Chinese Journal of Cancer Research最新文献

Objective: To explore the prognosis-predictive influence of human epidermal growth factor receptor 2 (HER2)-low status in breast cancer patients after neoadjuvant therapy (NAT).

Methods: Consecutive patients with invasive breast cancer who underwent NAT and surgery from January 2009 to December 2020 at multiple centers were included. A modified CPS+EG scoring system that integrates HER2-low status, CPS+EGH_low was developed. Multiple scoring systems were compared via receiver operating characteristic curves with the area under curve (AUC), the Akaike information criterion, the C-index, and calibration curves.

Results: A total of 2,141 patients were included: 1,074, 640, and 427 patients in the training, internal validation, and external validation groups, respectively. HER2-low patients had a significantly better breast cancer-specific survival (BCSS, P=0.008) and recurrence-free interval (RFI, P=0.030) compared to HER2-zero patients (P=0.038) but inferior outcomes than HER2-amplified ones (BCSS, P=0.002; RFI, P<0.001). The CPS+EGH_low (AUC: 0.846, 0.817, 0.901) could stratify patients according to BCSS in training, internal validation, and external validation group, respectively, overperforming pathological stage (PS) (AUC: 0.746, 0.779, 0.754), CPS+EG (AUC: 0.771, 0.752, 0.748), and Neo-Bioscore (AUC: 0.783, 0.777, 0.786, all P<0.05).

Conclusions: HER2-low status showed a significant prognostic value in breast cancer patients after NAT. The CPS+EGH_low model significantly outperformed PS, CPS+EG, and Neo-Bioscore in clinical outcome prediction, which may guide further therapy targeting HER2-low.

Objective: Data on the global, regional and national changes in the trends of colorectal cancer (CRC) are analyzed to understand the trends in its burden, in order to assist policymakers in allocating healthcare resources and developing prevention and control strategies.

Methods: This study analyzed trends in age-standardized incidence rate (ASIR), age-standardized mortality rate (ASMR), and disability-adjusted life years (DALYs) for CRC from 1990 to 2021 using data from the Global Burden of Disease (GBD) 2021 database. The trends of burden and effectiveness of control strategies were assessed using jointpoint regression analysis, decomposition analysis and frontier analysis.

Results: Globally, the ASMR and age-standardized DALYs for CRC have shown a declining trend, but the ASIR was still increasing. The number of new cases of CRC in 2021 was higher in males than in females, the values were 1,263.46 thousands [95% confidence interval (95% CI): 1,146.50, 1,400.38] vs. 930.68 thousands (95% CI: 824.67, 1,017.65). The change in DALYs was mainly due to population growth (111.42%). The high socio-demographic index (SDI) region had an ASIR of 40.52 (95% CI: 37.45, 42.45), and the low SDI region had an ASIR of 7.39 (95% CI: 6.65, 8.19). The ASIR for CRC showed an upward trend in all SDI regions before age of 40 years. Among the four world regions, only America showed a downward trend in ASIR, with an estimated annual percentage change (EAPC) of -0.62 (95% CI: -0.71, -0.53). Among the 204 countries and territories, Netherlands, Monaco, and Bermuda were the top 3 countries with the highest ASIR in 2021. In the frontier analysis of DALYs, the 10 countries with the longest effective distances all had SDI levels above 0.70.

Conclusions: Although ASMR and age-standardized DALYs are declining, ASIR is still increasing globally and in many regions. The burden of CRC varies significantly across the globe, and more targeted screening strategies and prevention measures are needed to address the problem of CRC.

As a key component of tumor microenvironment, the microbiota has gradually played a key role in cancer research. Particularly in colorectal cancer, the specific population of microbiota within the tumor shows a strong association with the tumor type. Although the existence and potential role of microbiota in tumors have been recognized, the specific associations between the microbiota and tumor tissue and the mechanism of action still need to be further explored. This paper reviews the discovery, origin, and emerging role of the intratumor microbiota in the immune microenvironment and systematically outlines the oncogenic and metastasis-promoting strategies of the intratumor microbiota. Moreover, it comprehensively and holistically evaluates therapeutic strategies and prognostic performance on the basis of the intratumor microbiota, with the goal of providing strong support for future research and clinical practice.

