Introduction: The aim of the present study was to analyze the expression of matrix metalloproteinase 9 (MMP9) in nasopharyngeal carcinoma (NPC) and its correlation with clinicopathologic features, including the survival of patients with NPC. Methods: Using real-time PCR, we detected the mRNA expression of MMP9 in normal nasopharyngeal tissues and nasopharyngeal carcinoma (NPC) tissues. Using immunohistochemistry analysis, we analyzed MMP9 protein expression in clinicopathologically characterized 164 NPC cases (116 male and 48 female) with age ranging from 17 to 80 years (median = 48.4 years) and 32 normal nasopharyngeal tissues. Cases with greater than or equal to 6 and less than 6 of the score value of cytoplasmic MMP9 immunostaining were regarded as high expression and low expression, respectively. The relationship between the expression levels of MMP9 and clinical features was analyzed. Results: The expression level of MMP9 mRNA was markedly greater in NPC tissues than that in the nasopharyngeal tissues. Immunohistochemical analysis revealed that the protein expression of MMP9 detected in NPC tissues was higher than that in the nasopharyngeal tissues (P = 0.004). In addition, high levels of MMP9 protein were positively correlated with the status of lymph node metastasis (N classification) (P = 0.002) and clinical stage (P < 0.001) of NPC patients. Patients with higher MMP9 expression had a significantly shorter overall survival time than did patients with low MMP9 expression. Multivariate analysis suggested that the level of MMP9 expression was an independent prognostic indicator (P = 0.008) for the survival of patients with NPC. Conclusion: High level of MMP9 expression is a potential unfavorable prognostic factor for patients with NPC.

Background: Circular RNAs (circRNAs) play an important role in the progression of non-small cell lung cancer (NSCLC), especially under tumor hypoxia. However, the precise functions and underlying mechanisms of dysregulated circRNAs in NSCLC are largely unknown. Methods: High-throughput RNA sequencing was performed to identify significantly expressed circRNAs in NSCLC tissues. The functions of circ-0001875 in NSCLC cells were investigated in vitro and in vivo. The regulatory relationships of circ-0001875, miR-31-5p and SP1 were examined by dual luciferase reporter assays and rescue experiments. The signal pathway of epithelial-to-mesenchymal transition and the formation of filopodia were analyzed by western blot and immunofluorescence staining. The binding of SP1 to Alu elements was evaluated by RNA immunoprecipitation, and the HIF1α and SP1 interaction was detected by co-immunoprecipitation. Results: We identified the novel Has_circ_0001875 as a significantly upregulated circRNA in NSCLC tissues and cell lines. circ-0001875 promoted the proliferation and metastasis of NSCLC both in vitro and in vivo, and induced NSCLC cells to extend filopodia. Mechanistically, circ-0001875 sponged miR-31-5p to regulate SP1, influencing epithelial-to-mesenchymal transition via the TGFβ/Smad2 signal pathway. SP1 negatively regulated circ-0001875 formation through an AluSq-dependent feedback loop, which was disrupted by competitive binding of HIF1α to SP1 under hypoxia condition. The circ-0001875/miR-31-5p/SP1 axis was associated with the clinical features and prognosis of NSCLC patients. Conclusions: Our results revealed that the circ-0001875/miR-31-5p/SP1 axis and the complex regulatory loops influence NSCLC progression. These findings provide new insights into the regulation of circRNA formation under tumor hypoxia.

Background: Recent studies have found that ferroptosis-related genes (FRGs) have broad applications in tumor therapy. However, the predictive potential of these genes in lung adenocarcinoma (LUAD) remains to be fully characterized. We aimed to investigate the FRGs that might be potential targets for LUAD. Methods: We screened the RNA sequencing samples from LUAD patients from the GEO database and analyzed the ferroptosis-related differentially expressed genes (DEGs). A functional analysis of DEGs was performed. The risk model was constructed to evaluation and validation FRGs. We explored the immune landscape of LUAD and controls. The value of FRGs in diagnosing LUAD was tested in the GSE30219, GSE37745, GSE0081 datasets, and qPCR was used to verify their diagnostic value in LUAD patients in our hospital. Results: A total of 1327 DEGs in quantitative proteomics were obtained, of which ferroptosis-related DEGs were 259. Enrichment analysis showed significant enrichment in the absorption and metabolism of fatty acids and arachidonic acid. The upregulated genes (GCLC, RRM2, AURKA, SLC7A5, and SLC2A1) and downregulated genes (ANGPTL7, ALOX15, ALOX15B, HSD17B11, IL33, TSC22D3, and DUOX1) were selected as core genes in tissue samples from 62 patients by qPCR. DUOX1 and HSD17B11 were obtained by bioinformatics analysis, both of which showed similar expression trends at the RNA and protein levels. The Kaplan–Meier method showed that DUOX1 and HSD17B11 were closely related to the overall survival (OS) of LUAD patients. Conclusion subsections: Ferroptosis-related genes DUOX1 and HSD17B11 are of considerable value in the diagnosis of LUAD patients. Their low expression suggests an increased recurrence rate and leads to a decrease in the patient quality of life.

