Analysis on the Expression of Basement Membrane Protein in Endometrial Carcinoma and Its Relationship with Immune Invasion
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摘要:
目的 探讨Hub基因与子宫内膜癌的预后、免疫浸润及泛癌的关系，建立临床预后模型。 方法 利用癌症基因图谱（the cancer genome atlas，TCGA）子宫内膜癌数据库中的子宫内膜癌组织及癌旁组织表达谱和临床信息，筛选出差异表达基因，对LncRNA共表达的mRNA进行GO富集分析及KEGG信号通路分析，将子宫内膜癌与癌旁组织的差异基因与基底膜蛋白基因进行交集，将筛选出的差异表达基因与生存状态、生存时间进行合并通过Lasso-cox回归分析筛选出Hub基因，利用多因素Cox回归分析建立预后模型，进一步进行泛癌分析以及免疫浸润相关性分析。 结果 确定了6个与子宫内膜癌患者预后相关的基底膜蛋白Hub基因，ADAMTS5、EVA1C、THBS4、CTSD、ITGAV和LAMA1，发现患者随着风险评分增加，患者生存率明显下降。进行泛癌分析发现这6个基因在大多数癌症类型中显著差异（P < 0.05），且在多形性胶质母细胞瘤（glioblastoma multiform，GBMLGG）、脑低级别胶质瘤（low grade glioma，LGG）、急性髓细胞样白血病（acute myeloid leukemia，LAML）、葡萄膜黑色素瘤（uveal melanom，UVM）、肾上腺皮质癌（adrenocortical carcinom，ACC）等癌症中高表达预后差。并探究了这些基因在肿瘤免疫治疗中的潜在作用发现与Th17 cells、Th2 cells 、NK CD56bright cells等免疫细胞存在显著负相关，与Tcm、iDC、Eosinophils、aDC等免疫细胞存在显著正相关。 结论 基底膜蛋白基因在子宫内膜癌的诊断和预后方面有较高的临床价值，可作为子宫内膜癌患者的预后标志物和潜在治疗靶点。 Abstract:Objective Immune infiltration, as well as their implications across various cancers, and to establish a clinical prognostic model based on the findings. Methods The expression profile and clinical information of endometrial cancer tissue and adjacent tissues in TCGA endometrial cancer database were used, the differential expression genes were screened out for analysis, and the mRNA co-expressed by LncRNA was analyzed by GO enrichment and KEGG signaling pathway.The differential genes between endometrial cancer and adjacent tissues were intersected with the basement membrane protein genes. The selected differentially expressed genes were combined with survival status and survival time to screen out Hub genes by Lasso-cox regression analysis. Multivariate Cox regression analysis was used to establish a prognostic model, and pan-cancer analysis and immunoinfiltration correlation analysis were further performed. Results Six basal membrane protein Hub genes, ADAMTS5, EVA1C, THBS4, CTSD, ITGAV and LAMA1, were identified as associated with the prognosis of patients with endometrial cancer, and found that the survival rate of patients decreased significantly with the increase of risk score. Pan-cancer analysis found that these 6 genes were significantly different in most cancer types, and high expression in GBMLGG （glioma）, LGG （low-grade glioma of the brain）, LAML （acute myeloid leukemia）, UVM （Uveal melanoma）, ACC （adrenal cortical cancer） and other cancers had poor prognosis. The potential role of these genes in tumor immunotherapy was also explored, and significant negative correlation was found with Th17 cells, Th2 cells, NK CD56 bright cells and other immune cells, and significant positive correlation was found with Tcm, iDC, Eosinophils, aDC and other immune cells. Conclusion Basal membrane protein gene has high clinical value in the diagnosis and prognosis of endometrial cancer, and can be used as a prognostic marker and potential therapeutic target for patients with endometrial cancer. -
