Chinese Journal of Cancer Research最新文献

Pancreatic cancer, particularly pancreatic ductal adenocarcinoma (PDAC), is one of the most lethal malignancies, which is characterized by a complex tumor microenvironment (TME) that fosters immune evasion and treatment resistance. Recent genomic advancements have unveiled diverse molecular subtypes of PDAC, providing insights into targeted therapies and precision medicine. This review synthesizes the current understanding of PDAC's molecular characterization and immunosuppressive TME, as well as emerging therapeutic strategies, including innovative approaches targeting key molecular pathways such as kirsten rat sarcoma viral oncogene homolog (KRAS), epidermal growth factor receptor (EGFR), and immune checkpoints. Despite advances, challenges remain in overcoming treatment resistance and inherent heterogeneity of pancreatic cancer subtypes. We highlight the need for multidisciplinary collaboration to enhance early diagnosis and develop individualized therapeutic protocols, paving the way for improving the outcomes of this aggressive cancer. This integrated perspective underscores the urgency of transforming the innovative research into pancreatic cancer management.

In the past decade, immunotherapies targeting cytotoxic T-lymphocyte antigen-4 (CTLA-4), programmed cell death 1 (PD-1), and PD-1 ligand (PD-L1) have been approved for solid tumors. However, some patients demonstrate suboptimal clinical outcomes due to resistance. The tumor microenvironment (TME) significantly affects the efficiency of immunotherapy by mediating interactions between tumor and non-tumor cells, including dendritic cells, T cells, B cells, macrophages, neutrophils, NK cells, and myeloid-derived suppressor cells (MDSCs). These non-tumor cells often exhibit two phenotypes with altered functions, and tumor cells drives their transition towards tumor promotion through tumor-education. Tumor-educated cells (TECs) are cells influenced by tumor cells, which acquire immune-suppressive phenotypes and promote tumor progression through resistance to anti-cancer therapies. These cells undergo modifications in response to signals from the tumor, which can influence their roles in tumor progression. Their dynamic interactions with tumor cells contribute to the reshaping of the TME, facilitating cancer growth and immune modulation. This review summarizes research on TECs in TME, explores mechanisms related to tumor education, and discusses their role in tumor progression and immunotherapy resistance. Additionally, potential therapeutic approaches targeting these cells are also reviewed, which may complement current treatment strategies.

Objective: This study aimed to describe the updated disease burden and temporal trends of stomach cancer (SC) and colorectal cancer (CRC), and to explore potential influence factors of the two cancers in the Western Pacific region (WPR).

Methods: Estimates of incidence, deaths, and disability-adjusted life years (DALYs) for SC and CRC were obtained from the Global Burden of Disease Study 2021. Trends in age-standardized incidence rates (ASIR), age-standardized mortality rates (ASMR), and age-standardized DALY rates (ASDR) were assessed. A decomposition analysis was conducted to quantify the role of three factors (i.e., population aging, population growth, and epidemiological change) driving DALY changes between 2000 and 2021. Pearson correlation analysis was used to examine the association between cancer burden and Socio-demographic Index (SDI) at the national level in 2021.

Results: In 2021, the WPR accounted for 61.77% of global incident SC cases and 43.07% of global incident CRC cases. From 2000 to 2021, the ASIR, ASMR, and ASDR of SC and the ASMR and ASDR of CRC decreased, whereas the ASIR of CRC increased by an average of 1.32% per year. Among the 31 WPR countries and territories, China had the highest number of incident cases, deaths, and DALYs for both cancers in 2021. Epidemiology change was the primary driver to the reduction of DALYs for SC, while population aging and population growth contributed to the increase of DALYs for CRC. Additionally, ASMR (r=-0.37, P=0.041) and ASDR (r=-0.43, P=0.016) of SC were negatively correlated with SDI in 2021, whereas positive correlations were observed between SDI and ASIR (r=0.74, P<0.001), ASMR (r=0.47, P=0.008), and ASDR (r=0.36, P=0.044) for CRC.

Conclusions: SC and CRC continue to pose considerable public health threats in the WPR. Targeted prevention and control strategies should be prioritized, particularly in high-burden and resource-limited countries.

Objective: The Safety of robotic gastrectomy (RG) compared to laparoscopic gastrectomy (LG) for gastric cancer remains uncertain on a national scale, with limited comparative studies across institutions. This study aims to compare the morbidity rates between RG and LG using data from a nationwide survey.

