Clinical & Translational Oncology最新文献

Background: Programmed death ligand 1 (PD-L1) expression, assessed by the combined positive score (CPS), is an established predictive biomarker for first-line chemo-immunotherapy in metastatic triple-negative breast cancer (mTNBC). In routine practice, CPS testing is heterogeneous and its relationship with outcomes in later-line, sacituzumab govitecan (SG)-treated patients with mTNBC is not well described. We aimed to assess clinicopathological correlates of CPS and its association with survival in this cohort.

Methods: We conducted a retrospective, multicenter study within the Central European Breast Cancer Collaboration (CEBCC)-102 project. CPS was locally assessed by validated immunohistochemistry. Survival outcomes: overall survival (OS), post-metastatic survival (PMS), and metastasis-free interval, were assessed with the Kaplan-Meier method.

Results: Of 303 women from the Czech Republic, Poland, and Slovakia with mTNBC treated with SG in ≥ 2 line, 107 (35.3%) with available CPS results were included in this analysis. CPS was positive (≥ 10) in 51/107 patients (47.7%) without significant demographic or disease-specific differences. During a median follow-up of 40 months, CPS-positive status may suggest worse outcomes in this cohort in multivariate analysis despite partial first-line chemo-immunotherapy exposure: OS 41.6 versus 67.7 months (HR 2.2, 95% CI: 1.1-4.5, p = 0.027) and PMS 20.2 versus 27.1 months (HR = 2.3, 95% CI: 1.2-4.2, p = 0.009).

Conclusions: In this selected cohort, CPS status did not correlate with clinicopathological characteristics, but CPS-positive status was associated with inferior survival outcomes. Given the selection and survivor bias inherent to later-line treatment cohorts and the incomplete availability of CPS, these findings should be considered hypothesis-generating.

Background: Medulloblastoma is similar to other common tumors in the posterior cranial fossa of children in terms of the onset and clinical manifestations. Still, its main treatment methods, surgical methods and prognosis are quite different. Therefore, there is an urgent need for finding biomarkers for differential diagnosis.

Purpose: The purpose of this study was to identify new lipids and differential metabolic pathways by analyzing the significantly different lipids present in the plasma of children with medulloblastoma in comparison to those with other intracranial tumors.

Methods: In this study, 35 patients with medulloblastoma and 32 matched controls were enrolled. Plasma samples and medical records were collected, and untargeted lipidomics analyses were performed using UHPLC-MS/MS.

Results: A total of 97 differential lipids in the plasma of children with medulloblastoma were identified. Seven differential lipids could be potentially useful in medulloblastoma detection and a diagnostic model was established. The metabolic pathway analysis showed that there were significant differences in patients with medulloblastoma in terms of glycerophospholipid metabolism metabolism, sphingolipid metabolism and linoleic acid metabolism pathways.

Conclusion: The difference in plasma lipid markers between medulloblastoma and other intracranial tumors screened in this study may be useful to support and improve the differential diagnosis of medulloblastoma in children.

Purpose: Emerging evidence suggests an association between the systemic immune-inflammation index (SII) and the survival outcomes of individuals with hepatocellular carcinoma (HCC). However, existing research findings are inconsistent, and no definitive conclusions have been reached. This research aimed to explore the predictive accuracy of the SII in patients with HCC.

Methods: Numerous databases, encompassing PubMed, Embase, Web of Science, and Cochrane Library, were thoroughly retrieved from the database inception until January 14, 2025, to identify studies on the correlation between SII and survival outcomes in HCC. Studies were screened according to pre-established eligibility criteria. The primary endpoints included overall survival (OS), recurrence-free survival (RFS), and progression-free survival (PFS), which were appraised via hazard ratios (HRs) with corresponding 95% confidence intervals (CIs).

