Clinical & Translational Oncology最新文献

Purpose: Pathological complete response (pCR) after neoadjuvant chemotherapy (NACT) is a validated endpoint for long-term survival in HER2-positive breast cancer. Identifying clinical and biomarker-based predictors of pCR is essential for optimizing treatment strategies. This study investigated the predictive role of nutrition- and inflammation-based indices (HALP, CALLY, PNI, SII, PIV, SIRI, NLR) in determining pCR.

Methods: A total of 169 HER2-positive patients who underwent NACT followed by surgery at Ankara Etlik City Hospital between January 2023 and December 2024 were retrospectively analyzed. Indices were calculated from baseline laboratory values. Receiver operating characteristic (ROC) analysis was used to evaluate discriminatory ability and determine cut-off values for significant variables. Univariate logistic regression was performed initially; variables significant at the univariate level were included in the multivariate model.

Results: The overall pCR rate was 56.8%. ROC analysis identified the CALLY index (AUC = 0.681; p < 0.001) and Ki-67 (AUC = 0.603; p = 0.022) as significant predictors, while HALP, PNI, NLR, PIV, SII, and SIRI lacked predictive value. In univariate analysis, high CALLY (p < 0.001), high Ki-67 (p = 0.012), and pertuzumab-containing regimens [AC + taxane + trastuzumab + pertuzumab (p = 0.003) and docetaxel + trastuzumab + carboplatin + pertuzumab (THCP) (p = 0.004)] were associated with higher pCR, whereas ER positivity was associated with a reduced likelihood of pCR (OR = 0.41; p = 0.011). In multivariate analysis, CALLY (OR = 4.03; p < 0.001), Ki-67 (OR = 2.21; p = 0.038), and pertuzumab-containing regimens remained independent predictors: AC + taxane + trastuzumab + pertuzumab (OR = 3.24; p = 0.020) and THCP (OR = 3.86; p = 0.037). Although ER positivity was significant in univariate analysis, it lost statistical significance in the multivariate model (OR = 0.49; p = 0.072).

Conclusions: High CALLY index and high Ki-67 were found to be statistically significant in predicting pCR, and pertuzumab-containing regimens were shown to increase pCR rates. In contrast, classical histopathological parameters and other immunonutritional scores demonstrated limited predictive value. These findings require validation through prospective, multicenter studies. The limited number of studies investigating the association between pCR and CALLY highlights the originality of our work.

Objective: This study aims to investigate the expression of Chitinase-3-like protein-1 (CHI3L1) in gastric cancer (GC) tissues and serum from patients, analyze the correlation between CHI3L1 expression and GC patients' clinicopathological parameters, evaluate its impact on patient prognosis and the tumor immune microenvironment, and explore the potential of CHI3L1 as a diagnostic biomarker in GC.

Materials and methods: The expression of CHI3L1 in GC was investigated using data from The Cancer Genome Atlas (TCGA) and TIMER databases. The association between CHI3L1 expression and prognosis in GC patients was analyzed through the TCGA database. Serum samples were collected from 87 patients with GC, 38 patients with gastric precancerous lesions, and 42 healthy volunteers. The levels of CHI3L1 in serum specimens were measured via chemiluminescent immunoassay (CLIA), and the receiver operating characteristic (ROC) curve was employed to further evaluate the diagnostic efficacy of CHI3L1. Gene Set Enrichment Analysis (GSEA) was performed using gene sets from the Molecular Signatures Database (MsigDB). Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were conducted on correlated genes obtained from the LinkedOmics database. Additionally, the CIBERSORT algorithm was applied to investigate the correlation between CHI3L1 and gastric cancer immune infiltration, aiming to explore the potential mechanisms of CHI3L1 in GC.

Results: CHI3L1 expression was significantly upregulated in GC (P < 0.05) and exhibited strong correlations with GC subtypes, tumor differentiation grade, primary tumor status, regional lymph node metastasis, distant metastasis, clinical stage, Borrmann classification, and tumor size (all P < 0.05). Prognostic analysis revealed correlations between patient survival and age, primary tumor status, regional lymph node metastasis, distant metastasis, clinical stage, new tumor events, and residual tumor (all P < 0.05). Notably, CHI3L1 demonstrated high diagnostic efficacy for GC (In the TCGA database: AUC = 0.861, P < 0.0001; For the serum samples: AUC = 0.932, P < 0.0001). Gene Set Enrichment Analysis (GSEA) suggested that CHI3L1 is involved in multiple oncogenic signaling pathways, including the NF-κB, IL-17, and ECM-receptor interaction pathways. Functional enrichment analysis further linked CHI3L1 to inflammatory response and immune regulation, while immune infiltration analysis via CIBERSORT indicated significant correlations between CHI3L1 expression and infiltration levels of multiple immune cell types.