Objective: To explore the impact of visceral fat area (VFA) on the short- and long-term efficacy of indocyanine green (ICG)-guided D2 lymphadenectomy for gastric cancer (GC).

Methods: A post hoc analysis was performed in patients who participated in a phase 3 randomized clinical trial of ICG-guided laparoscopic radical gastrectomy vs. conventional laparoscopic radical gastrectomy from November 2018 to July 2019. The VFA was calculated based on preoperative computed tomography images. Short-term efficacy included the quality of lymph node (LN) dissection and surgical outcomes, while long-term efficacy included overall survival (OS) and recurrence-free survival (RFS).

Results: This study included 126 patients each in the ICG (high-VFA, n=43) and non-ICG groups (high-VFA, n=38). Compared with the non-ICG group, the ICG group had significantly more retrieved LNs (low-VFA: 50.1 vs. 43.9, P=0.001; high-VFA: 49.6 vs. 37.5, P<0.001) and a significantly lower LN noncompliance rate (low-VFA: 32.5% vs. 50.0%, P=0.020; high-VFA: 32.6% vs. 73.7%, P<0.001), regardless of the VFA. The ICG group had a shorter postoperative hospital stay and fewer intra-abdominal infections than the ICG group in the high-VFA patients (P=0.025 and P=0.020, respectively) but not in the low-VFA patients. Regardless of the VFA, the 3-year OS (RFS) was better in the ICG group than in the non-ICG group [low-VFA: 83.1% (76.9%) vs. 73.9% (67.0%); high-VFA: 90.7% (90.7%) vs. 73.7% (73.5%); P for interaction =0.474 (0.547)].

Conclusions: The short- and long-term efficacies of ICG tracing were not influenced by visceral obesity.

Objective: Hepatocellular carcinoma (HCC) is a prevalent malignancy with poor survival. Different cell types in the tumor microenvironment participate in the tumorigenesis and progression of HCC. This study aimed to analyze the immune microenvironment of HCC and its relationship with clinical outcomes.

Methods: We analyzed HCC RNA-seq for cell type identification and prognosis by estimating relative subsets of RNA transcripts using CIBERSORTx. The interaction between B cells and macrophages in HCC was analyzed using a Hepa1-6 orthotopic transplantation mouse model and flow cytometry. The effect of Zinc finger protein 296 (ZNF296) on the interaction of B cells and macrophages was verified using human HCC tissues analyzed through western blot, quantitative real-time polymerase chain reaction (qPCR), and multiplex immunofluorescence. A comparative analysis of immune cells associated with HCC prognosis was performed using RNA-seq data from The Cancer Genome Atlas (TCGA), bulk multimodal data, and single-cell transcriptomic data from existing HCC single-cell transcriptomic data employing the Single Cell Inferred Site Specific Omics Resource for Tumor Microenvironments (SCISSOR).

Results: Liver hepatocellular carcinoma (LIHC) RNA-seq analysis of TCGA showed that high eosinophil infiltration promoted HCC progression. The proportion of B cells correlated with that of macrophages (r=-0.24) and affected the infiltration and programmed death ligand 1 (PD-L1) expression of macrophages in HCC. ZNF296 may participate in the interaction between B cells and macrophages to accelerate the HCC progression by regulating PAFAH1B3 and H2AFX. Moreover, ZNF296 expression positively correlated with LAG3 (r=0.27) and CTLA4 (r=0.31) expression levels. Among the immune cell phenotypes related to survival and death identified by SCISSOR analysis, T cells correlated with an excellent prognosis of HCC. The normal function of liver and dendritic cells was also associated with a good prognosis in HCC.

Conclusions: This study analyzed the interaction of the immune microenvironment with HCC prognosis, identifying ZNF296 as a promising diagnostic and therapeutic target for HCC.

