Thoracic lymph nodes are critical targets in radiotherapy for locally advanced non-small cell lung cancer (LA-NSCLC), but their accurate localization is complicated by interfractional shifts.

Malignant peripheral nerve sheath tumors (MPNSTs) are rare soft tissue sarcomas with a high risk of recurrence and a poor prognosis, and there is a lack of knowledge regarding long-term follow-up and response to oncological treatment.

To report the initial clinical experience with the radixact synchrony lung with respiratory (LWR) technique in stereotactic body radiotherapy (SBRT) for lung tumors, focusing on feasibility, dosimetric performance, and early clinical outcomes using both standard and extended fractionation regimens.

Chronic obstructive pulmonary disease (COPD) and lung cancer are highly correlated and frequently co-occur. Any degree of COPD significantly increases the risk of developing lung cancer, suggesting they may share common pathogenic mechanisms. The hypoxia-inducible factor 1 (HIF-1) signaling pathway, a complex regulatory network for cellular sensing and response to hypoxia, is abnormally activated in both COPD and lung cancer. Chronic inflammation, immune microenvironment imbalance, extracellular matrix remodeling, epithelial-mesenchymal transition, angiogenesis, and epithelial differentiation, all closely related to the HIF-1 pathway, lie at the intersection of both diseases. Consequently, the HIF-1 pathway is proposed as a potential molecular mechanism underpinning the occurrence, progression, and poor prognosis of lung cancer with COPD (LC-COPD). In this review, we focus on the role and mechanisms of HIF-1 in advancing LC-COPD, highlighting its promising potential as a therapeutic target.

Spread through air spaces has been defined by the WHO as a new pattern of invasion in non-small cell lung cancer (NSCLC). The possible role of surgical manipulation in generating this pattern has recently been discussed. The aim of this study is to review the presence of STAS in patients with lung cancer undergoing video-assisted thoracic surgery (VATS) compared to robotic surgery (RATS). 248 resectable stage I-II adenocarcinoma and squamous cell carcinoma who underwent either VATS or RATS between January 2022 and March 2024 were included. We evaluated the association between STAS and the surgical technique, tumour histology and pathological staging. STAS was found in 45 (29%) of the 157 VATS patients and in 14 (15%) of RATS patients. VATS group showed a higher incidence of STAS (p = 0.020). Both groups presented similar proportions in tumor histology and adenocarcinoma grading. In the RATS group, there were significantly more high-grade adenocarcinomas in those with STAS. Based on a multivariable model, the VATS group had twice the chance to show STAS than the RATS group ((OR 2.24 (1.15, 4.59)). Our findings suggest that mechanical tissue manipulation is a factor involved in the occurrence of STAS. Robotic surgery is associated with a lower rate of STAS in early-stage adenocarcinoma and squamous cell carcinoma.

Head and neck squamous cell carcinoma (HNSCC), the seventh most common cancer globally, has not yet seen an exploration of the specific role of hsa-miR-103a-3p. This study employs integrated bioinformatics analysis to investigate the function, regulatory patterns, and prognostic significance of hsa-miR-103a-3p in HNSCC. The Kaplan-Meier database was used for pan-cancer prognostic analysis of hsa-miR-103a-3p. Expression significance was assessed using the dbDEMC and GSE124566 dataset from GEO. TargetScan, RNA22, miRDB, and miRWalk identified potential targets, while GEPIA 2.0 provided differentially expressed genes (DEGs). Functional and pathway enrichment analyses were conducted using ShinyGO and KOBAS. Elevated hsa-miR-103a-3p expression correlated with poor overall survival and was upregulated in HNSCC tissues. Integration of four target prediction tools yielded 297 candidate genes. Among them, HOXD10, HMGA2, and THY1 showed the highest expression, whereas UBL3, AMOT, and PDK4 displayed low levels. UBE2Q1, ZFPM2, and ATXN1 demonstrated the strongest accessibility to hsa-miR-103a-3p binding. Network analysis revealed interactions with transcription factors and tumor-related genes, while enrichment highlighted involvement in upstream regulators and downstream cancer-associated pathways. This study identified 297 target genes and clarified the regulatory role of hsa-miR-103a-3p through interaction networks, transcription factor associations, and pathway enrichment. These findings suggest a potential oncogenic role for hsa-miR-103a-3p in modulating the cAMP signaling pathway, proteoglycans in cancer, and related mechanisms, thereby linking its molecular regulation to poor prognosis and potential therapeutic targeting in HNSCC.