Methods: We utilized data from the Korean Gastric Cancer Association's 2019 nationwide survey. The proportion of robotic surgeries in minimally invasive surgery at each institution was classified using a cut-off value of 10%, and defined as high robotic proportion cohort and low robotic proportion cohort. We analyzed surgical outcomes between robotic and laparoscopic gastrectomy in each cohort using propensity score matching (PSM). To account for potential clustering effects within hospitals, we employed Generalized Estimating Equations with hospital as the clustering variable.

Results: This study included 776 patients who underwent RG and 7,804 patients who underwent LG for gastric cancer. In low robotic proportion cohort, RG had a longer operation time (P<0.001) but similar blood loss (P=0.792) compared to LG. In the high robotic proportion cohort, RG showed longer operation time (P<0.001), less blood loss (P<0.001), and shorter hospital stays (P<0.001) compared to LG. Additionally, RG in the high robotic proportion cohort had shorter operative time (P<0.001) and less blood loss (P=0.024) compared with that in the low robotic proportion cohort.

Conclusions: RG demonstrated comparable perioperative outcomes to LG in a nationwide PSM analysis. However, RG offers limited benefits over LG at institutions with lower frequencies of RG use.

Objective: A risk-based sequential screening strategy, from questionnaire-based assessment to biomarker measurement and then to endoscopic examination, has the potential to enhance gastric cancer (GC) screening efficiency. We aimed to evaluate the ability of five common stomach-specific serum biomarkers to further enrich high-risk individuals for GC in the questionnaire-identified high-risk population.

Methods: This study was conducted based on a risk-based screening program in Ningxia Hui Autonomous Region, China. We first performed questionnaire assessment involving 23,381 individuals (7,042 outpatients and 16,339 individuals from the community), and those assessed as "high-risk" were then invited to participate in serological assays and endoscopic examinations. The serological biomarker model was derived based on logistic regression, with predictors selected via the Akaike information criterion. Model performance was evaluated by the area under the receiver operating characteristic curve (AUC).

Results: A total of 2,011 participants were ultimately included for analysis. The final serological biomarker model had three predictors, comprising pepsinogen I (PGI), pepsinogen I/II ratio (PGR), and anti-Helicobacter pylori immunoglobulin G (anti-H. pylori IgG) antibodies. This model generated an AUC of 0.733 (95% confidence interval: 0.655-0.812) and demonstrated the best discriminative ability compared with previously developed serological biomarker models. As the risk cut-off value of our model rose, the detection rate increased and the number of endoscopies needed to detect one case decreased.

Conclusions: PGI, PGR, and anti-H. pylori IgG could be jointly used to further enrich high-risk individuals for GC among those selected by questionnaire assessment, providing insight for the development of a multi-stage risk-based sequential strategy for GC screening.

Objective: Pathologic complete response (pCR) following neoadjuvant therapy (NAT) for gastric cancer (GC) is rare but associated with a favorable prognosis. This study aims to reassess the optimal response population (ORP) following NAT by evaluating the prognostic outcomes associated with various T and N stages, utilizing multicenter data from China.

Methods: Patients who underwent NAT following radical gastrectomy at 10 tertiary hospitals in China between 2008 and 2021 were included. The ORP was introduced to explore the disease-free survival (DFS), overall survival (OS), recurrence patterns, and influencing factors following propensity score matching (PSM).

Results: A total of 1,076 patients were enrolled in this study (median follow-up period: 60 months). We defined ORP as a pCR or tumor infiltration of the mucosal or submucosal layer without lymph node metastasis (pCR or ypT1N0) after NAT. The ORP group comprised 136 patients (12.6%), while the non-ORP group comprised 940 patients (87.4%). After applying a 1:4 PSM, we obtained an ORP group of 136 patients and non-ORP group of 544 patients. Survival analysis demonstrated that both the 3-year OS (before PSM: 89.0% vs. 55.0%, P<0.001; after PSM: 89.0% vs. 55.4%, P<0.001) and DFS (before PSM: 85.8% vs. 49.7%, P<0.001; after PSM: 85.8% vs. 50.6%, P<0.001) were significantly superior in the ORP group compared to that in the non-ORP group. Remarkably, adjuvant chemotherapy did not impact the prognosis of patients in the ORP group (3-year OS: 89.0% vs. 89.7%, P=0.988; 3-year DFS: 84.9% vs. 89.7%, P=0.700).

Conclusions: This study reevaluates patients with ORP following NAT, providing a more comprehensive and accurate depiction of the potential beneficiary group and survival outcomes in patients with locally advanced GC.

