Clinical & Translational Oncology最新文献

Introduction: Due to its lack of conventional surface receptors, triple-negative breast cancer (TNBC) is inherently resistant to most targeted therapies. MAL2 overexpression prompts endocytosis, conferring resistance to novel therapeutics. This study explores the role of MAL2 and PD-L1 in TNBC patients' prognosis.

Methods: We performed immunohistochemical analysis on 111 TNBC samples collected from 76 patients and evaluated the expression of MAL2 and PD-1. We expanded the study by including The Cancer Genome Atlas (TCGA) cohort.

Results: MAL2 expression did not correlate with stage, grade, tumor size, lymph node invasion, metastasis, and PD-1 expression. Patients with high MAL2 had significantly lower 5-year survival rates (71.33% vs. 89.59%, p = 0.0224). In the tissue microarray cohort (TMA), node invasions, size, recurrence, and low MAL2 (HR 0.29 [CI 95% 0.087-0.95]; p < 0.05) predicted longer patients' survival. In the TCGA cohort, patients with low MAL2 had significantly longer overall survival and disease-specific survival than patients with high MAL2. Older age and high MAL2 expression were the only independent predictors of shorter patient survival in the BRCA TCGA cohort.

Conclusion: High MAL2 predicts unfavorable prognosis in triple-negative breast cancer, and its expression is independent of PD-1 levels and clinicopathological features of TNBC.

Introduction: Treatment of cancer has been improved with the discovery of biological drugs that act as immune checkpoint inhibitors. In 2017, FDA designated pembrolizumab, an immune checkpoint inhibitor employed in immunotherapy, as the first tissue-agnostic cancer treatment.

Objectives: To review pembrolizumab's use in oncology, gather and examine the latest discoveries regarding the effectiveness of pembrolizumab in cancer treatment.

Methodology: A literature review was conducted through PubMed(Medline) from January 2015 to December 2023 using "pembrolizumab", "cancer" and "treatment" as search terms.

Results: Pembrolizumab demonstrated effectiveness as primary treatment for metastatic nonsmall cell lung cancer, unresectable esophageal cancer, head and neck squamous cell carcinoma and alternative treatment for notable triple-negative breast cancer, biliary, colorectal, endometrial, renal cell, cervical carcinoma, and high microsatellite instability or mismatch repair deficiencies tumors. Pediatric applications include treatment for refractory Hodgkin lymphoma.

Conclusion: Evolving research on pembrolizumab allows a deeper clinical understanding, despite challenges as variable patient responses. Pembrolizumab has emerged as a pivotal breakthrough in cancer treatment, improving patient outcomes and safety.

Objective: Treating aggressive superficial squamous cell carcinoma (SCC) poses challenges due to invasiveness. Palliative care is recommended for inoperable cases with extensive tumors near vital organs, risking disfigurement or functional impairment. Electrochemotherapy (ECT) is an emerging cutaneous tumor treatment, but its efficacy against superficial SCC remains uncertain. This study conducts a systematic review and single-arm meta-analysis to evaluate ECT's effectiveness against superficial SCC and provide current evidence for clinical practice.

Methods: Embase, PubMed and Cochrane Library were searched for studies up to May 2023. The random effects model analyzed complete response (CR) and partial response (PR), with subgroup assessment based on drug dosage, treatment response evaluation, tumor size, primary/recurrent status, and tumor location.

Results: Ten studies involving 162 patients and 208 tumors were included. Pooled CR and PR rates for ECT-treated superficial SCC were 66.5% (95% CI 48.4%-82.5%; I² = 84%) and 20.3% (95% CI 10.5%-32.3%; I² = 70%), respectively. Subgroup analysis indicated ECT's superiority in treating primary tumors (PR: 70%, CR: 30%) and tumors ≤ 3 cm (PR: 81.3%, CR: 10.1%) compared to recurrent tumors (PR: 56.7%, CR: 36.5%) and tumors > 3 cm (PR: 45.2%, CR: 34.4%).

Conclusion: This single-arm meta-analysis confirms ECT's efficacy against superficial SCC, especially in primary tumors and those ≤ 3 cm in diameter. The study highlights the impact of tumor location and response evaluation on ECT's benefits, warranting further investigation through additional research.