Gastric cancer (GC) is a prevalent gastrointestinal malignancy in China. Despite advancements in multidisciplinary diagnosis and treatment strategies, the 5-year survival rate remains low at just 10-20%. A significant number of patients ultimately die from postoperative recurrence and distant metastasis. Therefore, it is crucial to investigate the core mechanisms underlying GC development and progression and to identify potential molecular targets for early diagnosis, prevention, and treatment. MAGEA11, part of the melanoma-associated antigen (MAGE) gene family, is associated with several cancers. However, its expression, function, and mechanisms in GC remain unclear. In this study, we first confirmed that MAGEA11 is highly expressed in GC through data analysis from The Cancer Genome Atlas (TCGA), univariate and multivariate Cox regression analyses, and Kaplan-Meier survival curve analysis. Our findings indicate that MAGEA11 is an independent prognostic factor for overall survival (OS) in GC patients, with higher expression levels correlating with shorter OS, disease-specific survival (DSS), disease-free interval (DFI), and progression-free interval (PFI). Next, we explored the role of MAGEA11 in GC by constructing stable cell models with MAGEA11 knockdown and overexpression. Functional assays on these models demonstrated that MAGEA11 promotes the proliferation, migration, and invasion of GC cells in vitro. Additionally, the tumor-promoting effects of MAGEA11 were verified in vivo using a GC cell tumor model. Previous studies have shown that MAGEA11 increases the transcriptional activity of the transcription factor E2F1, thereby promoting cancer progression. To verify this mechanism in GC, we conducted cell function experiments and immunohistochemistry, confirming that MAGEA11 promotes GC development by activating E2F1's transcriptional activity. These findings indicate that MAGEA11 may be a useful molecular marker for predicting GC prognosis.

The location-specific characteristics of superficial esophageal squamous cell carcinoma (ESCC) have not been determined. This study analyzed the locational characteristics of superficial ESCC. Medical records of patients with superficial ESCC treated between December 2008 and November 2024 at Pusan National University Yangsan Hospital were retrospectively reviewed. ESCC locations and final pathological results confirmed by surgery or endoscopic resection were compared. A total of 150 patients with 163 superficial ESCCs were analyzed. Lesions were located in in the upper thoracic (n = 16, 9.8%), mid-thoracic (n = 104, 63.8%), and lower thoracic regions (n = 43, 26.4%). Although upper thoracic lesions had higher deep submucosal cancer (62.5% vs. 29.8%, p = 0.015) and poorly differentiated carcinoma (37.4% vs. 9.6%, p = 0.005) rates than mid-thoracic lesions, no lymph node metastasis or lympho-vascular invasion was detected. In contrast, the deep submucosal cancer rate was less for lower thoracic lesions than mid-thoracic lesions (14.0% vs. 29.8%, p = 0.049), but lymph node metastasis (7.0% vs. 5.8%, p = 0.782) and lympho-vascular invasion (7.0% vs. 4.8%, p = 0.600) rates tended to be higher. Superficial ESCCs in the upper thoracic region had more features requiring surgery but had less lymph node metastasis or lympho-vascular invasion, whereas lesions in the lower thoracic region showed the opposite trend. The results of our study may be helpful when deciding between surgery and endoscopic resection for some patients with superficial ESCC.

