Journal of Cancer最新文献

Glioblastoma multiforme (GBM), the most aggressive primary brain tumor, is characterized by high recurrence, metabolic plasticity, and complex tumor microenvironmental interactions. The human chitinase and chitinase-like protein family includes five members (CHI3L1, CHI3L2, CHIA, CHID1, and CHIT1) that share conserved chitinase-related domains but exhibit diverse biological functions in immune regulation and tissue remodeling. While chitinase-like proteins are recognized as mesenchymal-associated markers, however, the role of CHID1 in GBM remains largely unexplored. An integrative multi-omics strategy combining TCGA-GBM and CGGA transcriptomic datasets, single-cell RNA sequencing, and enrichment analyses (GSEA, GO, KEGG, and MetaCore) were used to investigate CHID1 expression patterns and associated transcriptional programs. Pharmacogenomic correlations and molecular docking were used to explore potential drug-response associations. CHID1 showed higher expression in GBM compared to the normal brain and was associated with poor overall survival. A single-cell analysis showed tumor-associated expression patterns of CHID1 across malignant samples. Pathway enrichment analyses identified transcriptional programs related to oxidative phosphorylation, redox-related processes, DNA repair, and cell cycle pathways. Collectively, this study provides a comprehensive multi-cohort and multi-modal characterization of CHID1 expression in GBM, integrating bulk transcriptomics, single-cell RNA sequencing, and tissue-level validation. The findings establish CHID1 as a GBM-associated transcriptional marker linked to metabolic and redox-related programs and provide a systematic resource for future investigations into chitinase family-related biology in GBM.

Introduction: Adult-type granulosa cell tumors (AGCTs) are rare ovarian neoplasms with a low overall incidence of recurrence, and also data on secondary recurrence and survival after relapse remain limited. This study aimed to identify factors associated with secondary recurrence and survival after recurrence in patients with recurrent AGCTs.

Methods: This multicenter retrospective study included 52 patients with recurrent AGCTs identified among 484 patients treated between 2000 and 2023. Clinical characteristics, treatment modalities, and outcomes were analyzed, with a particular focus on factors associated with secondary recurrence and survival after first recurrence. Recurrence-free survival and overall survival after first recurrence (OS-FR) were evaluated using Kaplan-Meier analysis.

Results: The mean follow-up duration was 99.2 ± 61.5 months. Secondary recurrence occurred in 17 patients (32.7%). A serum CA-125 level >35 U/mL at the time of first recurrence was significantly associated with an increased risk of secondary recurrence (p=0.01). Factors significantly associated with improved OS-FR included a CA-125 level ≤35 U/mL at initial diagnosis and at first recurrence, absence of residual disease following surgery for the first recurrence, and administration of salvage chemotherapy (all p<0.05). In subgroup analysis, salvage chemotherapy was associated with improved OS-FR in patients with residual disease or those who did not undergo surgery (p < 0.01), but not in patients who achieved complete cytoreduction (p = 0.67).

Conclusions: Secondary recurrence remains a significant clinical challenge in AGCTs. Serum CA-125 levels, surgical outcomes at first recurrence, and the use of salvage chemotherapy may help management strategies in recurrent disease.

Background: Papillary thyroid carcinoma (PTC), the most common thyroid malignancy, shows marked clinical heterogeneity despite generally favorable outcomes. Lysosome-dependent cell death (LDCD), a form of programmed death triggered by lysosomal membrane permeabilization, has emerged as a potential cancer therapy target, but its role in PTC remains unclear.

Methods: Transcriptomic data from public cohorts were analyzed to identify LDCD-related genes (LDCDRG) associated with PTC prognosis. Cox analysis and LASSO regression analyses were performed to construct a prognostic model. Immune landscape, drug sensitivity, and single-cell expression profiles were examined. Functional experiments were conducted in vitro to verify the biological effects of the key gene LMTK3 on PTC cell proliferation, viability, and invasion.

Results: Nineteen LDCDRG were differentially expressed between normal and tumor tissues, defining three molecular subtypes with distinct immune and prognostic profiles. A six-LDCDRG signature (LMTK3, MCM5, NXF1, TUBB4B, LIMCH1 and APH1B) effectively stratified patients into high- and low-risk groups with significantly different survival outcomes and acceptable predictive performance. High-risk patients showed reduced immune infiltration and lower predicted immunotherapy-related immune activity. LMTK3, the highest-risk gene, was highly expressed in PTC cells, and its knockdown suppressed proliferation and invasion in vitro.

Conclusions: The established six-LDCDRG signature provides an exploratory tool for risk stratification and survival prediction, while LMTK3 emerges as potential target worthy of further investigation. These findings deepen our understanding of lysosome-dependent cell death in thyroid carcinogenesis and may provide insights into the development of personalized management strategies and novel treatment approaches for high-risk PTC patients.

Introduction: The ypT staging system has limited prognostic value after neoadjuvant therapy, as it primarily reflects only tumor characteristics alone. This study proposes a novel staging system that integrates circumferential resection margin (CRM) status with the ypT category to enhance prognostic accuracy following neoadjuvant chemoradiotherapy (nCRT) for rectal cancer.