Results: 39 high-quality cohort studies involving 47 comparison groups were included in this analysis. As proven by the aggregated data, increased SII was significantly linked to shorter OS (HR = 1.64, 95% CI: 1.45-1.85; p < 0.00001), RFS (HR = 1.68, 95% CI: 1.44-1.96; p < 0.00001), and PFS (HR = 1.48, 95% CI: 1.20-1.82; p = 0.0002) in individuals with HCC. Furthermore, subgroup analyses revealed that age, region, intervention strategy, and SII thresholds affected the validity of SII for predicting the prognosis of HCC.

Conclusion: In HCC patients treated with monotherapy or combination therapy, a higher SII before treatment is significantly associated with shorter OS, RFS, and PFS. SII may serve as an important biological indicator for assessing the prognosis of HCC, providing a critical reference for the scientific and systematic treatment of HCC.

Background: DNA ploidy (P), stroma fraction (S), and nucleotyping (N), collectively known as PSN, have demonstrated prognostic accuracy in various stages of colorectal cancer (CRC). However, the prognostic value of the PSN panel in stage IIIb colon cancer patients receiving CapOX adjuvant chemotherapy remains unclear.

Patients and methods: Postoperative pathological samples from stage IIIb colon cancer patients who underwent radical surgery and postoperative adjuvant chemotherapy at Sun Yat-sen University Cancer Center were retrospectively collected. Kaplan-Meier and Cox regression were performed to compare survival among subgroups of patients stratified by PSN, in order to elucidate the benefits of different durations of adjuvant CapOX chemotherapy.

Result: The PSN low-risk group had the highest 5-year DFS (95.77% vs. 83.07% vs. 84.29%, P = 0.023). Multivariate Cox regression analysis identified primary tumor location (HR = 4.166, 95% CI 1.616-10.742, P = 0.003), perineural invasion (HR = 2.358, 95% CI 1.205-4.615, P = 0.012), and PSN high risk (HR = 3.830, 95% CI 1.352-10.853, P = 0.011) as independent predictors of DFS. No significant difference in 5-year DFS and overall survival (OS) was observed between patients receiving 4-7 cycles and those receiving 8 cycles of CapOX (DFS: 86.24% vs. 88.77%, P = 0.082; OS: 96.38% vs. 94.23%, P = 0.088). However, in the PSN high-risk group, completing 8 cycles of CapOX significantly improved 5-year DFS and OS compared to 4-7 cycles (DFS: 93.10% vs. 77.04%, P = 0.033; OS: 96.30% vs. 91.24%, P = 0.037). In contrast, no significant difference in DFS was observed in the IDEA (International Duration Evaluation of Adjuvant therapy)-based high-risk group (DFS: 85.85% vs. 80.75%, P = 0.062; OS: 97.56% vs. 87.05%, P = 0.598).

Conclusion: The PSN panel effectively stratifies stage IIIb colon cancer, aiding in optimized adjuvant chemotherapy duration determination.

Background: In Egypt, bladder cancer is the second most common cancer among men and the fourth most common cancer in the population. It is tightly associated with genetic alterations. Microtubule-associated protein 1 light chain 3B (LC3) is a unique marker of autophagosomes. Beclin-1 participates in the formation of the autophagosome by mediating the localization of other autophagy proteins to the membrane of the pre-autophagosome. Impaired autophagy is linked to the development of several diseases as cancer and autoimmunity. This work aims to investigate the significance of LC3 and beclin-1 immunohistochemical and gene expressions in bladder cancer diagnosis.

Methods: This study included seventy-four tissue samples of primary urothelial bladder cancer. The tissues were investigated for gene expression, as well as histopathological and immunohistochemical analysis. The genetic and immunohistochemical expressions were correlated with the clinicopathological data.

Results: In the cancerous tissues, there were significant upregulations of LC3 and beclin-1 mRNA and protein expression compared to the adjacent control tissues (P < 0.001 for each). A non-significant positive correlation between LC3 and beclin-1 expression was detected (r =0.212 , P=0.21). Receiver operating curve (ROC) results showed that LC3 at a cut-off point of ≥ 4.3 could be a potential diagnostic marker of bladder cancer with a sensitivity of 96.2% and a specificity of 90.6% (P < 0.001). In addition, beclin-1 at a cut-off point ≥ 2.3 could be a predictor of bladder cancer with a sensitivity of 98% and a specificity of 89% (P < 0.001).

