All Publications
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Efficacy and safety of dual blockade of HER2 and PD-1 in patients with HER2-positive gastric cancer: a retrospective, multicentre study.
Scientific reports
2024; 14 (1): 25030
Abstract
Human epidermal growth factor receptor 2 (HER2) expression is one of the most important pathological characteristics of gastric cancer. The positive rate of HER2 expression in patients with gastric cancer is approximately 20%. The phase III Keynote-811 study revealed that anti-HER2 and anti-PD-1 therapy combined with chemotherapy could significantly improve the objective response rate as first-line treatment in patients with HER2-positive advanced gastric cancer. In the present study, we aimed to evaluate the efficacy of combination therapy with trastuzumab and PD-1 inhibitors in patients with advanced HER2-positive gastric cancer in a real-world setting. Seventy-two HER2-positive gastric cancer patients from three hospitals in China were retrospectively reviewed. These patients were treated with trastuzumab plus one anti-PD-1 agent with or without chemotherapy. The overall response rate, progression-free survival and overall survival were assessed according to the Response Evaluation Criteria in Solid Tumours (RECIST 1.1). From January 2018 to October 2021, 72 patients with HER2-positive gastric cancer received trastuzumab and a PD-1 inhibitor with or without chemotherapy as neoadjuvant chemotherapy, first-line therapy, second-line therapy or salvage therapy. The ORR was 54.2% for all patients and 79.4% for previously untreated patients. The median PFS and median OS were 10 months (95% CI: 8-13 months) and 26.1 months (95% CI: 18.5-NA months), respectively, for all patients. Grade 3 adverse effects occurred in approximately 25% of patients. Immune-related adverse effects occurred in approximately 12.5% of patients. Trastuzumab and PD-1 inhibitor combination therapy with or without chemotherapy achieved satisfactory survival outcomes in patients with HER2-positive gastric cancer with acceptable safety.
View details for DOI 10.1038/s41598-024-76296-y
View details for PubMedID 39443515
View details for PubMedCentralID PMC11500361
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Immune microenvironment characteristics and their implications for immune checkpoint inhibitor efficacy in HER2-overexpressing gastric cancer
CLINICAL AND EXPERIMENTAL IMMUNOLOGY
2022; 207 (3): 318-328
Abstract
HER2-positive gastric cancer is a distinct tumor subtype, accounting for ~10% of gastric cancer cases. It is characterized by HER2 overexpression and responds well to HER2-targeting therapies. Recently, the addition of immune checkpoint inhibitors to HER2-targeting therapies produced satisfactory outcomes in these patients. In the present study, we used gene expression profiles and patient surgical sections to analyze the tumor immune microenvironment characteristics of gastric tumors with high HER2 expression. Several differentially enriched pathways were identified between the HER2 high-expression group and the low-expression group, such as pathways related to cytokine-cytokine receptor interactions, calcium signaling, and cell adhesion molecules. Tumors with high HER2 expression comprised fewer stromal cells and fewer immune cells, and had higher tumor purity. They also presented with lower expression of PD-1, PD-L1, CTLA-4, TIGIT, and LAG-3. In conclusion, our study provides a comprehensive blueprint of the immune microenvironment of HER2-positive gastric tumors. This analysis highlights the importance of considering the tumor microenvironment when assessing response to immune checkpoint inhibitors.
View details for DOI 10.1093/cei/uxac007
View details for Web of Science ID 000763017300001
View details for PubMedID 35553632
View details for PubMedCentralID PMC9113110
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Clinicopathologic features and treatment advances in cancers with HER2 alterations
BIOCHIMICA ET BIOPHYSICA ACTA-REVIEWS ON CANCER
2021; 1876 (2): 188605
Abstract
HER2 is one of the most important proteins of the epidermal growth factor receptor (EGFR) family, whose alterations include amplification, overexpression and gene mutation. Growing attention has been given to HER2 as a biomarker for prognosis, an indicator for treatment response and a target for new drugs. Tumors with HER2 alterations have been well studied in multiple locations as distinct entities for treatment, especially breast cancer, gastric cancer, lung cancer and colorectal cancer. These four cancers are the leading causes of cancer incidence and cancer-related death worldwide. The present study details the landscape of HER2 amplification/overexpression and mutations and gives an up-to-date analysis of current clinical trials in the four cancers mentioned above. Different HER2-altered cancers not only respond differently to HER2-targeting therapies but also display diverse survival outcomes. Even in the same type of cancer, HER2 amplification/overexpression differs from HER2 mutation in terms of clinicopathologic features and treatment strategies. As an emerging strategy in cancer treatment, immune checkpoint inhibitors demonstrate distinct outcomes in HER2-altered breast cancer, gastric cancer and lung cancer.