Methods: We analyzed data from 4,308 rectal adenocarcinoma patients treated with nCRT followed by surgery, using the Taiwan Cancer Registry and National Health Insurance Research Database (2011-2021). CRM involvement was defined as a margin ≤1 mm. Overall survival was assessed using multivariable Cox regression, and prognostic performance of the proposed CRM-integrated ypT staging system was compared with the American Joint Committee on Cancer (AJCC) TNM system using Harrell's c-statistic.

Results: CRM involvement (≤1 mm) was significantly associated with worse 5-year survival (adjusted odds ratio, 0.44; 95% CI, 0.31-0.61). Due to the low rate of CRM positivity in ypT0-2 patients, a modified ypT classification was established: new ypT3 (ypT3 and CRM-), new ypT4A (ypT4A and CRM-), new ypT4B (ypT3 and CRM+ or ypT4B and CRM-), and new ypT4C (ypT4A and CRM+ or ypT4B and CRM+). This system demonstrated better prognostic discrimination than the current AJCC classification (Harrell's c-statistic: 0.756 vs. 0.752, P = 0.034).

Conclusions: Incorporating CRM into the ypT stage offers survival stratification and may guide more individualized postoperative treatment strategies for rectal cancer patients after nCRT.

Malignant pleural effusion (MPE) and malignant ascites (MA) are common complications in advanced-stage cancers, often signifying disease progression and resistance to treatment. Compared to tissue biopsies or surgical specimens, materials derived from effusions offer advantages such as minimal invasiveness, ease of accessibility, and the feasibility of repeated collection during therapeutic interventions. Organoids generated from tumor cells in effusions, termed fluid-derived organoids (FDOs), have demonstrated the ability to maintain genetic heterogeneity and accurately replicate patient-specific tumor phenotypes. These characteristics position FDOs as promising models for investigating drug resistance mechanisms and informing personalized oncology strategies. In the context of lung cancer, organoids derived from pleural effusions have been employed to study acquired resistance to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors and immunotherapy. Similarly, in ovarian and gastrointestinal cancers, organoids derived from ascites have proven to be valuable platforms for examining chemotherapy resistance and conducting drug sensitivity testing. FDOs have shown significant potential for translational applications by effectively correlating ex vivo drug responses with clinical outcomes, thus facilitating real-time monitoring of resistance evolution. However, several challenges remain, such as achieving culture standardization, maintaining the integrity of tumor microenvironment components, and integrating with multi-omics approaches. This review provides a comprehensive overview of recent advancements in the use of pleural effusion- and ascites-derived organoids for drug resistance research, underscores their applications in personalized oncology, and explores future research directions.

Background: Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide and its incidence and mortality rates remain high. Therefore, new diagnostic and therapeutic approaches are urgently required. Family with sequence similarity 188 member B (FAM188B) encodes an evolutionarily conserved protein that is highly expressed in various cancers. While FAM188B has been implicated in the progression of several tumors, its role in HCC progression remains unknown.

Methods: We analyzed FAM188B expression in HCC using The Cancer Genome Atlas (TCGA) and The University of Alabama at Birmingham Cancer data analysis Portal (UALCAN) databases. Functional studies included in vitro proliferation, migration, and invasion assays, as well as in vivo xenograft models. Co-immunoprecipitation (Co-IP), Western blotting, and immunofluorescence were used to investigate the FAM188B-Ubiquitin-specific peptidase 10 (USP10)-Yes-associated protein/Transcriptional coactivator with PDZ-binding motif (YAP/TAZ) interaction.

Results: FAM188B was found highly expressed in HCC cells and associated with poor prognosis. Both in vitro and in vivo, FAM188B promoted the proliferation, migration, and invasion of HCC. FAM188B directly interacts with and stabilizes USP10 and the downregulation of FAM188B by shRNA led to decreased USP10 and YAP/TAZ protein levels, suggesting that FAM188B may regulate the YAP/TAZ pathway through its interaction with USP10.

Conclusion: Our findings reveal that FAM188B plays a crucial role in enhancing HCC cell proliferation, migration, and invasion, primarily through regulating the USP10/YAP/TAZ signaling axis, which was validated in vitro and in vivo.

Background: Sarcopenia, defined as a reduction in muscle mass assessed using scales such as the psoas muscle mass index (PMI), is accompanied by decreased muscle strength or physical function. However, sarcopenia's effect in patients with pancreatic cancer (PC) receiving chemotherapy remains unclear. In addition, recent international studies have demonstrated that intramuscular fat infiltration, assessed using parameters such as FRPM, is associated with poor prognosis across various malignancies. However, evidence regarding its prognostic significance in pancreatic cancer remains limited. We aimed to evaluate the relationship between sarcopenia and the prognosis of patients with PC receiving palliative chemotherapy.

Methods: We retrospectively reviewed patients diagnosed with unresectable PC who received gemcitabine plus nab-paclitaxel (GnP) as the first-line therapy at our hospital between 2018 and 2021. We calculated PMI, defined as the sum of the bilateral psoas muscle mass at the lumbar three (L3) level and FRPM, defined as the sum of areas within the psoas muscles corresponding to fat at the L3 level from Vincent® on the CT images. We compared the overall survival (OS) between the PMI-high and PMI-low groups and the FRPM-high and FRPM-low groups.