Cholangiocarcinoma (CCA) progression involves dysregulated cell cycle control, but core regulatory networks and their roles in tumor heterogeneity remain elusive. We integrated bulk transcriptomics (TCGA-CHOL and GEO cohorts) and single-cell RNA-seq (GSE138709) to identify survival-related genes (SRGs) driving CCA. Through limma, WGCNA, and PPI analysis, we identified seven SRGs (CDK1, ASPM, CCNB1, KIF2C, TOP2A, BUB1, DLGAP5) enriched in G2/M-phase pathways. Single-cell analysis revealed specific SRG upregulation in malignant epithelial subpopulations (PHGR1-Epi/UBE2C-Epi), with pseudotime trajectories demonstrating dynamically increased SRG expression during dedifferentiation. Functional validation confirmed CCNB1 as a core regulator: siRNA knockdown in HuCCT1/RBE cells significantly suppressed proliferation and clonogenicity. This study is the first to define a G2/M-phase gene module promoting CCA progression and map its single-cell dynamics, highlighting CCNB1 as a therapeutic target. Our results reveal SRGs as a coordinated oncogenic network underlying tumor aggressiveness, providing mechanistic insights for future SRG-targeted therapies.

Could cephalosporin antibiotics, extending beyond their established antimicrobial role, be repurposed as precision anticancer agents and chemosensitizers, particularly against inflammation-driven carcinogenesis? To address this question, this study systematically evaluated the anti-colorectal cancer efficacy of cephalosporins both as monotherapies and in synergistic combinations, elucidating their underlying molecular mechanisms. Employing combinatorial phenotypic screening (viability, cell cycle, apoptosis, colony formation), BALB/c nude mouse xenografts, and omics profiling (RNA-seq, RT-qPCR), we identified conserved anticancer pathways and core regulatory axes. Among 18 evaluated cephalosporins, therapeutic specificity was largely associated exclusively variable side-chain moieties, not the conserved β-lactam core. Cefamandole nafate (CAN) and cefuroxime sodium (CUS) demonstrated potent dual efficacy against colorectal cancer model while enhancing cisplatin chemosensitivity. Building on links to inflammation-driven chemosensitization, CUS synergistically potentiated cisplatin and levofloxacin cytotoxicity in colorectal cancer. This synergy was mechanistically driven by apoptosis induction, cell cycle arrest, significant up-regulation of HMOX1 (80-fold peak in combinations; 40-fold as monotherapy) and DDIT3, coupled with down-regulation of MUC1, CASC19, KRT23, SPNS3, LFNG, HS3ST1, NCOA5, and GJB4. Crucially, we reveal for the first time that CUS significantly up-regulates HMOX1 expression in HCT116 cells in a dose-dependent manner, establishing this ferroptosis regulator as the central effector governing both intrinsic anticancer activity and chemosensitization. This study unveils the translational potential of repurposing cephalosporins for combinatorial precision oncology strategies targeting inflammation-driven cancers.

Symptomatic malignant pleural effusions (MPE) are treated with chemical pleurodesis to prevent recurrence. The serum soluble receptor for advanced glycation end products (sRAGE) has been linked to lung cancer progression but its role in predicting talc pleurodesis failure is unclear. A prospective cohort study was conducted from November 2023 to December 2024, encompassing subjects with confirmed MPE. Pleural fluid samples were collected prior to intercostal drainage (ICD) insertion for the measurement of sRAGE, ADAM10, MMP9, and HMGB1 levels. Participants were monitored for 90-day post-pleurodesis failure, pleural interventions, and survival. Among seventy-three adults (median age 66 [IQR 53-74 years]) with MPE who received pleurodesis, lung adenocarcinoma was the most common. Talc pleurodesis failure (24.7%) was associated with greater pleural fluid output, multiple pleurodesis attempts, longer ICD retention, and lower pH and lymphocyte fraction. Pleural sRAGE and MMP9 levels were significantly diminished (p = 0.0033 and p = 0.029, respectively), whereas HMGB1 levels were substantially elevated (p = 0.019) in the failure cases. Among biomarkers, pleural sRAGE had the most predictive value for talc pleurodesis failure, followed by HMGB1 and MMP9. However, pleural sRAGE and MMP-9 lacked prognostic significance for 90-day mortality. The present study demonstrated that lower pleural sRAGE is a potential predictive biomarker for talc pleurodesis failure despite inferiority to pleural acidity. Imbalance between sRAGE and HMGB1 in MPE may be associated with the underlying mechanism for talc pleurodesis failure.

