Tumor Immunophenotyping‐Derived Signature Identifies Prognosis and Neoadjuvant Immunotherapeutic Responsiveness in Gastric Cancer

Wang, Jia-Bin; Qiu, Qing-Zhu; Zheng, Qi; Zhao, Yajun; Xu, Yü; Zhang, Tao; Wang, Shuanhu; Wang, Quan; Jin, Qinwen; Ye, Yin-Hua; Li, Ping; Xie, Jian-Wei; Ji, Lin; Lü, Jun; Chen, Qi‐Yue; Cao, Long‐Long; Yang, Yinghong; Zheng, Chao‐Hui; Huang, Chang‐Ming

doi:10.1002/advs.202207417

Cited by 6 publications

(5 citation statements)

References 54 publications

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“…For example, a tumor immunophenotyping-derived signature constructed by Wang et al. can effectively evaluate the prognosis and response of GC patients to neoadjuvant ICI therapy ( 86 ). Additionally, Sui et al.…”

Section: Discussionmentioning

confidence: 99%

Identification and characterization of CLEC11A and its derived immune signature in gastric cancer

Zheng,

Gong,

et al. 2024

Front. Immunol.

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IntroductionC-type lectin domain family 11 member A (CLEC11A) was characterized as a growth factor that mainly regulates hematopoietic function and differentiation of bone cells. However, the involvement of CLEC11A in gastric cancer (GC) is not well understood.MethodsTranscriptomic data and clinical information pertaining to GC were obtained and analyzed from publicly available databases. The relationships between CLEC11A and prognoses, genetic alterations, tumor microenvironment (TME), and therapeutic responses in GC patients were analyzed by bioinformatics methods. A CLEC11A-derived immune signature was developed and validated, and its mutational landscapes, immunological characteristics as well as drug sensitivities were explored. A nomogram was established by combining CLEC11A-derived immune signature and clinical factors. The expression and carcinogenic effects of CLEC11A in GC were verified by qRT−PCR, cell migration, invasion, cell cycle analysis, and in vivo model analysis. Myeloid-derived suppressor cells (MDSCs), regulatory T cells (Tregs), M2 macrophages, and T cells in tumor samples extracted from mice were analyzed utilizing flow cytometry analysis.ResultsCLEC11A was over-expressed in GC, and the elevated CLEC11A expression indicated an unfavorable prognosis in GC patients. CLEC11A was involved in genomic alterations and associated with the TME in GC. Moreover, elevated CLEC11A was found to reduce the benefit of immunotherapy according to immunophenoscore (IPS) and the tumor immune dysfunction, exclusion (TIDE). After validation, the CLEC11A-derived immune signature demonstrated a consistent ability to predict the survival outcomes in GC patients. A nomogram that quantifies survival probability was constructed to improve the accuracy of prognosis prediction in GC patients. Using shRNA to suppress the expression of CLEC11A led to significant inhibitions of cell cycle progression, migration, and invasion, as well as a marked reduction of in vivo tumor growth. Moreover, the flow cytometry assay showed that the knock-down of CLEC11A increased the infiltration of cytotoxic CD8+ T cells and helper CD4+ T into tumors while decreasing the percentage of M2 macrophages, MDSCs, and Tregs.ConclusionCollectively, our findings revealed that CLEC11A could be a prognostic and immunological biomarker in GC, and CLEC11A-derived immune signature might serve as a new option for clinicians to predict outcomes and formulate personalized treatment plans for GC patients.

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Section: Discussionmentioning

confidence: 99%

Identification and characterization of CLEC11A and its derived immune signature in gastric cancer

Zheng,

Gong,

et al. 2024

Front. Immunol.

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“…The relationship between the prognosis of 10,050 patients with stomach cancer and various stages was analyzed by Kim et al [ 15 ]. According to the AJCC staging system of the 7th edition [ 28 ], stage III patients accounted for 25% of the patients. The 5-year OS rates of patients with stage Ia, Ib, IIa, IIb, IIIa, IIIb, IIIc and IV disease were 96.1%, 93.5%, 84.9%, 76.1%, 66.7%, 43.8%, 24.9% and 10.1%, respectively.…”

Section: Discussionmentioning

confidence: 99%

Analysis of multiple factors influencing the survival of patients with advanced gastric cancer