Objective: We aimed to compare the quality-adjusted time without symptoms or toxicity (Q-TWiST) in acute myeloid leukemia (AML) patients who received haploidentical-related donor (HID) and identical sibling donor (ISD) hematopoietic stem cell transplantation (HSCT).

Methods: Five clinical health states were defined: toxicity (TOX), acute graft-versus-host disease (GVHD), chronic GVHD (cGVHD), time without symptoms and toxicity (TWiST) and relapse (REL). The equation used in this study was as follows: Q-TWiST=U_TOX × TOX + U_TWiST × TWiST + U_REL × REL + U_aGVHD × aGVHD + U_cGVHD × cGVHD.

Results: A total of 239 AML patients were enrolled. We established a mathematical model, i.e., Q-TWiST HID HSCT > Q-TWiST ISD HSCT, to explore the range of utility coefficients satisfying the inequality. Based on the raw data, the utility coefficient is equivalent to the following inequality: [Formula: see text][Formula: see text]. The model showed that when [Formula: see text], [Formula: see text], and [Formula: see text] were within the range of 0-1, as well as when [Formula: see text] was within the range of 0-0.569, the inequality Q-TWiST HID HSCT > Q-TWiST ISD HSCT was valid. According to the results of the ChiCTR1800016972 study, the median coefficients of TOX, acute GVHD (aGVHD), and cGVHD were 0.56 (0.41-0.76), 0.56 (0.47-0.72), and 0.54 (0.37-0.79), respectively. We selected a series of specific examples of the coefficients, i.e., [Formula: see text]=0.5, [Formula: see text]=0.05, [Formula: see text]=0.5, and [Formula: see text]=0.5. The Q-TWiST values of ISD and HID HSCT were 896 and 900 d, respectively (P=0.470).

Conclusions: We first observed that Q-TWiST was comparable between AML patients receiving HID HSCT and those receiving ISD HSCT.

Objective: Several studies have been conducted on the effects and toxicity of adding oxaliplatin to fluorouracil-based or capecitabine-based chemoradiotherapy (CRT) regimens as significantly increasing the toxic response without benefit to survival. In this study, we further explored the role of these two postoperative CRT regimens in patients with pathological stage N2 rectal cancer.

Methods: This study was a subgroup analysis of a randomized clinical trial. A total of 180 patients with pathological stage N2 rectal cancer were eligible, 85 received capecitabine with radiotherapy (RT), and 95 received capecitabine and oxaliplatin with RT. Patients in both groups received adjuvant chemotherapy [capecitabine and oxaliplatin (XELOX); or fluorouracil, leucovorin, and oxaliplatin (FOLFOX)] after CRT.

Results: At a median follow-up of 59.2 [interquartile range (IQR), 34.0-96.8] months, the three-year disease- free survival (DFS) was 53.3% and 64.9% in the control group and the experimental group, respectively [hazard ratio (HR), 0.63; 95% confidence interval (95% CI), 0.41-0.98; P=0.04]. There was no significant difference between the groups in overall survival (OS) (HR, 0.62; 95% CI, 0.37-1.05; P=0.07), the incidence of locoregional recurrence (HR, 0.62; 95% CI, 0.24-1.64; P=0.33), the incidence of distant metastasis (HR, 0.67; 95% CI, 0.42-1.06; P=0.09) and grade 3-4 acute toxicities (P=0.78). For patients with survival longer than 3 years, the conditional overall survival (COS) was significantly better in the experimental group (HR, 0.39; 95% CI, 0.16-0.96; P=0.03).

Conclusions: Our results indicated that adding oxaliplatin to capecitabine-based postoperative CRT is safe and effective in patients with pathological stage N2 rectal cancer.

Objective: Genome-wide association studies (GWAS) have identified over 150 risk loci linked to colorectal cancer (CRC), including the 17p13.3 locus with the tag single nucleotide polymorphism (SNP) rs12603526 in the Asian population. However, the specific causal gene and the functional regulatory mechanisms in this region remain unresolved, necessitating further investigation to elucidate the underlying mechanisms of CRC.