Clear cell renal cell carcinoma (ccRCC) is the most common subtype of renal cell carcinoma (RCC). Although we have made many achievements in the therapy of RCC with the progress of medicine, the clinical management of metastatic RCC remains a daunting challenge. SWI/SNF chromatin remodeling complex-related genes (SCRGs) are significantly associated with tumor progression and cancer cell evolution in ccRCC. This study aimed to investigate the prognostic significance of SCRGs in ccRCC to elucidate its molecular subtype characteristics. Using 29 known SCRGs, 532 ccRCC patients from the TCGA-KIRC cohort were classified into two subtypes (SCRGcluster A and SCRGcluster B). Patients in SCRGcluster B exhibited a significantly poorer prognosis compared to those in SCRGcluster A. Functional enrichment and immune microenvironment profiles significantly differed between the subtypes, with SCRGcluster B showing higher levels of immune infiltration. Five core genes (TMCC3, TOP2A, EPS8, PIK3R3, KCNK5) were identified through the integration of multiple machine learning approaches and multivariate Cox regression analysis. A novel prognostic model based on these core genes was validated in an external cohort. Additionally, single-cell data analysis revealed the expression patterns of these core genes in ccRCC. In vitro experiments demonstrated that KCNK5 is underexpressed in ccRCC cell lines and tissues, and that its overexpression suppresses malignant phenotypes. Specifically, KCNK5 overexpression significantly inhibited the proliferation, migration, and invasion capabilities of ccRCC cell lines. Although the precise functional mechanisms of these core genes in ccRCC are not yet fully elucidated, this study provides new insights for the treatment of ccRCC.

Chronic obstructive pulmonary disease (COPD) is characterized by chronic inflammation of the respiratory tract and is associated with an increased risk of lung cancer. Non-small cell lung cancer (NSCLC) patients with COPD have been shown to exhibit favorable responses to anti-PD-1/PD-L1 therapy. In the present study, we investigated T cell profiles and functions in the lung tissues of NSCLC patients with or without COPD to provide the rationale for immunotherapy of NSCLC patients with COPD. Abundant PD-1+ and Tim-3+ T cells were detected in the lung tumor tissues of NSCLC patients with COPD. On the other hand, CD103+ tissue-resident memory T (TRM) cells in non-tumor lung tissues were more abundant in NSCLC patients with than in those without COPD. Furthermore, the abundance of CD103+ TRM cells in non-tumor lung tissues correlated with IFN-γ production and COPD-related clinical parameters (pack-years smoking history and the FEV1/FVC ratio). In NSCLC patients with COPD, T cells were active participants in both the non-tumor and the lung tumor tissues, suggesting the potential response to immunotherapy.

The PEST-containing nuclear protein (PCNP) has been reported to play paradoxical roles in tumorigenesis. While PCNP functions as a tumor suppressor in neuroblastoma and lung adenocarcinoma, it has been identified as a tumor promoter in ovarian cancer. However, the underlying mechanisms driving these contrasting effects remain unclear. Gene Expression Profiling Interactive Analysis (GEPIA) was employed to analyze relevance of PCNP expression with prognosis in HCC. To evaluate the role of PCNP in hepatocellular carcinoma (HCC), we analyzed the expression of PCNP in 87 HCC tissues and 80 adjacent normal tissues. Correlation between PCNP and ubiquitin-like with PHD and ring finger domains 2 (UHRF2) was transcriptionally detected, and then their effects on malignant behaviors, including proliferation, invasion, tumor formation in vitro and in vivo were evaluated. According to tissues array results, it is found that PCNP was significantly upregulated in HCC tissues, which was further confirmed in HCC cell lines by western blotting. Importantly, both the cytoplasmic and nuclear PCNP fractions were correlated with pathological grade, T staging, clinical staging and recurrence, and patients with a high level of PCNP had lower overall survival and disease-free survival and a higher recurrence rate than those with a low PCNP level, indicating that PCNP might be an independent prognostic factor for HCC patients. Functional investigations revealed that PCNP knockdown inhibited malignant behaviors, including proliferation, invasion, colony formation and tumor formation, in vitro and in vivo. Pearson correlation analysis indicated a positive association between PCNP and UHRF2, with evidence that PCNP transcriptionally upregulates UHRF2. Furthermore, ectopic overexpression of PCNP activated the ErbB3/Ras/Raf1 signaling pathway through upregulation of UHRF2. Our findings suggest that PCNP promotes HCC progression by activating the ErbB3/Ras/Raf signaling pathway through upregulation of UHRF2. Consequently, PCNP holds potential as both a diagnostic biomarker and a therapeutic target for hepatocellular carcinoma.