View details for DOI 10.1016/j.bbcan.2021.188605
View details for Web of Science ID 000697158300014
View details for PubMedID 34358635
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BRAF Mutation as a Potential Therapeutic Target for Checkpoint Inhibitors: A Comprehensive Analysis of Immune Microenvironment in BRAF Mutated Colon Cancer
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
2021; 9: 705060
Abstract
BRAF mutated colon cancer presents with poor survival, and the treatment strategies are controversial. The tumor microenvironment, which plays a key role in tumorigenesis as well as responses to treatments, of this subtype is largely unknown. In the present study, we analyzed the differences of immune microenvironments between BRAF mutated and BRAF wild-type colon cancer utilizing datasets from The Cancer Genome Atlas and Gene Expression Omnibus and confirmed the findings by tissue specimens of patients. We found that BRAF mutated colon cancer had more stromal cells, more immune cell infiltration, and lower tumor purity. Many immunotherapeutic targets, including PD-1, PD-L1, CTLA-4, LAG-3, and TIM-3, were highly expressed in BRAF mutated patients. BRAF mutation was also correlated with higher proportions of neutrophils and macrophages M1, and lower proportions of plasma cells, dendritic cells resting, and T cells CD4 naïve. In conclusion, our study demonstrates a different pattern of the immune microenvironment in BRAF mutated colon cancer and provides insights into the future use of checkpoint inhibitors in this subgroup of patients.
View details for DOI 10.3389/fcell.2021.705060
View details for Web of Science ID 000682897000001
View details for PubMedID 34381786
View details for PubMedCentralID PMC8350390
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The online-to-offline (O2O) food delivery industry and its recent development in China
EUROPEAN JOURNAL OF CLINICAL NUTRITION
2021; 75 (2): 232-237
Abstract
This paper offers a unique perspective about the development of the online-to-offline (O2O) food delivery industry from 2017 to 2019 in China. This study demonstrates the latest transformation and improvements of the O2O market that address some common problems in the early stages of the development of this raising industry in China. New strategies and regulations from the O2O platforms, food providers, and national and local governments are discussed. In our view, the mission of the O2O industry in general has shifted from pursuing enormous quantity to ensuring high quality. China's O2O food delivery industry warrants further attention and studies as it grows and develops into the future. We suggest future studies to work on its economic, behavioral, and health impacts on population level as it encompasses both great risks and rewards.
View details for DOI 10.1038/s41430-020-00842-w
View details for Web of Science ID 000613981900004
View details for PubMedID 33531631
View details for PubMedCentralID PMC7851805
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A double-edged sword: the association of daytime napping duration and metabolism related diseases in a Chinese population
EUROPEAN JOURNAL OF CLINICAL NUTRITION
2021; 75 (2): 291-298
Abstract
Some studies have suggested that daytime napping may increase the risk of type 2 diabetes. However, limited data have revealed the association between nap duration and other metabolic diseases. Data from the baseline survey of Lanxi Cohort Study, a population-based study of natural residents in Zhejiang Province, China, were used to investigate the relationship between nap duration and metabolic abnormalities.A total of 3236 participants underwent a physical examination, laboratory tests, and face to face interview. They were categorized into four groups according to nap duration. Logistic regression models were used to examine the odds ratios (ORs) of napping duration with four metabolism-related diseases. Stratified analysis was further used to explore the interaction effects of gender and age on results.Compared to the no daytime napping group, people who napped during the daytime for more than 1 h were independently associated with a greater prevalence of diabetes (OR 1.56). Those who napped during the daytime within a half hour showed a lower prevalence of fatty liver, dyslipidemia, and central obesity. To be more specific, those who habitually napped during the daytime for more than 1 h exhibited an increasing prevalence of diabetes among female older than 50 years old. Those who habitually napped during the daytime within a half hour exhibited a decreasing prevalence of fatty liver and dyslipidemia among male <50 years old, and that of central obesity among female <50 years old.Short daytime napping duration is associate with reduced rate of metabolism-related diseases and may protects people from negative health conditions, whereas long daytime napping duration is associate with higher prevalence of diabetes, which then can be harmful for health.