Key words:
- Basement membrane protein gene /
- Endometrial carcinoma /
- Prognosis /
- Immune infiltration
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图 1 子宫内膜癌组织与癌旁组织筛选差异基因
A:火山图；B:DEG热图；C:GO富集分析；D:KEGG富集分析
Figure 1. Screening of differential genes between endometrial carcinoma and adjacent tissues
图 2 基因交集与建立预后模型
A：子宫内膜癌与基底膜基因交集的韦恩图筛查108个基因；B、C： Lasso-cox回归筛选出11个基因；D：多因素cox回归筛选出6个基因
Figure 2. Gene intersection and establishment of prognosis model
图 3 风险评分模型的预后
A：11个显著基因表达热图；B：6个基因ROC曲线；C：6个基因Kaplan-Meier生存曲线
Figure 3. Prognosis of risk scoring model
图 4 泛癌分析
A-F：比较TCGA数据库和GTEx数据库中ADAMTS5、EVA1C、THBS4、CTSD、ITGAV、LAMA1基因表达差异的匹配分析。*P < 0.05；**P < 0.01；P < 0.001；***P < 0.0001。
Figure 4. Pan-cancer analysis
图 5 泛癌分析
A：ADAMTS5在泛癌中的预后表达；B：BEVA1C在泛癌中的预后表达；C：THBS4在泛癌中的预后表达（GBMLGG:胶质瘤; LGG:脑低级别胶质瘤;SARC:肉瘤; COADREAD：结直肠癌）。
Figure 5. Pan-cancer analysis
图 6 泛癌分析
A：CTSD在泛癌中的预后表达；B：ITGAV在泛癌中的预后表达；C：LAMA1在泛癌中的预后表达（GBMLGG:胶质瘤; LGG:脑低级别胶质瘤; KIPAN:混合肾癌; LGG:脑低级别胶质瘤; SARC:肉瘤; KIRC:肾透明细胞癌; UVMU:葡萄膜黑色素瘤; ACC:肾上腺皮质癌）。
Figure 6. Pan-cancer analysis
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[1] Wang N,Zhang J,Fan X,et al. Identification of risk factors for the prognosis of Chinese patients with endometrial carcinoma[J]. Medicine (Baltimore),2021,100(38):e27305. [2] Li Y T,Yang S T,Wang P H. Molecular pathology and prognosis of endometrial cancer[J]. Taiwan J Obstet Gynecol,2022,61(6):921-922. doi: 10.1016/j.tjog.2022.06.011 [3] Maheshwari E,Nougaret S,Stein E B,et al. Update on MRI in evaluation and treatment of endometrial cancer[J]. Radiographics,2022,42(7):2112-2130. [4] Liu Y,Li H,Zhao C,et al. MicroRNA-101 inhibits angiogenesis via COX-2 in endometrial carcinoma[J]. Mol Cell Biochem,2018,448(2):61-69. doi: 10.1007/s11010-018-3313-0 [5] Nees L K,Heublein S,Steinmacher S,et al. Endometrial hyperplasia as a risk factor of endometrial cancer[J]. Arch Gynecol Obstet,2022,306(2):407-421. [6] Crosbie E J,Kitson S J,Mcalpine J N,et al. Endometrial cancer[J]. Lancet,2022,399(10333):1412-1428. doi: 10.1016/S0140-6736(22)00323-3 [7] Raglan O,Kalliala I,Markozannes G,et al. Risk factors for endometrial cancer: An umbrella review of the literature[J]. Int J Cancer,2019,145(7):1719-1730. doi: 10.1002/ijc.31961 [8] Marin-jimenez J A,Garcia-mulero S,Matias-guiu X,et al. Facts and hopes in immunotherapy of endometrial cancer[J]. Clin Cancer Res,2022,28(22):4849-4860. doi: 10.1158/1078-0432.CCR-21-1564 [9] Karpel H,Slomovitz B,Coleman R L,et al. Biomarker-driven therapy in endometrial cancer[J]. Int J Gynecol Cancer,2023,33(3):343-350. doi: 10.1136/ijgc-2022-003676 [10] Wilson S E. Defective perlecan-associated basement membrane regeneration and altered modulation of transforming growth factor beta in corneal