Conclusion: LC3 and beclin-1 expressions can be possible diagnostic markers of bladder cancer. Additionally, they are associated with tumor grade and stage.

Background: Cancer cachexia is a multifactorial syndrome affecting cancer prognosis and immune microenvironment. However, the roles of cachexia-related genes (CRGs) in breast cancer remain unclear.

Methods: We performed differential expression analysis and weighted gene co-expression network analysis (WGCNA) on TCGA-BRCA data to identify key CRGs. A prognostic model was constructed using LASSO-Cox regression. Immune infiltration and treatment sensitivity were assessed, and single-cell RNA-seq analyses were conducted to explore gene function and cell-cell interactions.

Results: A total of 82 CRGs were identified, and an 11-gene prognostic model was constructed, showing high predictive accuracy across multiple cohorts. Based on this model, we created a new risk score (Cachexia-related Risk Score for Breast Cancer, CRSBC) to categorize patients into high and low-risk groups. Low-risk patients had a better prognosis and good immune infiltration with higher sensitivity to immunotherapy. Single-cell analysis revealed HCCS as a key gene enriched in epithelial cells (breast cancer cells) and involved in macrophages recruitment via the MIF signaling pathway.

Conclusions: This study reveals the prognostic and immunological significance of CRGs in breast cancer and highlights HCCS as a potential therapeutic target.

Purpose: Characterization of the management and outcomes of patients diagnosed with hepatocellular carcinoma (HCC) and treated with systemic therapy who were included in the Spanish gastrointestinal RETUD registry.

Methods/patients: This is a retrospective, registry-based, non-interventional, multicenter study conducted in Spain (NCT06711211, retrospectively registered in Dec-2024). This cohort from the RETUD registry includes adult patients diagnosed with HCC and treated with systemic therapy between Jan-2017 and Feb-2024. Sociodemographic, clinical, therapeutic and survival data are analyzed descriptively.

Results: Four hundred and sixty nine patients were included (median age: 65.8 years; 90.2% males; 98.1% Caucasian). At diagnosis, 51.8% presented a clinical stage of Barcelona Clinic Liver Cancer (BCLC)-C. At the start of systemic treatment, 34.5% and 30.3% of the patients showed extrahepatic spread of the disease and main portal vein invasion, respectively. The most frequently administered first-line systemic therapies were sorafenib (57.1%), atezolizumab/bevacizumab (27.7%) and lenvatinib (7.5%). More than a third of the cohort (37.1%) received locoregional treatment at any time (before, concurrent and/or after systemic treatment). Overall, the median progression-free survival (PFS) and overall survival (OS) were 5.1 and 9.8 months, respectively. Patients receiving atezolizumab/bevacizumab showed the longest PFS (10.6 months) and OS (14.0 months) of all treatment groups and a numerically higher objective response rate (ORR) compared to the overall population (31.0% vs 12.5%).

Conclusions: This study offers valuable insights into the clinical characteristics, management, and outcomes of HCC patients in Spain in a real-world setting. Our results suggest potential benefits of immunotherapy-based combinations over other available alternatives, supporting findings from interventional and real-world studies.