Zhu,

Ge,

Wen

et al. 2024

Aging

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Objective: The aim of this study was to investigate the main factors influencing the survival of patients with advanced gastric cancer. Methods: The clinicopathological data of 120 patients with advanced gastric cancer were analyzed retrospectively, and clinical and pathological data were collected. Tumor tissue staging and grading were reevaluated, and 5-year overall survival was followed up. The classified data were described by percentages, and the continuous data were described by standard deviations or medians. Univariate analysis was performed using the χ 2 test or rank-sum test, followed by Kaplan-Meier survival analysis to calculate the median survival time and 5-year cumulative survival. A multivariate Cox regression model was used to evaluate the independent risk factors affecting survival. The test level was α = 0.05. Results: Patients were followed up for 0 to 60 months, the 5-year overall survival rate was 36.2%, and the median survival time was 53.0 ± 1.461 months. K-M and log-rank test results revealed that tumor location, degree of differentiation, depth of invasion, regional lymph node involvement, and postoperative tumor stage were correlated with a decreased 5-year survival rate (P < 0.05). A multivariate Cox risk regression model was used to analyze the degree of histological differentiation (HR = 1.441; 95% CI = 1.049-1.979; P = 0.024), regional lymph node (HR = 1.626; 95% CI = 1.160-2.279; P = 0.005), and pTNM stage (HR = 2.266; 95% CI = 1.335-3.847; P = 0.002), which are independent risk factors for poor survival. Tumor location (P = 0.191), invasion depth (P = 0.579) and tumor size (P = 0.324) were not found to be independent risk factors. Conclusion: The degree of tumor differentiation, regional lymph node metastasis and postoperative pathological stage were found to be independent risk factors for 5-year overall survival in patients with advanced gastric cancer. Standardized and reasonable lymph node dissection and accurate postoperative pathological staging were very important.

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“…However, limited efficacy remains a challenge in most clinical settings and only a minority of patients benefit from this treatment, with even fewer achieving durable responses ( 36 ). The infiltrating immune cells in the TME are significantly associated with disease progression and therapeutic outcome of cancer patients ( 37 ). The TME contains a variety of cell types, including immune cells, stromal cells, and cancer cells as well as secreted factors which are often the targets for anti-tumor therapies ( 38 ).…”

Section: Discussionmentioning

confidence: 99%

Prognostic value and immune regulatory role of dynamin 1-like in lung adenocarcinoma

Song,

Wu,

Wang

et al. 2023

Transl Lung Cancer Res

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Background Lung adenocarcinoma (LUAD) is the most common histological subtype of non-small cell lung cancer (NSCLC), with poor treatment outcomes worldwide. Dynamin-related protein 1 (DRP1), which is encoded by the dynamin 1-like ( DNM1L ) gene, acts as a regulator of mitochondrial fission and plays crucial roles in tumor initiation and progression. However, the clinical value and immune regulation of DNM1L in LUAD have not been explored. Methods We comprehensively analyzed the expression of DNM1L in the LUAD cohort of the Human Protein Atlas (HPA) and the University of The ALabama at Birmingham CANcer data analysis Portal (UALCAN) databases. Kaplan-Meier plotter, in addition to the PrognoScan database, was used to estimate the correlation between DNM1L expression and survival outcome of LUAD patients. The association between the immune tumor microenvironment (TME) and DNM1L expression in LUAD was evaluated based on the Tumor IMmune Estimation Resource (TIMER)2.0 database. Finally, the functions of DNM1L were validated in vitro experiments, including reverse transcription-quantitative polymerase chain reaction (RT-qPCR), western blot, wound healing assays, and transwell assays. Results DNM1L was overexpressed in LUAD compared to healthy control tissues and was regarded as an independent prognostic factor. Overexpression of DNM1L was significantly related to clinical variables and poor survival outcomes of LUAD patients. Moreover, DNM1L expression was positively associated with the expression of key genes involved in the regulation of immune cell subsets, including T helper (Th)2 cells, Th cells, B cells, CD8 T cells, dendritic cells, and mast cells. In contrast, DNM1L was negatively correlated with the infiltrating levels of myeloid dendritic cells and B cells. Furthermore, DNM1L may play a role in regulating immune cell infiltration and have prognostic value in LUAD patients. Finally, the in vitro experiments showed that increased DNM1L significantly promoted the proliferation and migration of LUAD cells. Conclusions This study suggested that DNM1L may play an important role in regulating the proliferation and migration of LUAD cells as well as the infiltration of tumor-related immune cells, which suggests DNM1L was a potential therapeutic target in LUAD. Further studies are however warranted to define its exact mechanism of action and potential therapeutic significance in LUAD patients.

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Tumor Immunophenotyping‐Derived Signature Identifies Prognosis and Neoadjuvant Immunotherapeutic Responsiveness in Gastric Cancer

Cited by 6 publications

References 54 publications

Identification and characterization of CLEC11A and its derived immune signature in gastric cancer

Identification and characterization of CLEC11A and its derived immune signature in gastric cancer

Analysis of multiple factors influencing the survival of patients with advanced gastric cancer

Prognostic value and immune regulatory role of dynamin 1-like in lung adenocarcinoma

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