Complement and coagulation cascades pathway correlates with chemosensitivity and overall survival in patients with soft tissue sarcoma

Zhang, Jing; Chen, Maoshan; Zhao, Yuanyuan; Xiong, Huihua; Sneh, Tal; Yang, Fan; Wang, Jianhua; Xiao, Zhijie; Chen, Gong

doi:10.1016/j.ejphar.2020.173121

Cited by 39 publications

(28 citation statements)

References 29 publications

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“…C3AR1 is a hub mRNA for multiple myeloma (22), colon cancer (23) and melanoma (24). C3AR1 may predict chemotherapy resistance and outcomes of soft tissue sarcomas (25). Metastatic osteosarcoma leads to poor clinical outcomes, especially lung metastases.…”

Section: Discussionmentioning

confidence: 99%

C3AR1 mRNA as a Potential Therapeutic Target Associates With Clinical Outcomes and Tumor Microenvironment in Osteosarcoma

Zou

Liu²,

Wang³

et al. 2021

Front. Med.

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Objective: Targeting cancer-specific messenger RNAs (mRNAs) may offer novel insights into therapeutic strategies in osteosarcoma. This study aimed to discover possible osteosarcoma-specific mRNA and probe its biological functions.Methods: Based on mRNA-seq data from the TARGET database, stromal and immune scores were estimated for each osteosarcoma sample via the ESTIMATE algorithm. Stromal and immune mRNAs were obtained via integration of differentially expressed mRNAs between high and low stromal / immune score groups. Among hub and prognostic mRNAs, C3AR1 mRNA was focused and its prognostic value was assessed. The associations between C3AR1 mRNA and immune cells were analyzed via the CIBERSORT algorithm. Its expression was verified in osteosarcoma tissues and cells by RT-qPCR and western blot. The functions of C3AR1 were investigated by a series of experiments.Results: Low stromal and immune scores were both indicative of unfavorable outcomes for osteosarcoma patients. Eighty-eight up-regulated and seven down-regulated stromal and immune mRNAs were identified. Among 30 hub mRNAs, low expression of C3AR1 mRNA indicated worse outcomes than its high expression. There was a lower mRNA expression of C3AR1 in metastatic than non-metastatic osteosarcoma. C3AR1 mRNA was closely correlated to various immune cells such as macrophages. C3AR1 was verified to be down-regulated in osteosarcoma tissues and cells. Its overexpression suppressed proliferation, migration and invasion and induced apoptosis in osteosarcoma cells.Conclusion: C3AR1 mRNA could be a promising therapeutic target for osteosarcoma, linked with prognosis and tumor microenvironment.

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Section: Discussionmentioning

confidence: 99%

C3AR1 mRNA as a Potential Therapeutic Target Associates With Clinical Outcomes and Tumor Microenvironment in Osteosarcoma

Zou

Liu²,

Wang³

et al. 2021

Front. Med.

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“…C1QC belongs to C1Q and plays an important role in adaptive and innate immune responses. Studies have shown that C1QC can promote the adhesion, migration and proliferation of malignant pleural mesothelioma [25], as well as the increase in C1QC levels in patients with sarcoma, and C1Q1 is associated with poor prognosis [26]. High expression of the COL1A1 gene will cause unrestricted growth factors which, in turn, will benefit tumor proliferation [27].…”

Section: Discussionmentioning

confidence: 99%

Identification of a Prognostic Signature Model with Tumor Microenvironment for predicting Disease-free Survival after Radical Prostatectomy

