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Prognostic and immunological roles of heat shock protein A4 in lung adenocarcinoma

World Journal of Clinical Oncology 2024年第1期15卷 45-61页

作者： Xuan Wu Shen-Ying Yang Yi-Hua Zhang Jin-Zhou Fang Shuai Wang Zhi-Wei Xu Xiao-Ju Zhang Department of Respiratory and Critical Care Medicine Zhengzhou University People’s HospitalZhengzhou 450008Henan ProvinceChina Graduate School Xinxiang Medical UniversityXinxiang 453003Henan ProvinceChina Department of Pulmonary and Critical Care Medicine Zhengzhou University People’s HospitalZhengzhou 450008Henan ProvinceChina

BACKGROUND Heat shock protein A4(HSPA4)belongs to molecular chaperone protein family which plays important roles within variable cellular activities,including cancer initiation and progression.However,the prognostic and immunological significance of HSPA4 in lung adenocarcinoma(LUAD)has not been revealed yet.AIM To explore the prognostic and immunological roles of HSPA4 to identify a novel prognostic biomarker and therapeutic target for LUAD.METHODS We assessed the prognostic and immunological significance of HSPA4 in LUAD using data from The Cancer Genome Atlas database.The association between HSPA4 expression and clinical-pathological features was assessed through Kruskal-Wallis and Wilcoxon signed-rank test.Univariate/multivariate Cox regression analyses and Kaplan-Meier curves were employed to evaluate prognostic factors,including HSPA4,in LUAD.Gene set enrichment analysis(GSEA)was conducted to identify the key signaling pathways associated with HSPA4.The correlation between HSPA4 expression and cancer immune infiltration was evaluated using single-sample gene set enrichment analysis(ssGSEA).RESULTS Overexpressing HSPA4 was significantly related to advanced pathologic TNM stage,advanced pathologic stage,progression disease status of primary therapy outcome and female subgroups with LUAD.In addition,increased HSPA4 expression was found to be related to worse disease-specific survival and overall survival.GSEA analysis indicated a significant correlation between HSPA4 and cell cycle regulation and immune response,particularly through diminishing the function of cytotoxicity cells and CD8 T cells.The ssGSEA algorithm showed a positive correlation between HSPA4 expression and infiltrating levels of Th2 cells,while a negative correlation was observed with cytotoxic cell infiltration levels.CONCLUSION Our findings indicate HSPA4 is related to prognosis and immune cell infiltrates and may act as a novel prognostic biomarker and therapeutic target for LUAD.

关键词： Heat shock protein A4 Lung adenocarcinoma tumor-infiltration Prognosis T helper cells

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Prognosis and immunological role of HLA-DMA in lung adenocarcinoma

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BIOCELL 2023年第6期47卷 1279-1292页

作者： QIN YU CHEN CHEN HAIYAN ZHANG JIN CHEN JUNKANG SHEN JUN YAN Department of Imaging The Second Affiliated Hospital of Soochow UniversitySuzhou215000China Department of Imaging Dongtai People’s HospitalDongtai224000China Institute of Imaging Medicine Soochow UniversitySuzhou215000China Department of Orthopedics Dongtai People’s HospitalDongtai224000China Department of Orthopedics The Second Affiliated Hospital of Soochow UniversitySuzhou215000China Department of Pathology The Third People’s Hospital of NantongNantong226001China

Background:HLA-DMA presents pathogen-derived antigens to CD4+and CD8+T cells,respectively,and plays a significant part in initiating the immune response.So far,the impact of HLA expression on the prognosis of BC cells is controversial,because few studies have shown that the expressions of some HLA genes are related to the improvement of the survival rate.Up till now,however,the relationship between HLA-DMA and LUAD has not yet been assessed.Methods:We analyzed the TCGA database and assessed the prognostic value of HLA-DMA in LUAD.We conducted the Kruskal–Wallis and Wilcoxon signed-rank test and utilized logistic regression to assess the role of clinical-pathologic characteristics and HLA-DMA expression.Kaplan–Meier method and the multivariate and univariate Cox regression were also used for evaluating the prognosis-related factors of LUAD.GSEA was used to identify HLA-DMA-related key pathways.The ssGSEA of the TCGA data was used to investigate the correlations between HLA-DMA and cancer immune cell infiltration.Results:Low HLA-DMA expression was related to poorer disease-specific survival(DSS)and overall survival(OS)of LUAD patients.GSEA revealed that HLA-DMA was tightly interrelated with an immune response by the reactome activation of anterior hox genes in hindbrain development during the early embryogenesis signaling pathway.The expression of HLA-DMA was positively associated with cytotoxic cell infiltration and negatively related to the Th2 cell infiltration according to the ssGSEA.Western blotting and the CCK-8 assay showed that KD-HLA-DMA could significantly increase the proliferation of A549 cells and significantly reduce cell pyroptosis.Conclusion:All the observations implied that HLA-DMA was associated with patient prognosis and immune infiltration in LUAD.

关键词： HLA-DMA Lung adenocarcinoma tumor-infiltration Prognosis Cytotoxic cells

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MMP1 Is a Prognostic-Related Biomarker and Correlated with Immune infiltration in Breast Cancer

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Health 2022年第2期14卷 219-235页

作者： Xiangdong Wei Bin Zhang Baojun Pan Changle People’s Hospital Weifang China

Background: Matrix metalloproteinases 1 (MMP1) plays a role in cancer development and metastasis and high expression of MMP1 has been confirmed in various types of cancers. However, the correlation between MMP1 and prognosis and tumor-infiltration lymphocytes in breast cancer remains uncertain. In this present study, we analyzed MMP1 expression and correlation with prognosis of cancer patients in databases such as Oncomine, PrognoScan, and Kaplan-Meier plotter. In addition, we investigated the correlation of MMP1 with tumor-infiltrating immune cells in the different tumor microenvironments via tumor Immune Estimation Resource (TIMER). Methods: MMP1 expression was analyzed via the Oncomine database and tumor Immune Estimation Resource (TIMER) site. The prognosis of MMP1 on cancers was analyzed using Kaplan-Meier plotter, the PrognoScan database and Gene Expression Profiling Interactive Analysis (GEPIA). The correlations between MMP1 and cancer immune infiltration were investigated by TIMER. In addition, correlations betweenMMP1 expression and gene marker sets of immune infiltration were analyzed by TIMER and GEPIA. Results: MMP1 is highly expressed in most cancers and correlated to poor prognosis. MMP1 expression is significantly linked with a poorer prognosis in breast cancer (OS HR 1.78, 95% CI = 1.59 - 1.98, P −0.134, P = 2.17e-05), macrophage (R = 0.41, P = 1.11e-08), dendritic cell (R = 0.221, P = 2.92e-03) and NK cell (R = 0.213, P = 4.15e-03). Besides, MMP1 expression is significantly associated with the marker genes of immune cells (P Conclusions: Our study indicates that MMP1 is correlated with prognosis and immune infiltrating levels of CD8+ T cell, CD8+ T cell, macrophage, dendritic cell and NK cells in breast cancer. Besides, MMP1 expression potentially contributes to regulation of T cell, B cell, tumor-associated macrophages (TAMs), DCs, T cell exhaustion and Tregs in colon and gastric cancer. The results indicate that MMP1 can be used as a prognostic biomarker for determin

关键词： MMP1 Breast Cancer Prognosis tumor-infiltration

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