Cancer Innovation最新文献

Background

Breast cancer (BC) remains a significant global public health challenge, and its incidence and mortality rates among adolescents and young adults (AYAs) aged 15–39 years are increasing. Compared with older adults, AYAs often face poorer prognoses and a higher disease burden. Understanding the trends and determinants of BC burden in AYAs is crucial for guiding preventive measures, early detection programs, and treatment strategies. The aim of this study is to systematically investigate the trends and distribution of the BC burden among AYAs aged 15–39 years across regions and countries and identify the contributing risk factors and disparities in incidence, mortality, and disability-adjusted life years (DALYs).

Methods

Data on BC were collected from the Global Burden of Disease (GBD) 2021 database. The number of cases, age-standardized rates, mortality, and DALYs for BC were assessed for 204 countries and territories from 1990 to 2021. Joinpoint regression analysis was used to calculate the average annual percentage changes (AAPCs) in incidence, mortality, and DALYs. Risk factors that contribute to the BC burden were also evaluated.

Results

According to GBD 2021 estimates, 180,791 new BC cases and 42,055 related deaths were observed among AYAs globally. Between 1990 and 2021, the global incidence rate increased by 33.4%, with the highest incidence observed in regions with a high sociodemographic index (SDI) and the highest mortality rates in low-SDI regions. Incidence rates in women showed a significant upward trend (AAPC, 3.03) and peaked in North Africa and the Middle East, whereas the most rapid increase in incidence in men was noted in East Asia (AAPC, 4.87). Projections indicated a decline in age-standardized incidence rates across most European countries by 2050, in contrast to rising trends in Asia and Africa. Risk factor analysis identified dietary risks (10.5%), tobacco smoking (2%), and high fasting plasma glucose (1.6%) as major contributors to DALYs.

Conclusions

The global burden of AYA BC has increased significantly, particularly in regions with a middle and low SDI. The findings highlight the need for targeted preventive interventions for high-risk populations and provide critical insights for developing regional control strategies.

Background

To assess whether changes in TP53 mutations and copy number alterations (CNA) in plasma circulating tumor DNA (ctDNA) can predict treatment response and prognosis in platinum-resistant recurrent ovarian cancer (PROC) patients.

Methods

Fifty-seven PROC patients were recruited. Forty-three patients with matched tumor and plasma samples were analyzed via both a tumor-informed ctDNA assay (TICA) and a tumor-uninformed ctDNA assay (TUCA) profiling TP53 mutations and CNA. The TUCA algorithm was optimized based on TICA results. Fourteen patients without matched tumor tissues were used just for TUCA analysis.

Results

A ctDNA decrease of ≥ 80% from baseline or ctDNA negativity during treatment detected by the TICA (defined as favorable TICA changes) strategy before the third cycle predicted the best overall response, with 81.8% sensitivity and 84.6% specificity. The TUCA strategy was defined as a combination of TP53 mutations and CNA changes. A favorable TUCA change before the third cycle predicted the best overall response, with 90.0% sensitivity and 63.2% specificity. In 12 patients without clinical benefit, the median lead time to detect drug resistance from TUCA to the Response Evaluation Criteria in Solid Tumors was 86.0 days. Patients with favorable ctDNA changes (n = 15) detected by TUCA before the third cycle had a median progression-free survival of 9.2 months, versus 3.6 months in those without (n = 34) (HR: 2.88; 95% CI 1.56–5.30; log-rank p = 0.0008).

Conclusions

Similar to TICA, ctDNA changes detected by TUCA combined with TP53 mutations and CNA could predict treatment response and prognosis in PROC patients without requiring tumor tissues.

Background

Ovarian cancer patients with elevated serum CA125 levels after operation have a high incidence of relapse or metastasis. ¹⁸F-FDG PET/CT is an effective imaging method for identifying recurrent or metastatic lesions. This study systematically investigated the diagnostic value of ¹⁸F-FDG PET/CT in this patient population.

Methods

A systematic search of PubMed, Embase, Cochrane Library (Central), Web of Science (SCI-Expanded), and Chinese databases (CNKI, VIP database, Wan Fang Data, CBM) was performed. Studies that evaluated the diagnostic value of ¹⁸F-FDG PET/CT for relapse or dissemination in postoperative ovarian cancer patients with elevated serum CA125 levels were included. The methodological quality of the studies was evaluated using the Quality Assessment of Diagnostic Accuracy Studies 2 tool. Data were analyzed for heterogeneity using Meta-Disc 1.4 software. Sensitivity analysis and release bias evaluation were conducted using STATA 14.0 software.