Conclusions: CHI3L1, an oncogenic glycoprotein, is highly expressed in GC and involved in immune infiltration, holding promise as a diagnostic biomarker for GC.

Background: Endometrial cancer (EC) is the sixth most common female cancer and may rank fourth in cancer mortality by 2040. TP53 mutations and aberrant p53 expression are associated to aggressive tumor subtypes and poor prognosis, reducing overall survival (OS), disease-free survival, recurrence rates (RcR) and Mortality Risk (MR). The prognostic impact of TP53 mutations in EC remains unclear.

Methods: A systematic search was conducted in PubMed, Embase, and the Cochrane Library. Hazard ratios (HR) and Risk Ratios (RR) with 95% confidence intervals (CI) were combined using random-effects models. Analyses were conducted in RStudio (v4.4.1), and heterogeneity was evaluated using the I² statistic, with p < 0.05 considered significant.

Results: Twenty-four studies comprising 5462 EC patients were included. TP53 mutations and aberrant p53 expression were associated with poorer outcomes. For OS, TP53 mutations had an HR of 2.27 (95% CI 1.47-3.49) and aberrant p53 had an HR of 5.01 (95% CI 2.44-10.30). For DFS, TP53 mutations had an HR of 4.20 (95% CI 1.79-9.86), while aberrant p53 had an HR of 2.17 (95% CI 1.27-3.72). TP53 mutations also increased RcR (RR: 2.88; 95% CI 2.18-3.80) and MR (RR: 2.33; 95% CI 1.11-4.88). Aberrant p53 showed a non-significant trend for recurrence (RR: 3.54; 95% CI 0.95-13.10).

Conclusions: TP53 mutations and abnormal p53 expression in EC patients predict a poorer prognosis, characterized by increased RcR and MR, as well as lower DFS and OS.

DNA methylation, histone modifications, and regulation of non-coding RNA are all epigenetic modifications affecting cancer cells of origin and progression. These changes lead to changed expression of genes, which in turn is the reason for cancer occurrence in the form of inhibition of tumor suppressor genes or activation of oncogenes. Epigenetic changes, as opposed to genetic mutations, are reversible; thus, they seem to be interesting targets for therapeutic interventions. Current review summarizes the various types of epidrugs -DNA methyltransferase inhibitors (DNMTis), histone deacetylase inhibitors (HDACis), histone methyltransferase inhibitors (HMTis), and BET inhibitors-are studied in this review. And the mechanisms of action, therapeutic potential, and clinical applications of epidrugs in several types of cancer, such as solid tumors (breast, lung, colorectal, and brain tumors) and hematological malignancies (acute myeloid leukemia (AML) and multiple myeloma). In addition, we address the challenges faced by epigenetic therapies, such as drug toxicity, off-target effects, and drug resistance. One of the rapidly evolving areas of cancer treatment is bringing new cancer treatments, and the use of epidrugs with conventional treatments, immunotherapy, and targeted therapy is an area. Epidrugs, drugs that control epigenetic pathways, have become substances that could be beneficial in cancer treatment. They can repress normal gene expression, reverse drug resistance, and make tumors penetrable to treatments that are already in place. Following instructions by tumor-specific epigenome analysis, personalized epigenetic therapy has the prospect to tailor the treatment schedule and to enhance medical outcome. Overcoming limitations and forming combination strategies to promote efficacy with less toxicity would foster the epigenetic treatment approach for cancer.

Background: Despite limited research, cancer patients are opting for compounds found in cannabis, like tetrahydrocannabinol (THC) and cannabidiol (CBD), to improve their sleep. The purpose of this study was to examine the therapeutic value of cannabis for sleep.

Methods: Patient-reported symptom responses were obtained from 1962 cancer patients enrolled in the Minnesota Medical Cannabis Program (MMCP) from 2015 to 2023. Multivariable logistic and linear regression models were used to evaluate the associations between changes in reported sleep disturbance scores and the dose of THC, the dose of CBD, and the cannabinoid ratio (THC:CBD). Logistic and linear regression models were adjusted for sex, age, race, ethnicity, body mass index, and MMCP enrollment fee category. Linear regression models were additionally adjusted for baseline sleep disturbance score.