Objectives: No head-to-head trials had been performed to estimate the relative effectiveness of poly ADP-ribose polymerase inhibitor (PARPi) and androgen receptor signaling inhibitor (ARSi) in the first-line treatment for metastatic castration-resistant prostate cancer (mCRPC). We aimed to perform a systematic review and network meta-analysis to evaluate the comparative effectiveness of various systemic treatment agents for patients with mCRPC.

Methods: A comprehensive literature search was conducted for abstracts and full-text articles from the database's inception through April 27, 2023. The study concentrated on assessing radiographic progression-free survival (rPFS) for both overall and homologous recombination repair mutation (HRRm) population, with overall survival (OS) as the secondary measure. Under the Bayesian framework, the overall effect was pooled using the fixed-effects model in base case analysis. Scenario analysis using restricted mean survival time (RMST) methods was performed to test the robustness of the results.

Results: Nine studies with 6,830 patients and 8 unique treatment options were included. Network meta-analysis demonstrated that talazoparib in combination with enzalutamide (TALA + ENZA; overall population, hazard ratio [HR], 0.20; 95% credible interval [CrI]: 0.16-0.26; RMST, 3.51; 95% confidence interval [CI] 2.46-4.60; HRRm population, HR, 0.15; 95% CrI: 0.09-0.23; RMST, 4.14; 95% CI 2.84-5.39) was superior to other treatments in the first-line setting in terms of rPFS. The results of Bayesian framework and RMST models showed consistent efficacy ranks. When extrapolated to overall survival benefit, within the Bayesian framework, olaparib plus abiraterone acetate and prednisone (OLAP + AAP) achieved the highest OS benefit for the overall population, which was not statistically significant when compared to TALA + ENZA. However, TALA + ENZA achieved the highest OS benefit at 3 years by applying RMST.

Conclusions: We suggest that talazoparib in combination with enzalutamide is probably a preferred treatment agent for the overall population and HRRm patients with mCRPC. Given the limitations of network framework and the modeling assumptions undertaken to finalize the analyses, results should be cautiously interpreted.

Purpose: The aim of this study was to develop a radiomics model based on magnetic resonance imaging (MRI) for predicting metastasis in soft tissue sarcomas (STSs) treated with surgery.

Methods/patients: MRI and clinical data of 73 patients with STSs of the extremities and trunk were obtained from TCIA database and Jiangsu Cancer Hospital as the training set, data of other 40 patients were retrospectively collected at our institution as the external validation set. Radiomics features were extracted from both intratumoral and peritumoral regions of fat-suppressed T2-weighted images (FS-T2WIs) of patients, and 3D ResNet10 was used to extract deep learning features. Recursive feature elimination (RFE) and least absolute shrinkage and selection operator (LASSO) algorithms were used for the selection of features. Based on 4 different sets of features, 5 machine learning algorithms were used to construct intratumor, peritumor, combined intratumor and peritumor radiomics models and deep learning radiomics (DLR) model. The area under the ROC curve (AUC) and Decision curve analysis (DCA) were used to evaluate the ability of models to predict metastasis.

Results and conclusions: Based on 20 selected features from the deep-learning and radiomics features set, the DLR model was able to predict metastasis in the validation dataset, with an AUC of 0.9770. The DCA and Hosmer-Lemeshow test revealed that the DLR model had good clinical benefit and consistency. By getting richer information from MRI, The DLR model is a noninvasive, low-cost method for predicting the risk of metastasis in STSs, and can help develop appropriate treatment programs.

Background: The Niemann-Pick disease type C1 (NPC1) protein plays a pivotal role in lipid transport, particularly free cholesterol, within lysosomal/late endosomal membranes. Previous studies have highlighted NPC1 as a promising target for cholesterol trafficking and cancer therapy. Nevertheless, the expression of NPC1 in gastric cancer (GC) and its clinical implications remain unexplored. This study aims to investigate NPC1 expression in GC and its correlation with patient prognosis.

Methods: NPC1 expression levels in GC and normal tissues were assessed using the GEPIA database, and survival analysis was conducted via Kaplan‒Meier Plotter. Evaluation of potential biological effects of NPC1 in GC by protein-protein interaction network and GO, KEGG bioenrichment analysis. Immunohistochemistry was performed on surgical samples collected from 306 GC patients. Correlations between NPC1 expression, clinical characteristics, and patient prognosis were analyzed.