Zhao¹,

Zhang²,

Shi³

et al. 2021

J. Cancer

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Background: The tumor microenvironment (TME) and immune checkpoint inhibitors have been shown to promote active immune responses through different mechanisms. We attempted to identify the important prognostic genes and prognostic characteristics related to TME in prostate cancer (PCa). Methods: The gene transcriptome profiles and clinical information of PCa patients were obtained from The Cancer Genome Atlas (TCGA) database, and the immune and stromal scores were calculated by the ESTIMATE algorithm. We evaluated the prognostic value of the risk score (RS) model based on univariate Cox analysis and least absolute shrinkage and selection operation (LASSO) Cox regression analysis and established a nomogram to predict disease-free survival (DFS) in PCa patients. The GSE70768 dataset was utilized for external validation. Twenty-two subsets of tumor-infiltrating immune cells were analyzed using the CIBERSORT algorithm. Results: In this study, the patients with higher immune/stromal scores were associated with a worse DFS, higher Gleason score, and higher pathological T stage. Based on the immune and stromal scores, 515 differentially expressed genes (DEGs) were identified. The univariate Cox and LASSO Cox regression models were employed to select 18 DEGs from 515 DEGs and construct an RS model. The DFS of the high-RS group was significantly lower than that of the low-RS group (P<0.001). The AUCs for the 1-year, 3-year and 5-year DFS rates in the RS model were 0.890, 0.877 and 0.841, respectively. A nomogram of DFS was established based on the RS and Gleason score, and the AUCs for the 1-year, 3-year and 5-year DFS rates in the nomogram were 0.907, 0.893, and 0.872, respectively. These results were further validated in the GSE70768 dataset. In addition, the proportion of Tregs was determined to be higher in high-RS patients (P<0.05), and the expression levels of five immune checkpoints (CTLA-4, PD-1, LAG-3, TIM-3 and TIGIT) were observed to be higher in high-RS patients (P<0.05). Conclusions: Our study established and validated an 18-gene prognostic signature model associated with TME, which might serve as a prognosis stratification tool to predict DFS in PCa patients after radical prostatectomy.

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“…The complement and coagulation cascades, which function as major proteolytic cascades in blood serum, are reported to be composed of more than 35 soluble plasma proteins, and recent evidence suggests that the complement and coagulation cascades mediate the response to acute injury by limiting bleeding and pathogen invasion and facilitating wound healing [33,[40][41][42]. Additionally, several studies have shown that the complement and coagulation cascades are not merely processes reactive to in ammation, immunity and haemostasis but rather critical determinants of liver disease pathogenesis [34,37].…”

Section: Discussionmentioning

confidence: 99%

Serum Proteomic Profiling in Patients with Advanced Schistosoma Japonicum-Induced Hepatic Fibrosis

Huang

Yin

Zhang

et al. 2021

Preprint

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Background: Schistosoma japonicum (S. japonicum) is a parasitic flatworm that is the aetiological agent of human schistosomiasis, an important cause of hepatic fibrosis. Schistosomiasis-induced hepatic fibrosis is a consequence of the highly fibrogenic nature of egg-induced granulomatuous lesions, the main pathogenic factor of schistosomiasis. Although global awareness of the association between schistosomiasis-indued hepatic fibrosis and s. japonicum infection is increasing, little is known about the mechanism mediating the rapid progression to schistosomiasis in cirrhotic patients.Methods: We systematically used data-independent acquisition (DIA)-based liquid chromatography-mass spectrometry to identify differentially expressed proteins in serum samples from patients with advanced S. japonicum-induced hepatic fibrosis.Results: On the basis of our analysis, we identified 1,144 proteins, among which 67 were differentially expressed between the healthy control and SHF-F2 groups and 214 were differentially expressed between the SHF-F2 and SHF-F4 groups (up- or downregulation of at least 1.5-fold in serum samples). Furthermore, our results indicated that two selected proteins (C1QA and CFD) are potential biomarkers for distinguishing patients with cirrhosis resulting from S. japonicum infection.Conclusions: This report is the first to provide a global proteomic profile of serum samples from patients with advanced S. japonicum-induced hepatic fibrosis. Our results shed new light on the molecular mechanisms that are dysregulated in and contribute to the pathogenesis of schistosomiasis-induced hepatic fibrosis. C1QA and CFD are promising diagnostic markers for patients with cirrhosis resulting from S. japonicum infection, although further large-scale studies are needed. Our DIA-based quantitative proteomic analysis revealed molecular differences among individuals with different stages of advanced S. japonicum-induced hepatic fibrosis and might provide fundamental information for further detailed investigations.

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Complement and coagulation cascades pathway correlates with chemosensitivity and overall survival in patients with soft tissue sarcoma

Cited by 39 publications

References 29 publications

C3AR1 mRNA as a Potential Therapeutic Target Associates With Clinical Outcomes and Tumor Microenvironment in Osteosarcoma

C3AR1 mRNA as a Potential Therapeutic Target Associates With Clinical Outcomes and Tumor Microenvironment in Osteosarcoma

Identification of a Prognostic Signature Model with Tumor Microenvironment for predicting Disease-free Survival after Radical Prostatectomy

Serum Proteomic Profiling in Patients with Advanced Schistosoma Japonicum-Induced Hepatic Fibrosis

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