Results: Compared to the highest quintile category of CBD dose, lower dose quintiles were 29-35% less likely to be associated with at least a 30% improvement in sleep disturbance scores. Sleep disturbance scores improved by 1.87 points on a 0-10 ordinal scale for cancer patients with CBD doses in the top quintile, and approximately 1.5 points for doses in lower quintiles. THC and THC:CBD doses were not consistently related to changes in sleep disturbance scores.

Conclusion: Higher CBD doses may be associated with clinically meaningful improvements in sleep in cancer patients enrolled in a medical cannabis program.

Background: Cisplatin (CDDP) resistance represents an urgent clinical challenge. Identifying CDDP-resistant lung adenocarcinoma (LUAD) patients responsive to immunotherapy through novel biomarkers is critical for improving survival outcomes.

Methods: CDDP resistance genes were identified from RNA-seq data of A549 cells in the GEO database. RNA sequencing, genetic mutations, and clinical data of LUAD patients were obtained from TCGA. Patients were split into training and validation cohorts. A prognostic model was developed using LASSO and multivariate Cox regression, with validation in both cohorts. Tumor mutation burden (TMB), immune activity, and functional enrichment analyses (GO, KEGG) were performed to explore the link between lncRNA and CDDP resistance.

Results: Twenty-three CDDP resistance-associated genes were identified from GEO. Co-expression analysis revealed 507 CDDP resistance-linked lncRNAs. Cox regression analysis identified three CDDP resistance-related lncRNAs: ARAP1-AS2, LINC01843, and LINC02198. RT-PCR verified these lncRNAs and representative mRNAs (KIF21B, B3GNT3, PLXNA2). Patients stratified by median risk score showed significantly worse overall survival (OS) and higher mortality in high-risk groups. Univariate/multivariate Cox analyses confirmed the risk score as an independent prognostic factor. A nomogram predicted LUAD survival outcomes. Low-risk patients exhibited significantly lower TMB than high-risk counterparts, with low-risk/high-TMB patients showing optimal OS. The Tumor Immune Dysfunction and Exclusion (TIDE) algorithm revealed significant differences in immune dysfunction, CD8⁺ T cells, cancer-associated fibroblasts (CAF), and tumor-associated macrophages (TAM-M2) between risk groups.

Conclusion: These three CDDP resistance-associated lncRNAs including ARAP1-AS2, LINC01843, and LINC02198, serve as reliable prognostic biomarkers for LUAD. The findings provide insights for immunotherapeutic strategies and personalized treatment development.

Purpose: This meta-analysis evaluated the efficacy of adjuvant ICIs in resected stage IB-IIIA NSCLC following chemotherapy.

Methods: We searched Embase, Cochrane, PubMed, and major oncology conferences for randomized controlled trials (RCTs) comparing adjuvant ICIs with placebo/best supportive care. Outcomes included disease-free survival (DFS), overall survival (OS), and safety. Hazard ratios (HR) and risk ratios (RR) with 95% confidence intervals (CI) were calculated.

Results: Three RCTs (3401 patients) were analyzed. Adjuvant ICIs improved DFS (HR 0.85; p < 0.01) but not OS (HR 0.93; p = 0.43). DFS benefits were observed in subgroups of patients who received prior chemotherapy (HR 0.83), had non-squamous histology (HR 0.75), or had PD-L1 expression of 1-49% (HR 0.82). ICIs increased grade 3-4 (RR 1.42) and grade 5 adverse events (RR 2.33).

Conclusion: This analysis supports the use of adjuvant ICIs in early-stage NSCLC, particularly in patients with non-squamous histology who have received prior adjuvant chemotherapy.

Background: Although allergic predisposition may modulate antitumor immunity, its influence on immune checkpoint blockade remains unclear. We investigated whether a documented drug allergy history affects the outcomes of PD-(L)1 inhibitors in advanced non-small cell lung cancer (NSCLC).

Methods: We retrospectively analyzed 246 patients with stage III-IV NSCLC treated with PD-(L)1 inhibitors at West China Hospital from October 2019 to October 2024, with follow-up through May 2025. Patients were grouped according to drug allergy history. Baseline imbalances were corrected using 1:2 propensity score matching (caliper 0.2) and inverse probability of treatment weighting. The primary endpoint was progression-free survival (PFS); secondary endpoints included overall survival (OS), objective response rate (ORR), and immune-related adverse events (irAEs).