The intricate interactions between immune cells and tumors exert a profound influence on cancer progression and therapeutic efficacy. Within the tumor microenvironment, exosomes have emerged as pivotal mediators of intercellular communication, with their cargo of non-coding RNAs (ncRNAs) serving as key regulatory elements. This review examines the multifaceted roles of immune cell-derived exosomal ncRNAs in tumor biology. The involvement of various immune cells, including T cells, B cells, natural killer cells, macrophages, neutrophils, and myeloid-derived suppressor cells, in utilizing exosomal ncRNAs to regulate tumor initiation and progression is explored. Additionally, the biogenesis and delivery mechanisms of these immune cell-derived exosomal ncRNAs are discussed, alongside their potential clinical applications in cancer.

Objective: Lymphovascular invasion (LVI) is a crucial step in metastasis and is closely associated with poor prognosis in patients with breast cancer. However, its clinical and molecular characteristics remain insufficiently defined. We aimed to identify molecular targets for LVI-positive (LVI+) breast cancer and predict patient prognosis via the analysis of genomic variations using targeted sequencing.

Methods: We established a large-scale targeted sequencing cohort of 4,079 breast cancer samples, which included 3,159 early-stage and locally advanced patients with available LVI statuses. Comparisons of somatic mutation frequencies and germline pathogenic/likely pathogenic (P/LP) mutation frequencies, mutational signature analyses, and mutual exclusivity and co-occurrence analyses were performed to identify key genomic features involved in LVI+ patients. Additionally, Kaplan-Meier survival analysis was conducted to further explore the prognostic value of co-mutations in LVI+ cases.

Results: We observed that LVI+ patients with the hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-) and triple-negative breast cancer (TNBC) subtypes exhibited worse disease-free survival. Notably, HR+/HER2- and HER2+ breast cancer patients with LVI displayed distinct genomic features compared with LVI- tumors. Specifically, LVI+ HR+/HER2- tumors exhibited greater frequencies of somatic mutations in TP53 and ESR1, germline BRCA2 P/LP variations, and an enrichment of clock-like single-base substitution (SBS)1 mutational signatures. In contrast, LVI+ HER2+ tumors demonstrated a higher incidence of somatic PIK3CA mutations and increased activity of the apolipoprotein B mRNA editing enzyme catalytic polypeptide (APOBEC)-associated SBS2 signature. Furthermore, we revealed that the co-mutation of TP53 and NF1 could serve as a potential prognostic marker for LVI+ HR+/HER2- patients.

Conclusions: Our findings provide a comprehensive overview of the genomic characteristics of LVI in breast cancer, thereby offering insights that may help in refining precision treatment strategies for LVI+ breast cancer patients.

Objective: Radiotherapy (RT) is the definitive treatment for stage II nasopharyngeal carcinoma (NPC), which is classified as stages IA and IB in the latest ninth edition of American Joint Committee on Cancer (AJCC)/Union for International Cancer Control (UICC). A crucial question is whether concurrent chemo-radiotherapy (CCRT) could derive additional benefits to this recent "down-staging" subgroup of NPC patients. This study aimed to interrogate clinical and radiomic features for predicting 5-year progression-free survival (PFS) of stage II NPC treated with RT alone or CCRT.

Methods: Imaging and clinical data of 166 stage II NPC (eighth edition AJCC/UICC) patients were collected. Data were allocated into training, internal testing, and external testing sets. For each case, 851 radiomic features were extracted and 10 clinical features were collected. Radiomic and clinical features most associated with the 5-year PFS were selected separately. A combined model was developed using multivariate logistic regression by integrating selected features and treatment option to predict 5-year PFS. Model performances were evaluated by area under the receiver operating curve (AUC), prediction accuracy, and decision curve analysis. Survival analyses including Kaplan-Meier analysis and Cox regression model were performed for further analysis.

Results: Thirteen radiomic features, three clinical features, and treatment option were considered for model development. The combined model showed higher prognostic performance than using either. For the merged testing set (internal and external testing sets), AUC is 0.76 (combined) vs. 0.56-0.80 (clinical or radiomic alone) and accuracy is 0.75 (combined) vs. 0.62-0.73 (clinical or radiomic alone). Kaplan-Meier analysis using the combined model showed significant discrimination in PFS of the predicted low-risk and high-risk groups in the training and internal testing cohorts (P<0.05).

Conclusions: Integrating with clinical and radiomic features could provide prognostic information on 5-year PFS under either treatment regimen, guiding individualized decisions of chemotherapy based on the predicted treatment outcome.