View details for DOI 10.1038/s41430-020-00777-2
View details for Web of Science ID 000582307100002
View details for PubMedID 33082534
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A microRNA disease signature associated with lymph node metastasis of lung adenocarcinoma
MATHEMATICAL BIOSCIENCES AND ENGINEERING
2020; 17 (3): 2557-2568
Abstract
Background: Lymph node metastasis (LNM) of lung cancer is an important factor associated with prognosis. Dysregulated microRNAs (miRNAs) are becoming a new powerful tool to characterize tumorigenesis and metastasis. We have developed and validated a miRNA disease signature to predict LNM in lung adenocarcinoma (LUAD). Method: LUAD miRNAs and clinical data from The Cancer Genome Atlas (TCGA) were obtained and divided randomly into training (n = 259) and validation (n = 83) cohorts. A miRNA signature was built using least absolute shrinkage and selection operator (LASSO) (λ =-1.268) and logistic regression model. The performance of the miRNA signature was evaluated using the area under curve (AUC) of receiver operating characteristic curve (ROC). We performed decision curve analysis (DCA) to assess the clinical usefulness of the signature. We also conducted a miRNA-regulatory network analysis to look for potential genes engaged in LNM in LUAD. Result: Thirteen miRNAs were selected to build our miRNA disease signature. The model showed good calibration in the training cohort, with an AUC of 0.782 (95% CI: 0.725-0.839). In the validation cohort, AUC was 0.691 (95% CI: 0.575-0.806). DCA demonstrated that the miRNA signature was clinically useful. Conclusion: The miRNA disease signature can be used as a noninvasive method to predict LNM in patients with lung adenocarcinoma objectively and the signature achieved high accuracy for prediction.
View details for DOI 10.3934/mbe.2020140
View details for Web of Science ID 000519873900040
View details for PubMedID 32233554
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Tumor clinicopathological characteristics and their prognostic value in mucinous colorectal carcinoma
FUTURE ONCOLOGY
2019; 15 (35): 4095-4104
Abstract
Aim: This study analyzed clinicopathological features of colorectal mucinous carcinoma and their prognostic values. Patients & method: This study enrolled 265 patients with mucinous colorectal cancer. Clinicopathological information and prognosis were reviewed retrospectively. Kaplan-Meier method, log- rank test and COX proportional hazard regression models were used. Results: In postoperative mucinous carcinoma patients (median age 56, 119 [44.9%] female), advanced tumor stage (odds ratio [OR]: 2.378; 95% CI: 1.512-3.741; p = 0.0002), poor differentiation (OR: 1.896; CI: 1.217-2.955; p = 0.0047) and right-sided tumors (OR: 2.421; CI: 1.145-5.102; p = 0.0206) were associated with shorter overall survival. Appendiceal/ileocecal cecal tumors were not different for prognosis. Conclusion: Mucinous colorectal carcinoma exhibits distinct tumor characteristics. Poor differentiation, advanced stage at presentation and the right side serve as negative prognostic factors.
View details for DOI 10.2217/fon-2019-0342
View details for Web of Science ID 000502552400009
View details for PubMedID 31773976
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Mucinous colorectal adenocarcinoma: clinical pathology and treatment options
CANCER COMMUNICATIONS
2019; 39: 13
Abstract
Mucinous colorectal adenocarcinoma is a distinct subtype of colorectal cancer (CRC) characterized by the presence of abundant extracellular mucin which accounts for at least 50% of the tumor volume. Mucinous colorectal adenocarcinoma is found in 10%-20% of CRC patients and occurs more commonly in female and younger patients. Moreover, mucinous colorectal adenocarcinoma is more frequently located in the proximal colon and diagnosed at an advanced stage. Based on its molecular context, mucinous colorectal adenocarcinoma is associated with the overexpression of mucin 2 (MUC2) and mucin 5AC (MUC5AC) proteins. At the same time, it shows higher mutation rates in the fundamental genes of the RAS/MAPK and PI3K/Akt/mTOR pathways. Mucinous colorectal adenocarcinoma also shows higher rates of microsatellite instability (MSI) than non-mucinous colorectal adenocarcinoma which might correlate it with Lynch syndrome and the CpG island methylator phenotype. The prognosis of mucinous colorectal adenocarcinoma as to non-mucinous colorectal adenocarcinoma is debatable. Further, the impaired responses of mucinous colorectal adenocarcinoma to palliative or adjuvant chemotherapy warrant more studies to be performed for a specialized treatment for these patients. In this review, we discuss the molecular background and histopathology of mucinous colorectal adenocarcinoma, and provide an update on its prognosis and therapeutics from recent literatures.
View details for DOI 10.1186/s40880-019-0361-0
View details for Web of Science ID 000463760100002
View details for PubMedID 30922401
View details for PubMedCentralID PMC6440160