Endometriosis (EMS) is a chronic gynecological condition affecting 6-10% of reproductive-age women. These lesions, albeit of benign nature, present cancer-like features, and may progress to epithelial ovarian cancer (EOC) through a multistep process. The coexistence of EMS and EOC in the presence of transitional lesions (TL) - i.e. atypical EMS/borderline lesions - is termed as endometriosis-correlated ovarian cancer (ECOC). Given the regulatory role of miRNAs in gene expression and biological pathways, we aimed to identify miRNAs that may drive or modulate the malignant transformation of ovarian EMS. Global miRNA profiling was evaluated on 81 samples (EMS, TL and ECOC) from 44 patients. Principal component analysis and unsupervised clustering revealed two distinct clusters formed by ECOC and ovarian EMS samples, whereas TL were dispersed among the other two. Differential expression analysis (DEA) of TL vs. ovarian EMS, revealed 30 significantly upregulated miRNAs. Comparison of ECOC vs. TL samples yielded 118 significantly upregulated and 77 downregulated miRNAs. Finally, DEA of ECOC vs. ovarian EMS lesions yielded 200 upregulated and 128 downregulated miRNAs. Evaluation of miRNAs commonly deregulated between the three groups showed 14 shared upregulated miRNAs (miR-429, miR-425-5p, miR-200c-3p, miR-200c-5p, miR-200b-3p, miR-200a-3p, miR-183-5p, miR-182-5p, miR-141-5p, miR-141-3p, miR-96-5p, miR-93-5p, miR-10a-5p, miR-10a-3p) with a progressive increase in expression levels, from ovarian EMS to TL and ultimately to ECOC. The identified miRNA expression profiles associated with the progression from ovarian EMS, TL and ECOC provide valuable insights into the molecular progression from benign to malignant lesions and could represent potential biomarkers for the early detection of ECOC.

SEPT9 methylation has been closely linked to breast cancer, yet its role in differentiating disease stages remains unclear. In particular, Few studies previously have examined differences in SEPT9 methylation between ductal carcinoma in situ (DCIS) and invasive ductal carcinoma (IDC), or among DCIS lesions of varying nuclear grades. This study investigated SEPT9 methylation across 105 breast cancer cases, classified into pure DCIS, DCIS with invasive components (DCIS-INV), IDC alone, and metastatic breast cancer (MBC). Methylation levels were measured using real-time PCR, and in vitro experiments were conducted using MCF-7 and T47D cell lines treated with decitabine to explore the relationship between methylation and microtubule stability. SEPT9 methylation was significantly elevated in cancer cells compared to normal breast epithelium, with positivity rates of 90.6% in DCIS-INV, 77.8% in IDC, and 79.2% in MBC, versus only 18.2% in pure DCIS. SEPT9 methylation was negtive in low-grade DCIS and positive in 28.6% of intermediate- to high-grade cases. Positive methylation was significantly associated with high Ki-67 expression and lymph node metastasis (P < 0.05), but showed no correlation with age, menopausal status, tumor size, or hormone receptor status. Additionally, decitabine treatment induced a reduction in SEPT9 methylation levels, which affects microtubule stability, suggesting a potential mechanistic link to tumor invasion. These findings indicate that SEPT9 methylation is a promising biomarker for distinguishing invasive breast cancer from DCIS and for identifying high-risk DCIS lesions with greater potential for progression.