Thirteen studies (including 421 female patients) qualified for the meta-analysis. The pooled sensitivity and specificity of ¹⁸F-FDG PET/CT were 0.94 (95% CI: 0.91–0.97) and 0.83 (95% CI: 0.71–0.91), respectively. The pooled positive likelihood proportion was 4.59 (95% CI: 2.81–7.51), the pooled negative likelihood proportion was 0.09 (95% CI: 0.05–0.15), and the pooled diagnostic odds ratio was 64.22 (95% CI: 27.21–151.57). The area under the curve was 0.9379. A sensitivity analysis and publication bias test indicated that the outcomes were steady, and there was no reporting bias.

Conclusions

¹⁸F-FDG PET/CT has high diagnostic veracity for identifying recurrence or metastasis in ovarian cancer cases with increased serum CA125 levels after surgery. It can accurately detect recurrent or metastatic lesions, providing valuable information for clinical decision-making.

Background

Breast cancer is a highly heterogeneous disease, characterized by tumor and nontumor cells at various cell states. Ecotyper is an innovative machine learning framework that quantifies the tumor microenvironment and delineates the tumor ecosystem, demonstrating clinical significance. However, further validation is needed in breast cancer.

Methods

Ecotyper was applied to identify multiple cellular states and tumor ecotypes using large-scale breast cancer bulk sequencing data, followed by a detailed analysis of their associations with clinical classification, molecular subtypes, survival prognosis, and immunotherapy response. Identified subtypes were further characterized using single-cell and spatial data sets to reveal molecular profiles.

Results

In a comprehensive analysis of 6578 breast cancer samples from four data sets, Ecotyper identified 69 cellular states and 10 tumor ecotypes. Of these, 37 cellular states significantly correlated with overall survival. Notably, specific states within epithelial cells, macrophages/monocytes, and fibroblasts were linked to a worse prognosis. CE2 abundance was identified as the most significant marker indicating unfavorable prognosis and was further validated in an additional data set of 116 HER2-negative patients. These biomarkers also indicated the efficacy of neoadjuvant immunotherapy in breast cancer. CE2-high cancers were characterized by an abundance of basal-like epithelial cells, scant lymphocytic infiltration, and activation of hypoxia signaling. Single-cell analysis showed that CE2-high areas were rich in SPP1-positive tumor-associated macrophages(TAM), basal-like epithelial cells, and hypoxic cancer-associated fibroblasts(CAF). Spatially, these regions were often peripheral in triple-negative breast cancer, adjacent to fibrotic/necrotic zones. Multiplex immunofluorescence confirmed the enrichment of SPP1+CD68+TAM and HIF1A+SMA+CAF in hypoxic triple-negative breast cancer (TNBC) regions.

Conclusions

Ecotyper identified novel biomarkers for breast cancer prognosis and treatment prediction. The CE2-high region may represent a hypoxic immune-suppressive niche.

Background

Bladder cancer is a common malignancy of the genitourinary system. Recent studies have confirmed the existence of microorganisms in urine. This study aimed to characterize changes in the urinary microbiota of Chinese bladder cancer patients and determine differences between patients with muscle-invasive bladder cancer (MIBC) and those with non-muscle-invasive bladder cancer (NMIBC).

Methods

Urine samples were collected from 64 patients with bladder cancer and 94 disease-free controls using the clean catch method and sequenced by 16S rRNA gene sequencing. Sequencing reads were filtered by VSEARCH and clustered by UPARSE.

Results

Significant associations were found between urinary microbiota and factors such as sex, age, and disease status. After age adjustment, differences in beta diversity were observed between healthy men and women, cancer patients and healthy controls, and NMIBC and MIBC patients. The cancer patients had an increased abundance of 14 bacterial genera, including Stenotrophomonas, Propionibacterium, and Acinetobacter. Notably, Peptoniphilus spp. were enriched in high-risk MIBC patients, indicating their potential as a risk marker. Functional prediction via PICRUSt analysis suggested enriched metabolic pathways in specific disease groups. Furthermore, molecular ecological network analysis revealed differences based on sex and disease type.

Conclusions

This significant microbial diversity indicates a potential correlation between urinary microbiota dysbiosis and bladder cancer, with implications for risk stratification and disease management. The identified urinary microbiota may serve as noninvasive markers for bladder cancer, warranting further validation in larger cohorts. This study provides a foundation for further research on the mechanisms of bladder cancer progression.

Background

Pancreatic adenocarcinoma (PAAD) represents a highly fatal form of cancer. The 5-year survival rate for patients with this disease is only around 10%. A significant hurdle in its management is the absence of characteristic early-stage symptoms. As a result, a large majority of pancreatic cancer patients are diagnosed when the disease has reached an advanced stage or has metastasized. Consequently, taking measures to suppress the occurrence of metastasis in pancreatic cancer can bring about a substantial improvement in patients' survival rates and overall prognosis. SKIL, known to promote cancer progression, is implicated in cell proliferation, epithelial–mesenchymal transition (EMT), and metastasis, but its specific function in pancreatic cancer remains unclear.