Prostate cancer (PCa) continues to represent a substantial public health issue and constitutes one of the foremost etiologies of mortality among men, with increasing incidence rates observed in both developing and industrialized regions. Conventional treatment methods, including surgery followed by chemotherapy or radiotherapy, often yield unacceptable results. Consequently, there is an urgent requirement for the advancement of innovative and more efficacious therapeutic approaches. Immunotherapy offers a compelling and innovative approach to treating PCa by strengthening the immune system's capacity to recognize and eliminate neoplastic cells, suppress recurrence, and prevent metastatic progression. Among immunotherapeutic methods, targeting immune checkpoints has proven to be a notably efficacious approach. CTLA-4 (cytotoxic T lymphocyte-associated antigen-4) is an immune checkpoint molecule expressed on activated T lymphocytes that play a crucial role in regulating the cell cycle, controlling T cell proliferation, and modulating cytokine secretion. Currently, anti-CTLA-4 agents are extensively utilized in clinical research studies across various cancer types. These monoclonal antibodies (mAbs), whether administered either as a standalone therapy or in conjunction with other therapeutic modalities, have significantly enhanced the immune system's ability to suppress cancerous cells as well as have contributed to improved cancer outcomes. Thus, immune checkpoint inhibitors could hold considerable promise for PCa therapy, either as standalone treatments or alongside conventional approaches. In this review, we investigate the function of CTLA-4, and the therapeutic prospects of its inhibition in the context of PCa management.

Colorectal liver metastasis (CRLM) is a major complication of colorectal cancer (CRC), significantly affecting prognosis and survival. Despite advancements in treatment, the management of CRLM remains challenging, primarily due to the complex molecular mechanisms involved. The key molecular pathways that contribute to CRLM development include the Wnt/β-catenin signaling, epidermal growth factor receptor (EGFR), and angiogenesis pathways. These pathways regulate critical processes such as tumor cell proliferation, invasion, and metastasis, and are central to the formation and progression of CRLM. Advances in molecular biology have provided a deeper understanding of these pathways, enabling the development of targeted therapies aimed at improving treatment outcomes. This review presents a detailed analysis of the molecular pathways involved in CRLM, the current status of targeted therapies, and ongoing challenges in the treatment of CRLM. We examine preclinical and clinical developments in targeting these pathways, including Wnt pathway inhibitors, EGFR inhibitors, and anti-angiogenic therapies. In addition, the review discusses ongoing challenges, such as resistance mechanisms, and the potential for combination therapies to improve clinical outcomes. Ultimately, this article highlights the promise of personalized approaches, where molecular profiling can guide therapeutic choices to improve patient outcomes.

Purpose: A chromatin remodeling-related gene, cat eye syndrome chromosome region, candidate 2 (CECR2) was identified as candidate gene associated with aggressive phenotypes of esophageal squamous cell carcinoma (ESCC) in a transcriptome analysis. Here, we aimed to elucidate its role and potential for clinical application.

Methods: We evaluated ESCC cell lines modulating CECR2 expression in vitro. Signaling analysis and inhibitor experiments were conducted to reveal its potential mechanism. Mouse subcutaneous models were established to confirm the effect of knockdown and inhibitor. Expressions of CECR2 on mRNA level were analyzed by qPCR and protein level by TMA, respectively, in two cohorts.

Results: CECR2 was significantly upregulated in cancer tissue compared to normal tissue. CECR2 knockdown suppressed metastasis-related biological functions of ESCC cells and increased the sensitivity to principal anticancer reagents for treatment of ESCC, 5-FU and cisplatin. In addition, forced overexpression of CECR2 enhanced proliferation of low-CECR2-expressed cell line. Mechanistically, CECR2 upregulates NF-κB signaling, downregulates acetylated p53 expressions, and activates AKT signaling to enhance NF-κB signaling. Pharmacological inhibition of CECR2 by NVS-CECR2-1 induced cell apoptosis. In mouse subcutaneous models, permanent knockdown mediated by shCECR2 significantly inhibited tumor growth compared to shControl group; tumor growth was inhibited by a continual cycle of intraperitoneal administration of NVS-CECR2-1 compared to PBS only group. Analysis of two cohorts both demonstrated a significant association between high CECR2 mRNA/protein expression levels and poor prognosis.

Conclusion: Upregulation of CECR2 in ESCC promotes tumor aggressiveness and may serve as a potential therapeutic target for the treatment of ESCC.