fibrosis[J]. Cell Mol Life Sci,2022,79(3):144-159. [11] Wilson S E. Fibrosis Is a Basement membrane-related disease in the cornea: Injury and defective regeneration of basement membranes may underlie fibrosis in other organs[J]. Cells,2022,11(2):309-330. doi: 10.3390/cells11020309 [12] Kuang H,Liu J,Jia X Y,et al. Autoimmunity in anti-glomerular basement Membrane Disease: A Review of Mechanisms and Prospects for Immunotherapy[J]. Am J Kidney Dis,2023,81(1):90-99. doi: 10.1053/j.ajkd.2022.07.006 [13] Mukwaya A,Jensen L,Lagali N. Relapse of pathological angiogenesis: Functional role of the basement membrane and potential treatment strategies[J]. Exp Mol Med,2021,53(2):189-201. [14] Kanazawa Y,Nagano M,Koinuma S,et al. Effects of aging on basement membrane of tibialis anterior muscle during recovery following muscle injury in rats[J]. Microscopy (Oxf),2022,71(4):245-248. doi: 10.1093/jmicro/dfac016 [15] Fitzgerald J. WARP: A unique extracellular matrix component of cartilage,muscle,and endothelial cell basement membranes[J]. Anat Rec (Hoboken),2020,303(6):1619-1623. [16] Nissen N I,Karsdal M,Willumsen N. Collagens and cancer associated fibroblasts in the reactive stroma and its relation to Cancer biology[J]. J Exp Clin Cancer Res,2019,38(1):115-127. doi: 10.1186/s13046-019-1110-6 [17] Banerjee S,Lo W C,Majumder P,et al. Multiple roles for basement membrane proteins in cancer progression and EMT[J]. Eur J Cell Biol,2022,101(2):151220. doi: 10.1016/j.ejcb.2022.151220 [18] Siegel R L,Miller K D,Fuchs H E,et al. Cancer statistics,2022[J]. CA Cancer J Clin,2022,72(1):7-33. doi: 10.3322/caac.21708 [19] Liu S J,Dang H X,Lim D A,et al. Long noncoding RNAs in cancer metastasis[J]. Nat Rev Cancer,2021,21(7):446-460. [20] Li X,Kuang Q,Peng M,et al. Basement membrane-associated lncRNA risk model predicts Prognosis and Guides Clinical Treatment in Clear Cell Renal Cell Carcinoma[J]. Biomedicines,2023,11(10):2635-2655. doi: 10.3390/biomedicines11102635 [21] 安梦霞,王萍玉. 基于铜死亡相关LncRNAs构建肺鳞癌预后预测模型[J]. 肿瘤防治研究,2023,50(11):1084-1090. [22] Jayadev R,Morais M,Ellingford J M,et al. A basement membrane discovery pipeline uncovers network complexity,regulators,and human disease associations[J]. Sci Adv,2022,8(20):eabn2265. doi: 10.1126/sciadv.abn2265 [23] Siegel L,Miller K D,Wagle N S,et al. Cancer statistics,2023[J]. CA Cancer J Clin,2023,73(1):17-48. doi: 10.3322/caac.21763 [24] Li X,Fliegel L. Permissive role of Na(+)/H(+) exchanger isoform 1 in migration and invasion of triple-negative basal-like breast cancer cells[J]. Mol Cell Biochem,2022,477(4):1207-1216. [25] Deutsch J S,Lai J,Schenk K M,et al. Immune microenvironment of basal cell carcinoma and tumor regression following combined PD-1/LAG-3 blockade[J]. J Immunother Cancer,2023,11(12):e007463. doi: 10.1136/jitc-2023-007463 -
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