Methods

We investigated the effects of SKIL on the proliferation, apoptosis, and metastasis of pancreatic cancer cells. Through ChIP-seq, we identified the SKIL downstream target gene and further explored the mechanism by which SKIL regulates the metastasis of pancreatic cancer cells through functional experiments and Western blot.

Results

A high level of SKIL expression is associated with an unfavorable prognosis in PAAD; it promotes cell migration and EMT. Through ChIP-seq analysis, we identified that SKIL inhibits TSPYL2, a nuclear protein regulating the TGF-β pathway by binding to the TGFB1 promoter. Further studies carried out by us confirmed that SKIL modulates the TGF-β pathway via TSPYL2, facilitating EMT and metastasis in pancreatic cancer cells, independent of Smad4.

Conclusions

These findings reveal a novel regulatory mechanism involving SKIL, TSPYL2, and the TGF-β pathway, offering new therapeutic targets for PAAD.

Background

The phosphoinositide 3-kinase (PI3K)/protein kinase B (PKB or AKT)/mammalian target of rapamycin (mTOR) signaling pathway (PAM pathway) plays a critical role in breast cancer pathogenesis and progression, and is closely linked with resistance to endocrine therapy in advanced breast cancer. Randomized clinical trials have shown that PI3K/AKT/mTOR inhibitors deliver significant clinical benefits, particularly for patients with advanced hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative breast cancer.

Methods

In 2022, the Breast Cancer Expert Committee of the National Cancer Quality Control Center convened specialists in related fields to draft the “Expert Consensus on the Clinical Application of PI3K/AKT/mTOR Inhibitors in the Treatment of Advanced Breast Cancer.” This consensus raised awareness of these inhibitors among oncologists in China and improved the precision of clinical decision-making. In recent years, growing evidence has emphasized the importance of targeting the PAM pathway, reflected in the approval of several innovative agents. This consensus is an updated 2025 edition that retains the foundational structure of the 2022 edition while incorporating notable updates.

Results

Updates to the consensus include the introduction of newly approved PAM pathway inhibitors, updated data from recent clinical trials, and expanded therapeutic applications. The revised guidance also offers updated recommendations for genetic testing to detect alterations in relevant pathways. The section on managing drug-related adverse events has been significantly expanded, providing detailed insights into different types of adverse events and their management. These updates aim to enhance the clinical application of PAM pathway inhibitors, promote precision medicine, and ultimately, improve survival outcomes for patients with breast cancer.

Background

Tuberculosis (TB) and lung cancer (LC) are both major global health threats. However, coexistent pulmonary TB and LC (TBLC) is a unique condition for which incidence trends and risk factors have not been fully defined.

Methods

We retrospectively reviewed the medical records of patients with TBLC and LC alone between 2010 and 2022 at Beijing Chest Hospital, the standard authority for the diagnosis and treatment of TB and LC in China. The cumulative incidence rate (CIR) of TBLC was calculated as the number of new TBLC cases/number of LC cases at risk per 100,000 annually. The comparative incidence rate ratio (IRR) was estimated to be the TB incidence in LC patients/TB incidence in the general population. Logistic regression was used to explore risk factors for TBLC.

Results

The CIR of TBLC has rapidly increased each year since 2014 and reached 7027 per 100,000 LC patients in 2022. Patients with LC had a higher risk of developing active TB than the general population (IRR = 25.21, 95% confidence interval [CI]: 21.54–29.89). Medical expenditure per patient was 100.60 thousand yuan for those with TBLC and 105.60 thousand yuan for patients with LC (p = 0.687). Patients with TBLC were older (63.61 ± 10.46 vs. 61.08 ± 10.77, p < 0.001) and had a higher male-to-female ratio (2.82 vs. 1.59, p = 0.044) than those with LC alone. A tendency of earlier disease onset was observed in patients with LC rather than TBLC. A majority (44.92%) of TBLC lesions were located in the upper lobes of the lung and had a higher proportion of squamous cell carcinomas than LC alone (32.24% vs. 27.49%, p = 0.002). TBLC also presented more aggressively, with more lymph node involvement and distant metastases. Multivariate analysis revealed that older age, the male sex, mediastinal lymph node invasion, lung/bone metastases, anemia, hypoalbuminemia, malnutrition, pulmonary fibrosis, and chronic obstructive pulmonary disease were risk factors for active TBLC.

Conclusions

There has been a rise in the incidence of coexistent TBLC and a concomitant increase in its financial burden in China that deserves more awareness and attention.