Results: Of 46 patients, 37 were eligible. Eighteen (49%) and 19 (51 %) patients were classified into PMI-high and PMI-low groups, respectively. Twenty (54%) and 17 patients (46%) were classified into FRPM-high and FRPM-low groups, respectively. The median OS was 16.4 months in PMI-high and 8.7 months in PMI-low groups (hazard ratio [HR]: 0.45, 95% confidence interval [CI]: 0.23-0.90, P < 0.01). The median OS was 15.6 months in FRPM-low and 8.5 months in FRPM-high groups (HR: 0.36, 95% CI: 0.18-0.76, P < 0.01). In multivariate analysis, the presence of ascites (P < 0.01), PMI-low (P = 0.02), and FRPM-high (P = 0.03) were independent adverse prognostic factors for OS.

Conclusion: Muscle-related parameters may be independent indicators of poor prognosis in patients with PC treated with first-line GnPs.

Patients with malignant tumors often experience fluctuations in the severity of their symptoms depending on the time of day. In traditional Chinese medicine, symptoms are said to follow a pattern of "mild in the morning, stable by day, worsening in the evening, and severe at night." This article investigates the circadian chronobiology of symptoms and examines their molecular pathophysiology. Evidence suggests that disruptions in core circadian clock genes, such as BMAL1 and PER, along with the dysregulation of cellular metabolic pathways, immune responses, and endocrine functions, synergistically facilitate tumor growth and metastasis during nocturnal periods. These molecular alterations contribute to symptom exacerbation through mechanisms which include direct tumor invasion, neural infiltration, inflammatory processes, dorsal root ganglion (DRG) sensitization, and abnormal melatonin secretion. The article further explores three chronotherapeutic strategies and assesses melatonin's role in targeted oncological therapy, aiming to optimize circadian regulation and symptom management, thereby providing a scientific foundation for personalized anti-tumor interventions that are based on circadian rhythms.

The proteasome assembly chaperone (PSMG) gene family (comprised of PSMG1, PSMG2, PSMG3, and PSMG4) plays a critical role in proteasome biogenesis; however, its involvement in breast cancer remains poorly understood. Among these chaperones, PSMG3 is uniquely and markedly elevated in breast cancer and is associated with poor clinical outcomes. We systematically investigated the roles of PSMG family genes in breast cancer by integrating multi-cohort genomic and transcriptomic datasets, including TCGA-BRCA, METABRIC, and multiple NCBI GEO cohorts. Comprehensive bioinformatics analyses were performed using bulk RNA sequencing and single-cell RNA sequencing data. A gene set enrichment analysis (GSEA) and immune infiltration analyses (CIBERSORT and TIMER) were applied to characterize dysregulated biological pathways, tumor microenvironmental features, and clinical relevance. In addition, molecular docking analyses were conducted to assess the druggability and binding potential of PSMG family proteins with selected small-molecule inhibitors. Elevated PSMG3 expression was consistently associated with poor survival outcomes across multiple breast cancer cohorts. Functional enrichment analyses revealed that PSMG3-high tumors were characterized by activation of hypoxia-related signaling pathways and dysregulated fatty acid metabolism, suggesting a role for PSMG3 in metabolic reprogramming. Immune deconvolution analyses further demonstrated significant correlations between PSMG3 expression and distinct immune cell populations within the tumor microenvironment. These findings were supported by single-cell transcriptomic profiling, which revealed subtype-specific expression patterns of PSMG3 in malignant epithelial cell populations. This integrative multi-omics analysis identified PSMG3 as a clinically relevant proteasome assembly chaperone associated with aggressive breast cancer phenotypes, metabolic dysregulation, and tumor immune contexture. Collectively, these results highlight PSMG3 as a promising prognostic biomarker and potential therapeutic target in breast cancer.

Hepatocellular carcinoma (HCC) ranks as the fifth supreme prevalent cancer within men globally and the ninth among female, serving as a significant contributor to cancer-associated deaths. The adipokine omentin-1 has been demonstrated to have a defensive effect by decreasing the secretion of proinflammatory cytokines. The connections among lifestyle factors that promote cancer, OMNT1 polymorphisms, and HCC are still not well understood. Our investigation focused on the influence of clinicopathological characteristics and four variants of the OMNT1 gene (rs2274907, rs35779394, rs4656959, and rs79209815) on healthy controls as well as Taiwanese individuals with HCC. According to our data, individuals with the OMNT1 rs79209815 variant (TC or CC genotypes) are at an elevated risk of progressing to stage III/IV disease and larger tumors than those with the TT genotype. Males exhibited these associations more prominently than females. Moreover, OMNT1 expression levels were markedly reduced in individuals with the wild-type TT homozygous genotype when compared to those with the TC or CC genotypes of rs79209815. The complexity of genetic influences on HCC is highlighted by our study, which suggests that OMNT1 polymorphisms may have an impact on tumor stage and progression.