Results: NPC1 mRNA expression was elevated in GC tissues compared to normal tissues (P < 0.05) and significantly associated with poorer prognosis. In our cohort of 306 patients, NPC1 exhibited significant upregulation in GC versus adjacent normal tissues (P = 0.031). High NPC1 expression correlated with adverse clinical characteristics, including lymph node metastasis, distant metastasis, and advanced TNM stage (all P < 0.05). Patients with high NPC1 expression experienced notably shorter overall survival (P < 0.001), particularly in stages III and IV (P = 0.003). Multivariate Cox regression analysis identified high NPC1 expression as an independent prognostic factor for GC patients (HR 1.57, 95% CI 1.14-2.18, P = 0.006). Lastly, an optimized nomogram incorporating NPC1, tumor size, and TNM stage was constructed.

Conclusions: NPC1 expression is upregulated in GC and serves as a pivotal prognostic factor for adverse outcomes in GC patients.

Background: Cuproptosis, as a unique modality of regulated cell death, requires the involvement of ubiquitin-binding enzyme UBE2D2. However, the prognostic and immunotherapeutic values of UBE2D2 in pan-cancer remain largely unknown.

Methods: Using UCSC Xena, TIMER, Clinical Proteomic Tumor Analysis Consortium (CPTAC), and Human Protein Atlas (HPA) databases, we aimed to explore the differential expression pattern of UBE2D2 across multiple cancer types and to evaluate its association with patient prognosis, clinical features, and genetic variations. The association between UBE2D2 and immunotherapy response was assessed by gene set enrichment analysis, tumor microenvironment, immune gene co-expression and drug half maximal inhibitory concentration (IC50) analysis.

Results: The mRNA and protein levels of UBE2D2 were markedly elevated in most cancer types, and UBE2D2 exhibited prognostic significance in liver hepatocellular carcinoma (LIHC), kidney chromophobe (KICH), uveal melanomas (UVM), cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC), and kidney renal papillary cell carcinoma (KIRP). UBE2D2 expression was correlated with clinical features, tumor mutation burden, microsatellite instability, and anti-tumor drug resistance in several tumor types. Gene enrichment analysis showed that UBE2D2 was significantly associated with immune-related pathways. The expression level of UBE2D2 was correlated with immune cell infiltration, including CD4 + T cells、Macrophages M2、CD8 + T cells in pan-cancer. PDCD1, CD274 and CTLA4 expression levels were positively correlated with UBE2D2 level in multiple cancers.

Conclusions: We comprehensively investigated the potential value of UBE2D2 as a prognostic and immunotherapeutic predictor for pan-cancer, providing a novel insight for cancer immunotherapy.

Background: Currently, the effectiveness of TACE, Lenvatinib, and PD-1/L1 inhibitors used alone or in combination has been thoroughly reported. However, the differences in effectiveness between these treatment protocols require further verification. To this end, this study employs a Bayesian network meta-analysis to compare the efficacy and safety of TACE, Lenvatinib, and PD-1/L1 inhibitors, whether administered by monotherapy or in combination, providing evidence-based medicine for the treatment of unresectable HCC.

Purpose: This study employed a network meta-analysis to evaluate the efficacy and safety of trans-arterial chemoembolization (TACE), Programmed Cell Death Protein/Ligand 1 (PD-1/L1) inhibitors, and Lenvatinib in the treatment of advanced HCC.

Methods: Literature on the treatment of advanced HCC with TACE, PD-1/L1 inhibitors, and Lenvatinib was searched for in both Chinese and English databases, including PubMed, EMBASE, ClinicalTrials.gov, Cochrane Library, CNKI, and Wanfang. Two researchers conducted independent screening and data extraction, and the meta-analysis was performed using R language with the gemtc package.