To develop a postoperative recurrence/metastasis risk prediction model for cervical cancer based on circulating tumor cells (CTCs) and tumor fibrosis distance (TFD), and to validate its biological mechanisms through animal experiments. This model aims to guide preoperative risk stratification and personalized treatment strategies. A total of 148 patients with stage IB-IIA cervical cancer who underwent radical surgery between 2020 and 2022 were retrospectively enrolled. Preoperative CTC counts, TFD measurements, and clinicopathological data were collected. Independent prognostic factors were identified using Cox regression analysis. The model's performance was assessed using receiver operating characteristic (ROC) curves, and risk stratification was evaluated with Kaplan-Meier survival analysis. Additionally, an orthotopic tumor model was established in 60 Sprague-Dawley rats divided into six groups (Control, Model, HTFD, LTFD, HCTCs, and LH). Tumor burden, CD4+/CD8 + ratios, IL-6, TNF-α, MDA, and SOD levels were measured to explore the model's underlying metabolic and immune mechanisms. Patients with poor outcomes had significantly higher CTC counts (30.50 vs. 23.74/5 mL, P < 0.001) and lower TFD values (5.47 vs. 5.98 mm, P < 0.001). CTCs ≥ 28/5 mL (OR = 6.63) and TFD ≤ 5.7 mm (OR = 3.37) were identified as independent predictors of poor prognosis. The combined model yielded an AUC of 0.91, with a sensitivity of 90.6%, specificity of 84.5%, and a negative predictive value (NPV) of 94.7%. Patients were stratified into low-, intermediate-, and high-risk groups, with corresponding clinical management recommendations. In high-risk rat groups, elevated CTC release, reduced CD4+/CD8 + ratios, increased IL-6 and TNF-α levels, and significant oxidative damage were observed, supporting the biological plausibility of the clinical model. Unlike conventional models that mainly rely on clinicopathological features, our model incorporates both CTCs and TFD, providing superior discrimination for recurrence risk and offering a novel integrative approach for postoperative surveillance. This dual validation underscores the translational potential of the model, which may be incorporated into individualized postoperative monitoring strategies and multidisciplinary decision-making.

Papillary thyroid carcinoma (PTC) is a malignancy with an ambiguous etiology. The competitive endogenous RNA (ceRNA) hypothesis provides a framework for clarifying the molecular mechanisms that drive carcinogenesis. In this study, we constructed a novel ceRNA network to identify reliable diagnostic and prognostic indicators applicable across all stages of PTC. Transcriptome analysis was performed to identify stage-specific hub genes using the MCC, IVI, and MCODE algorithms. A novel five-layer ceRNA network and its associated regulatory network (DE-TF) were constructed. Receiver operating characteristic curves were used to evaluate the diagnostic performance of elements within both networks. A risk assessment model was developed by identifying key genes from the ceRNA and DE-TF components through univariable Cox regression and LASSO regression analyses. RNA-seq findings were validated by RT-qPCR. The correlations between gene expression levels and blood calcium levels were examined. The ceRNA and DE-TF networks contained 33 and 21 components, respectively. Logistic regression analysis identified PKMYT1, E2F1, NFATC1, STAT6, E2F3, LINC02910, GAS5, and TK1 as reliable diagnostic markers for PTC, achieving an AUC of 96.9%. Among these, PKMYT1 and GAS5 were stage-specific markers, showing significant upregulation in highly aggressive PTC tumors compared to less aggressive ones. Both genes demonstrated strong diagnostic value in differentiating high- from low-aggressive tumors, with AUCs of 0.81 and 0.87, respectively. circMET, which was overexpressed in both low- and high-aggressive tumors, showed diagnostic potential in distinguishing low-aggressive tumors from normal adjacent tissues (AUC = 0.81). GAS5 expression demonstrated an association with blood calcium levels. The SERN prognostic model, including STAT6, E2F1, RMI2, and NR4A1, illustrates the importance of these four genes as reliable prognostic markers for overall survival in PTC. Three components of the ceRNA network-PKMYT1, GAS5, and circMET-were significantly associated with PTC aggressiveness. PKMYT1 and GAS5 demonstrated strong diagnostic value in distinguishing high-aggressive from low-aggressive tumors, while circMET showed notable diagnostic efficacy in differentiating low-aggressive PTC tumors from adjacent normal tissues. Furthermore, GAS5 expression levels were correlated with blood calcium levels.

