer patients with VTE receiving anticoagulants were included. Both clinically- and ML-driven feature selection was performed to identify MB predictors. Logistic regression (LR), decision tree (DT), and random forest (RF) algorithms were used to train predictive models, which were validated in a hold-out dataset and compared to the previously developed CAT-BLEED score.

Results

Of the 2,893,108 cancer patients screened, in-hospital VTE prevalence was 5.8% and the annual incidence ranged from 2.7 to 3.9%. We identified 21,227 patients with active cancer and VTE receiving anticoagulants (53.9% men, median age of 70 years). MB events after VTE diagnosis occurred in 10.9% of patients within the first six months. MB predictors included: hemoglobin, metastasis, age, platelets, leukocytes, and serum creatinine. The LR, DT, and RF models had AUC-ROC (95% confidence interval) values of 0.60 (0.55, 0.65), 0.60 (0.55, 0.65), and 0.61 (0.56, 0.66), respectively. These models outperformed the CAT-BLEED score with values of 0.53 (0.48, 0.59).

Conclusions

Our study shows encouraging results in identifying anticoagulated patients with cancer-associated VTE who are at high risk of MB.

Purpose

The epidemiologic data of metabolic associated fatty liver disease (MAFLD) in breast cancer (BC) patients remains limited. We aimed to investigate the prevalence and clinicopathological characteristics of hepatic steatosis (HS) and MAFLD in Chinese BC women at initial diagnosis.

Methods

3217 non-metastatic primary BC women with MAFLD evaluation indexes at initial diagnosis and 32,170 age-matched (in a 1:10 ratio) contemporaneous health check-up women were enrolled.

Results

The prevalence of HS (21.5% vs. 19.7%, p = 0.013) and MAFLD (20.8% vs. 18.6%, p = 0.002) were significantly higher in BC women than in health check-ups, respectively. Meanwhile, the prevalence of HS/MAFLD among elderly BC women (≥ 60 years) was significantly higher than the health check-ups (38.7%/37.6% vs 31.9%/30.8%), respectively. In BC women with HS/MAFLD, the prevalence of overweight/obesity was up to 85.7%/88.6%, dyslipidemia and elevated blood pressure were 63.2%/63.7% and 59.7%/61.7%, respectively. No statistical significance of the expressions of estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor 2 (HER-2) and Ki67 were found between BC women with HS/MAFLD and BC women without HS/MAFLD. After adjustment, BC women with HS showed significantly higher risk of lymph node metastasis than BC women without HS. Subjects with HS/MAFLD had higher risks of overweight/obesity, dyslipidemia, elevated blood pressure, hyperuricemia, and elevated enzymes than those without HS/MAFLD.

Conclusions

Compared with health check-ups, BC patients have higher prevalence of HS/MAFLD. HS/MAFLD coexist with high prevalence of metabolic complications, and the risk of lymph node metastasis was significantly higher in BC women with HS than in BC women without HS.

Objective

This study aimed to explore the Liquid–liquid phase separation (LLPS)-related genes associated with the prognosis of bladder cancer (BCa) and assess the potential application of LLPS-related prognostic signature for predicting prognosis in BCa patients.

Methods

Clinical information and transcriptome data of BCa patients were extracted from the Cancer Genome Atlas-BLCA (TCGA-BLCA) database and the GSE13507 database. Furthermore, 108 BCa patients who received treatment at our institution were subjected to a retrospective analysis. The least absolute shrinkage and selection operator (LASSO) analysis was performed to develop an LLPS-related prognostic signature for BCa. The CCK8, wound healing and Transwell assays were performed.

Results

Based on 62 differentially expressed LLPS-related genes (DELRGs), three DELRGs were screened by LASSO analysis including kallikrein-related peptidase 5 (KLK5), monoacylglycerol O-acyltransferase 2 (MOGAT2) and S100 calcium-binding protein A7 (S100A7). Based on three DELRGs, a novel LLPS-related prognostic signature was constructed for individualized prognosis assessment. Kaplan–Meier curve analyses showed that LLPS-related prognostic signature was significantly correlated with overall survival (OS) of BCa. ROC analyses demonstrated the LLPS-related prognostic signature performed well in predicting the prognosis of BCa patients in the training group (the area under the curve (AUC) = 0.733), which was externally verified in the validation cohort 1 (AUC = 0.794) and validation cohort 2 (AUC = 0.766). Further experiments demonstrated that inhibiting KLK5 could affect the proliferation, migration, and invasion of BCa cells.

Conclusions

In this study, a novel LLPS-related prognostic signature was successfully developed and validated, demonstrating strong performance in predicting the prognosis of BCa patients.