Accumulating data demonstrate the robust overall and intracranial activity of trastuzumab deruxtecan (T‐DXd) in HER2‐positive breast cancer brain metastasis (BCBM). Limited data are available on HER2‐low/zero BCBM, as well as patients with symptomatic active BM, leptomeningeal disease (LMD), and poor performance status. This multicenter, retrospective, real‐world study enrolled patients diagnosed with HER2‐positive or low/zero BCBM receiving T‐DXd. Progression‐free survival (PFS), intracranial progression‐free survival (IC‐PFS), overall survival (OS), objective response rate (ORR), disease control rate (DCR), IC‐ORR, IC‐DCR, and adverse events (AEs) were evaluated. From January 2020 to July 2024, 58 HER2‐positive and 30 HER2‐low/zero patients were enrolled. In the HER2‐positive cohort, the median PFS, IC‐PFS, and OS were 11, 13, and 46 months, respectively. ORR and DCR were 65.2% and 91.3% systemically, with IC‐ORR and IC‐DCR of 61.0%/90.2% (RECIST 1.1) and 59.5%/88.1% (RANO‐BM). In the HER2‐low/zero cohort, median PFS, IC‐PFS, and OS were 4, 5, and 26 months. ORR and DCR were 33.3% and 66.7%. IC‐ORR and IC‐DCR were 44.4% and 88.9% by RECIST 1.1 and RANO‐BM. HR+/HER2‐low patients had significantly longer PFS than HR‐/HER2‐low (10 vs. 3 months, p < 0.001). In the LMD cohort, the 12‐month IC‐PFS rates were 67.7% and 60.0% in HER2‐positive and low/zero cohorts. The most common AEs included fatigue (45.9%) and appetite loss (25.2%). Seven (8.0%) patients suffered interstitial lung disease (ILD), including 2 (2.3%) grade 3. T‐DXd showed substantial and durable overall and intracranial efficacy in HER2‐positive and low/zero BCBM, including challenging subgroups with active BM or LMD.

Background: Muscle wasting and sarcopenia in advanced breast cancer correlates with poor outcomes. The serum creatinine-to-cystatin C ratio (CCR) is a potential muscle mass biomarker, but its prognostic value in advanced breast cancer is unclear. Methods: This multicenter retrospective cohort study included 465 patients with stage III-IV breast cancer (2018–2023) receiving standard treatment. The creatinine-cystatin C ratio (CCR) was calculated based on baseline serum markers. The primary endpoint was the 1-year all-cause mortality rate, as assessed through medical records and follow-up. A multivariate Cox regression model was used to analyze the relationship between CCR and mortality, along with restricted cubic spline, Kaplan–Meier survival analysis, ROC curve, and subgroup analysis. Results: This study enrolled a total of 465 patients with stage III-IV breast cancer, with a median age of 52.0 (interquartile range [IQR], 47.0–60.0)years and a median creatinine-cystatin C ratio (CCR) of 1.0 (IQR, 0.8–1.2). The 1-year mortality rate among all patients was 26.2% (122/465), with a mortality rate of 18.1% (52/288) for stage III patients and 39.5% (70/177) for stage IV patients. Multivariate Cox proportional hazards regression analysis showed a significant negative association between CCR and 1-year all-cause mortality in breast cancer patients (adjusted HR = 0.68, 95% CI: 0.63–0.74, p < 0.001). Compared with the lowest quartile group (Q1), the highest quartile group (Q4) had a mortality risk reduction of 94% (HR = 0.06, 95% CI: 0.03–0.14, p < 0.001). Restricted cubic spline analysis confirmed a linear negative association between the two (P for non-linear = 0.178). The Kaplan–Meier survival curves showed a significantly higher 1-year all-cause mortality in the Q1 group ( p < 0.0001). The area under the curve (AUC) for predicting 1-year mortality was 0.802 (95% CI: 0.756–0.849). Subgroup analysis revealed a significant interaction between CCR and chemotherapy ( p = 0.013) and clinical stage ( p < 0.001), while the negative correlation persisted in other subgroups. Sensitivity analysis using unadjusted data yielded consistent results (Q4 HR = 0.06, 95% CI: 0.02–0.14), confirming the robustness of the study conclusions. Conclusion: The serum creatinine-cystatin C ratio is an independent predictor of 1-year mortality risk in advanced breast cancer, with higher levels associated with significantly reduced mortality.