Results: After retrieval and screening, a total of 21 articles were included, involving 2052 participants and six treatment modalities: Lenvatinib (L), TACE (T), TACE + Lenvatinib (TL), Lenvatinib + PD-1/L1 inhibitors (LP), TACE + Lenvatinib + PD-1/L1 inhibitors (TLP), and TACE + PD-1/L1 inhibitors (TP). In terms of objective response rate (ORR), the TLP regimen provided the optimal effect. In predicting the best ORR, TLP had the highest (75.5%) probability. In terms of disease control rate (DCR), the TLP regimen showed the best effect. In predicting the best DCR, the TLP again offered the highest (76.1%) probability. In terms of overall survival (OS), the best outcome was observed in the TLP protocol. In predicting the best OS, the TLP holds the highest (86.00%) probability. Furthermore, the best outcome in progression-free survival (PFS) was found in the TLP regimen. In predicting the best PFS, the TLP still holds the highest (97.0%) result.

Conclusion: The combination of TACE, Lenvatinib, and PD-1/L1 inhibitors appears to provide the maximum benefit for inoperable HCC patients.

Aim: To comprehensively analyze trends in myelodysplastic neoplasm (MDS) mortality across Spain (1999-2022), examining sex and regional differences.

Methods: We analyzed nationwide death records and population data, calculating age-standardized mortality rates (ASMRs) and standardized mortality ratios (SMRs) stratified by sex and Autonomous Community (AC). Joinpoint regression identified significant shifts in trends.

Results: Across Spain, MDS mortality risk varied among men, with rates ranging from 1.08 to 4.38 per 100,000 across regions, while women's rates ranged from 1.23 to 2.02. Five regions had higher risks than the national average, while six had lower risks. Joinpoint analysis revealed three periods nationally: a decline until 2008, and an increase until 2017, followed by a significant decrease. Despite the overall stable national trend (-0.5% annual change), significant regional variations emerged. Andalusia stood out with a worrying increase in MDS mortality, while Aragon and Murcia demonstrated promising declines. Extremadura displayed a unique trajectory with an initial rise followed by stabilization, while Galicia exhibited a contrasting trend with an initial decline and subsequent increase. Notably, men consistently faced a higher risk of MDS mortality compared to women, with significant disparities across regions. Extremadura, in particular, showed a marked difference in risk between genders.

Conclusion: MDS mortality trends in Spain are complex, and influenced by gender, region, and time. Further research is needed to understand regional disparities, recent national decline, and higher risk in specific demographics. Tailored interventions based on local factors and targeted research are crucial to address these complexities and improve patient outcomes.

Purpose: Emerging evidence suggests that vaginal micro-environment disorder is closely related to the development of cervical lesions. Low-grade cervical intraepithelial neoplasia (CIN1), as an early stage of cervical lesions, exhibits a high risk of progressing to high-grade lesions or even cervical cancer. However, the effect of vaginal micro-environment on the malignant prognosis of CIN1 remains uncertain.

Methods: A total of 504 patients diagnosed with CIN1 by pathology, who were from the population-based cohorts established in Shanxi Province, China, were enrolled and followed up for 2 years. Micro-environmental factors such as vaginal pH, cleanliness, hydrogen peroxide (H₂O₂), β-glucuronidase (GUSB), leucocyte esterase (LE), and sialidase (SNA) were detected to evaluate their effect on the malignant prognosis of CIN1.

Results: Abnormal vaginal pH (HR = 1.472, 95%CI 1.071-2.022), cleanliness (HR = 1.446, 95%CI 1.067-1.960), H₂O₂ (HR = 1.525, 95%CI 1.155-2.013), GUSB (HR = 1.739, 95%CI 1.235-2.448), LE (HR = 1.434, 95%CI 1.038-1.981), and SNA (HR = 1.411, 95%CI 1.065-1.870) could promote a higher incidence of CIN1 malignant prognosis, and the combined effects of these micro-environmental factors resulted in a nearly twofold increased risk (HR = 2.492, 95%CI 1.773-3.504) compared to any single factor alone, especially under the high-risk human papillomavirus (HR-HPV) infection. Notably, the cumulative incidence of malignant prognosis for CIN1 gradually increased during the early follow-up period, reaching its peak at approximately 8 months, and then stabilizing.

Conclusion: Vaginal micro-environment disorder could promote CIN1 malignant prognosis, particularly in HR-HPV-infected women. Taking micro-environmental factors as the breakthrough, our study provides a feasible vision for preventing early stage cervical lesions.