Methods: We employed an RNA interference-based functional approach to identify genes critical for CRC cell proliferation at the GWAS locus 17p13.3. Bioinformatic fine-mapping analysis was conducted to prioritize causal variants. A large-scale study involving 7,013 cases and 7,329 controls from a Chinese population, along with another cohort of 5,158 cases and 20,632 controls from the UK Biobank, was performed to validate the association between the candidate variant and the gene. A series of biological experiments was conducted to explore the function of the candidate gene and its regulatory mechanisms.

Results: We identified FAM57A as a key oncogene that promotes CRC cell proliferation, and confirmed its carcinogenic role through in vitro proliferation assays. The variant rs526835 was prioritized as a causal candidate for CRC risk, located in a functional region with enhancer properties, and showed a significant quantitative association with FAM57A expression. The rs526835 [T] variant was associated with a 1.17-fold increase in CRC risk [95% confidence interval (95% CI): 1.11-1.23, P=1.23×10^-9] in the large-scale Chinese cohort, which was further corroborated in the UK Biobank cohort. Mechanistically, we demonstrated that rs526835 enhances a promoter-enhancer interaction mediated by the transcription factor JUN, leading to increased expression of FAM57A.

Conclusions: We reveal the underlying mechanisms of CRC predisposition at the GWAS locus 17p13.3. Additionally, our findings highlight the critical role of FAM57A in CRC pathogenesis and introduce a novel enhancer-promoter interaction between FAM57A and rs526835, which could inform future precision prevention and personalized cancer therapies.

Biliary tract cancer (BTC) is a group of rare malignancies that affect the gallbladder and bile ducts. Although rare, BTC is becoming a significant public health burden in China, particularly among males and older individuals. The increasing trends in BTC incidence and mortality in China are influenced by various demographic, environmental, and lifestyle factors. In this review, we examine available epidemiological data on the incidence, mortality, prognosis, and trends of different BTC subtypes in China. We also discuss the challenges and opportunities for improving the prevention, diagnosis, and management of BTC in China, and identify areas for further research and intervention. The article aims to provide a better understanding of the epidemiological features of BTC in China and to inform public health strategies and clinical practice.

Objective: The assessment of lateral lymph node metastasis (LLNM) in patients with papillary thyroid carcinoma (PTC) holds great significance. This study aims to develop and evaluate a deep learning-based automatic pipeline system (DLAPS) for diagnosing LLNM in PTC using computed tomography (CT).

Methods: A total of 1,266 lateral lymph nodes (LLNs) from 519 PTC patients who underwent CT examinations from January 2019 to November 2022 were included and divided into training and validation set, internal test set, pooled external test set, and prospective test set. The DLAPS consists of an auto-segmentation network based on RefineNet model and a classification network based on ensemble model (ResNet, Xception, and DenseNet). The performance of the DLAPS was compared with that of manually segmented DL models, the clinical model, and Node Reporting and Data System (Node-RADS). The improvement of radiologists' diagnostic performance under the DLAPS-assisted strategy was explored. In addition, bulk RNA-sequencing was conducted based on 12 LLNs to reveal the underlying biological basis of the DLAPS.

Results: The DLAPS yielded good performance with area under the receiver operating characteristic curve (AUC) of 0.872, 0.910, and 0.822 in the internal, pooled external, and prospective test sets, respectively. The DLAPS significantly outperformed clinical models (AUC 0.731, P<0.001) and Node-RADS (AUC 0.602, P<0.001) in the internal test set. Moreover, the performance of the DLAPS was comparable to that of the manually segmented deep learning (DL) model with AUCs ranging 0.814-0.901 in three test sets. Furthermore, the DLAPS-assisted strategy improved the performance of radiologists and enhanced inter-observer consistency. In clinical situations, the rate of unnecessary LLN dissection decreased from 33.33% to 7.32%. Furthermore, the DLAPS was associated with the cell-cell conjunction in the microenvironment.

Conclusions: Using CT images from PTC patients, the DLAPS could effectively segment and classify LLNs non-invasively, and this system had a good generalization ability and clinical applicability.