To investigate the expression characteristics of the endoplasmic reticulum stress-related protein Derlin-1 in cervical cancer tissue and its relationship with cervical intraepithelial neoplasia (CIN) tissue, high-risk HPV infection and clinicopathological characteristics, and analyze the potential role of Derlin-1 in the development of cervical cancer and its possible value as a prognostic biomarker. From March 2021 to March 2024, 49 patients with cervical cancer, 40 patients with CINII III, and 30 patients with normal cervical tissue undergoing total hysterectomy due to uterine fibroids were collected. Hematoxylin and eosin (HE) staining was used to observe the histopathological morphology, and immunohistochemical SABC method was used to detect the expression level of Derlin-1 in each group of tissues, and its correlation with the patient’s clinical pathological characteristics (age, FIGO stage, degree of differentiation, lymph node metastasis, vascular tumor thrombus, pathological type) and high-risk HPV infection status was analyzed. The experimental data were statistically analyzed using χ² test and Fisher’s exact probability method. Derlin-1 was mainly localized in the cytoplasm and showed brownish-yellow granular staining. The positive expression rates of Derlin-1 in cervical cancer tissue, CIN tissue and normal cervical tissue were 55.1
The insulin-like growth factor/insulin-like growth factor 1 receptor (IGF/IGF-1R) signaling pathway plays a pivotal role in physiological processes such as cell growth, differentiation, and apoptosis, and its aberrant activation is closely associated with tumor initiation and progression. This review systematically summarizes the molecular mechanisms of the IGF/IGF-1R signaling pathway, its role in tumor metabolic reprogramming and immune microenvironment remodeling, and targeted therapeutic strategies against this pathway, while also exploring future research directions. Through a comprehensive analysis of the available evidence, we propose that IGF/IGF-1R signaling may function as an important regulatory node within a broader metabolic–immune network in cancer. Its effects on tumor metabolism and immune regulation appear to be highly context dependent, varying according to tumor type, cellular state, nutrient availability, and the activation of parallel signaling pathways. Although substantial preclinical evidence supports interactions between IGF/IGF-1R signaling, metabolic reprogramming, and immune regulation, the strength of evidence differs across individual mechanisms, and several proposed feedback relationships remain incompletely validated. Accordingly, biomarker-guided patient selection and mechanism-based combination strategies may provide potential therapeutic opportunities, but their clinical benefit requires further prospective validation.
FAM136A, as a family with sequence similarity 136 member A, is involved in the occurrence and development of some tumors. However, the function of FAM136A in skin cutaneous melanoma(SKCM) is rarely known. We used TCGA, GTEx, and GEO databases to compare differential expression of FAM136A in SKCM and normal tissues. We performed immunohistochemistry(IHC) to study the protein expression of FAM136A in SKCM. Then we discussed the correlation of FAM136A expression with clinical features. Kaplan-Meier was drawn to study the clinical prognosis of FAM136A in SKCM. Cox regression analyses were performed to determine independent factors influencing overall survival (OS) and disease specific survival (DSS). The correlative analysis between FAM136A and immune cell infiltration was investigated by ssGSEA and ESTIMATE algorithm. The relationship of FAM136A expression with immune checkpoints was studied by Spearman analysis. GSEA was used to evaluate the function of FAM136A in SKCM. The results of TCGA and GTEx database showed that FAM136A had higher expression in SKCM than in normal tissues. GEO database had a similar result. IHC results suggested that FAM136A protein expression had higher in SKCM than normal tissues. High expression of FAM136A showed lower OS and DSS in SKCM, and FAM136A had independent influence on OS and DSS in SKCM. FAM136A expression was positively related to Th2, T helper cells, Tcm and Tgd. The stromalscore, immunescore, and estimatescore were higher in low FAM136A expression than in high FAM136A expression. FAM136A expression was positively related to some immune checkpoints, especially PDCD1(PD-1). GSEA results showed that FAM136A-related genes were partook the cell cycle, homologous recombination, basal transcription factors, DNA replication, mismatch repair, and the TGF-β signaling pathway. FAM136A overexpression in SKCM independently predicts poor OS and DSS and is closely associated with immune cell infiltration and PDCD1 expression, highlighting its potential as a prognostic biomarker and immunotherapeutic target.
Diagnosis-based survival estimates become progressively less representative as patients survive beyond the early high-risk period. We characterized conditional overall survival (OS) and cancer-specific survival (CSS) in primary chondrosarcoma and developed interpretable models for conventional and time-updated prediction. Eligible patients diagnosed during 2004–2023 were identified in the Surveillance, Epidemiology, and End Results (SEER) 17 Registries. Conditional survival was calculated as S(x + y)/S(x), and the cohort was divided 7:3 into training and internal testing cohorts. Cox regression, random survival forest (RSF), and CoxBoost were evaluated as feature-selection and survival-modeling methods in nine combinations. The nine combinations were assessed using the C-index, IBS, and time-dependent AUC. The selected Cox models were evaluated by calibration, decision-curve analysis, and comparison with a TNM-only Cox model. Among 2,442 patients, 669 died from any cause and 509 died from chondrosarcoma. Five-year OS and CSS at diagnosis were 76.0
Non-small cell lung cancer (NSCLC) exhibits marked molecular, metabolic, and immune heterogeneity, and treatment pressure further reshapes these states during the development of resistance. N6-methyladenosine (m6A) modification provides a dynamic post-transcriptional layer that controls RNA stability, translation, degradation, and processing, thereby influencing pathways involved in ferroptosis and tumor–immune interactions. Ferroptotic susceptibility is likewise state dependent and reflects the balance among redox-active iron, membrane lipid composition, and partially compensatory antioxidant systems. Emerging evidence indicates that these processes converge in lung cancer: m6A-dependent RNA regulation can alter cystine metabolism, GPX4-centered and GPX4-independent defenses, iron handling, and lipid remodeling, while ferroptotic stress can reciprocally modify checkpoint signaling, myeloid and stromal states, and CD8⁺ T-cell function. Importantly, these effects are compartment specific, because ferroptosis in malignant cells may enhance tumor control whereas ferroptotic injury in immune cells can impair antitumor immunity. Most current studies establish pairwise relationships among m6A regulation, ferroptosis, and immune remodeling, although a smaller number directly connect all three processes within the same experimental context. This review integrates these mechanistic layers, distinguishes causal evidence from association-based signatures, and examines how genotype and treatment history shape their interaction. We further discuss emerging therapeutic opportunities and the methodological and biomarker advances required to translate this framework into state-specific and biomarker-guided treatment strategies for NSCLC.