Results: Before adjustment, allergy-positive patients (n = 49) showed higher 1-year PFS than controls (54.4% vs. 35.7%, p = 0.019). After matching, median PFS remained longer (13.6 vs. 6.6 months; hazard ratio 0.61, 95% CI 0.40-0.91, p = 0.017), and 1-year PFS improved (57.0% vs. 33.4%, p = 0.009), whereas 3-year PFS, OS, and ORR were comparable. Weighted analyses and multiple sensitivity tests corroborated these findings. Overall incidences of Grade ≥ 2 or ≥ 3 irAEs were similar; although Grade ≥ 2 gastrointestinal irAEs trended higher in the allergy cohort (6.1% vs. 1.0%, p = 0.054).

Conclusions: A history of drug allergy predicts early clinical benefits, particularly superior 1-year PFS, from PD-(L)1 blockade in advanced NSCLC without increasing severe irAEs. Prospective multicenter studies are needed to confirm these findings and elucidate the underlying mechanisms.

Purpose: The approval of programmed death-ligand 1 (PD-L1) inhibitors in the first line of treatment has transformed the therapeutic landscape of extensive-stage small cell lung cancer (ES-SCLC); real-world (rw) evidence of clinical benefit is currently limited. In this study, we investigated the rw efficacy of first-line chemoimmunotherapy and the role of potential biomarkers.

Methods/patients: We retrospectively assessed patients with SCLC receiving first-line chemoimmunotherapy at Sotiria Thoracic Diseases Hospital of Athens, Athens, Greece. Kaplan-Meier curves were used to calculate real-world progression-free survival (rwPFS) and real-world overall survival (rwOS). Cox proportional hazards regression analysis was utilized to identify associations between patient characteristics and outcomes.

Results: 188 patients were included. Median rwPFS was 6.5 months (95% CI 5.8-7.1 months) and median rwOS was 11.2 months (95% CI 9.1-12.0 months). rwOS was higher in the atezolizumab group compared with the durvalumab group (median, 12.0 vs 9.2 months; hazard ratio [HR], 1.51; 95% CI 1.06-2.15; p = 0.02), similar results were observed for rwPFS (median, 6.5 vs. 6.0 months, HR, 1.55; 95% CI 1.10-2.16; p = 0.01). In multivariate analysis, the difference between atezolizumab and durvalumab was not statistically significant, while lung, bone and liver metastases, ECOG PS, LDH and NLR were associated with an increased risk of death. Associations were utilized for the generation of a novel prognostic score with good discriminatory power (C-statistic: 0.73).

Conclusions: Real-world efficacy of first-line chemoimmunotherapy in patients with ES-SCLC is comparable to randomized trials. The association between prognostic scores and survival outcomes in ES-SCLC should be explored in prospective studies.Query.

Background: MicroRNAs (miRNAs) are short non-coding RNAs that regulate gene expression post-transcriptionally. miR-122 is abnormally expressed in breast cancer, functioning as both a tumor suppressor and oncomiR, however, its role in triple-negative breast cancer (TNBC) remains unclear.

Purpose: In this study we investigate the molecular mechanism of miR-122 in TNBC patients undergoing neoadjuvant chemotherapy (NAC).

Methods: We analyzed the expression of miR-122 and its clinical association in TNBC patients from TCGA and KM-plotter datasets. Functional analysis was performed by modulating miR-122 levels in TNBC cells through antagomiR transfections for knockdown assays, and mimic-miR-122 assays, followed by RT-qPCR, immunoblotting, cell viability and migration assays.

Results: Downregulation of miR-122 in TNBC patients is associated with tumor recurrence but not with pathologic complete response after NAC. Low miR-122 levels in rapid-relapse TNBC patients activate a gene co-expression network enriched in genes linked to migration, invasion, and cell differentiation. Among these, DNA-binding protein BORIS was identified as a target of miR-122. Overexpression of miR-122 inhibited cell migration and BORIS expression. Additionally, BORIS promoted a gene expression profile related to cell differentiation and cytoskeletal components in TNBC tumors deficient of miR-122.

Conclusion: The loss of miR-122 in TNBC tumors is associated with rapid relapse after chemotherapy in patients and allows cell migration by promoting a metastatic-related transcriptomic landscape, including positive modulation of BORIS expression.