The prognosis of breast cancer varies by histologic subtype, with infiltrating ductal carcinoma (IDC) being the most prevalent, comprising 70% of infiltrating breast cancers. Long-term survival outcomes for IDC remain unclear, and some non-early-stage IDC patients exhibit better survival than initially expected. Dynamic survival probability offers a more accurate approach to life expectancy estimation compared to traditional methods such as Kaplan-Meier analysis and the tumor-node-metastasis (TNM) staging system-based nomogram (TNM nomogram) .This study aims to develop a conditional survival prediction model for non-early-stage infiltrating ductal carcinoma patients, with a particular focus on long-term survival assessment of female IDC patients at stage IIB and beyond (according to the AJCC classification), to support personalized treatment planning. Female IDC patients from the SEER database (2000-2022) were analyzed. Overall survival probabilities for additional y years after surviving x years were calculated using the Kaplan-Meier method. Lasso, subset regression, and multivariate Cox proportional hazards analysis were applied to identify significant predictors for constructing a conditional survival (CS) nomogram, where CS is defined as the probability of surviving y additional years given that a patient has already survived x years. The CS nomogram was compared to the TNM-nomogram using the concordance index, ROC curves, calibration plots and decision curve analysis (DCA). The conditional survival nomogram, incorporating 12 variables, predicted 3-, 5-, and 10-year survival, as well as 10-year conditional survival. It demonstrated higher predictive accuracy compared to the TNM-nomogram, reflected by a superior concordance index and improved ROC curves. Calibration plots further confirmed its greater precision, and decision curve analysis (DCA) highlighted better net benefits across varying risk thresholds. Unlike the traditional nomogram, which only provides unconditional survival probabilities at diagnosis, the CS-nomogram dynamically updates survival estimates according to the time already survived (CS(y|x) = OS(x + y)/OS(x)). The conditional survival nomogram provides more accurate and personalized survival predictions for non-early-stage IDC patients, surpassing traditional nomogram. This tool offers valuable guidance for clinical decision-making and improves the precision of survival estimations.

Malignant mesothelioma (MM) is a rare, aggressive cancer with poor outcomes due to its heterogeneity and therapy resistance. Patient-derived organoids (PDOs) have emerged as a promising tool for precision medicine, as they faithfully recapitulate key tumor characteristics. This study aimed to establish MM PDOs and develop a PDO-T cell co-culture system to evaluate their utility in guiding personalized MM treatment. MM PDOs were generated from malignant ascites, pleural effusions, fine-needle biopsies, and surgical tissues. Organoids were characterized using H&E staining, immunohistochemistry (IHC), and next-generation sequencing (NGS). PBMC-derived T cells were co-cultured with PDOs to assess immunotherapy and chemotherapy responses. Drug sensitivity testing was performed to evaluate treatment efficacy. 11 MM PDOs were successfully established, which recapitulated the histological features and genomic profiles of their parental tumors. Drug sensitivity testing revealed heterogeneous responses of PDOs, with sensitivity to anlotinib but resistance to cisplatin plus pemetrexed plus bevacizumab. Notably, PDOs established from the same patient at different time points displayed dynamic changes in genetic profiles and drug sensitivities, mirroring in vivo tumor progression. In the PDO-T cell co-culture system, anti-PD-1 immunotherapy, especially combined with chemotherapy, significantly reduced organoids viability of patient PM002. MM PDOs and the PDO-T cell co-culture system constitute robust models for investigating tumor progression, drug responses, and immunotherapy efficacy. These tools highlight their potential in advancing personalized medicine for MM.