|Table of Contents|

Construction and analysis of immune-related risk model for prognosis of bladder cancer

Journal Of Modern Oncology[ISSN:1672-4992/CN:61-1415/R]

Issue:
2021 05
Page:
811-818
Research Field:
Publishing date:

Info

Title:
Construction and analysis of immune-related risk model for prognosis of bladder cancer
Author(s):
SHI Hailin1; HE Tianji1; LIU Feng2; CAI Menghui2; GE Bo2
1.Department of Urology,Affiliated Hospital of Guilin Medical College，Guangxi Guilin 541001，China;2.Department of Urology,Second Affiliated Hospital of Guilin Medical College,Guangxi Guilin 541001，China.
Keywords:
bladder cancer; immune-related genes; risk model; TCGA; survival prognosis
PACS:
R737.14
DOI:
DOI:10.3969/j.issn.1672-4992.2021.05.020
Abstract:
Objective:To evaluate the prognosis of bladder cancer（BC） by constructing an immune-related risk model,and to explore the clinical application value of immune-related genes（IRGs） in BC.Methods:Respectively based on TCGA,ImmPort,Cistrom database,BC transcriptome sequencing data-seq,IRGs and Transcription factor (TFs) data were download.COX regression analysed differentially expressed IRGs.Risk score was calculated and Kaplan-Meier survival analysis was made.Differential expression of IRGs and TFs was analysed network regulation analysis.The differential expression of 22 immunoinfiltrating cells in BC was analyzed with Riskscore.Results:A total of 22 IRGs were significantly associated with the clinical outcome of BC patients.Functional enrichment analysis revealed that these genes were actively involved in acytokine-cytokine receptor interaction KEGG pathway.The immuno-risk model based on MMP9,PAEP,ADIPOQ,AHNAK,OAS1,RAC3,IL34,PDGFD,SH3BP2,Kaplan-Meier survival analysis showed that the survival prognosis of the low-risk group was significantly better than that of the high-risk group (P＜0.001).The network regulation analysis showed of 16 TFs and 7 IRGs differentially expressed ENDRA,IGF1,RAC3 as the core of the regulatory network.Riskscore value based on IRGs reflect a variety of immune cell infiltration related conditions.Conclusion:Our immune-risk model can be used to predict survival prognosis in patients with BC,and further studies have found multiple immune cell infiltration in BC,which may help expand the scope of application of immunotherapy.

References:

［1］ 贺宇彤,李道娟,梁迪,等.2014年中国膀胱癌发病和死亡分析［J］.中华肿瘤杂志,2018,40(09):647-652. HE YT，LI DJ,LIANG D,et al.Incidence and mortality of bladder cancer in China,2014［J］.Chinese Journal of Cancer,2018,40(09):647-652.
[2] NIH NCI:Surveillance,epidemiology,and end results program［EB/OL］.(2020-02-01)［2020-04-23］.https://seer.cancer.gov/statfacts/html/urinb.html.
[3] PARE L,PASCUAL T,SEGUI E,et al.Association between PD1 mRNA and response to anti-PD1 monotherapy across multiple cancer types ［J］.Ann Oncol,2018,29(10):2121-2128.
[4] VILLARUZ LC,ANCEVSKI HUNTER K,KURLAND BF,et al.Comparison of PD-L1 immunohistochemistry assays and response to PD-1/L1 inhibitors in advanced non-small-cell lung cancer in clinical practice ［J］.Histopathology,2019,74(2):269-275.
[5] WEST H,MCCLEOD M,HUSSEIN M,et al.Atezolizumab in combination with carboplatin plus nab-paclitaxel chemotherapy compared with chemotherapy alone as first-line treatment for metastatic non-squamous non-small-cell lung cancer (IMpower130):A multicentre,randomised,open-label,phase 3 trial ［J］.The Lancet Oncology,2019,20(7):924-937.
[6] VINAYAK S,TOLANEY SM,SCHWARTZBERG L,et al.Open-label clinical trial of niraparib combined with pembrolizumab for treatment of advanced or metastatic triple-negative breast cancer ［J］.JAMA Oncol,2019,5(8):1132-1140.
[7] MARABELLE A,LE DT,ASCIERTO PA,et al.Efficacy of pembrolizumab in patients with noncolorectal high microsatellite instability/mismatch pepair-deficient cancer:Results from the phase II KEYNOTE-158 study ［J］.J Clin Oncol,2020,38(1):1-10.
[8] KALBASI A,RIBAS A.Tumour-intrinsic resistance to immune checkpoint blockade ［J］.Nat Rev Immunol,2020,20(1):25-39.
[9]YANG S,LIU T,NAN H,et al.Comprehensive analysis of prognostic immune-related genes in the tumor microenvironment of cutaneous melanoma ［J］.Journal of Cellular Physiology,2019,37:54-62.
[10] ZHANG JX,SONG W,CHEN ZH,et al.Prognostic and predictive value of a microRNA signature in stage II colon cancer:A microRNA expression analysis ［J］.The Lancet Oncology,2013,14(13):1295-1306.
[11] NEWMAN AM,LIU CL,GREEN MR,et al.Robust enumeration of cell subsets from tissue expression profiles ［J］.Nature Methods,2015,12(5):453-457.
[12] WANG L,MO Q,WANG J.MIrExpress:A database for gene coexpression correlation in immune cells based on mutual information and pearson correlation ［J］.Journal of Immunology Research,2015,2015:140819.
[13] 翟建坡,刘宁,王海,等.改良GC方案与传统GC方案治疗尿路上皮癌疗效及毒副反应的对比［J］.现代肿瘤医学,2018,26(12):1881-1884. ZHAI JP，LIU N,WANG H,et al.Comparative of efficacy and toxicity between modified GC regimen and conventional GC regimen in chemotherapy of urothelial carcinoma［J］.Modern Oncology,2018,26(12):1881-1884.
[14] 辛士永,李亮亮,吴硕,等.吉西他滨联合卡介苗膀胱灌注预防高危非肌层浸润性膀胱癌术后复发的效果［J］.中国老年学杂志,2019,39(05):1064-1068. XIN SY,LI LL,WU S,et al.Evaluation of relapse prevention of bladder perfusion with gemcitabine and BCG after transurethral resection of bladder tumor of high-risk nonmuscle invasive bladder cancer ［J］.Chinese Journal of Gerontology,2019,39(05):1064-1068.
[15] GUBENS MA,DAVIES M.NCCN guidelines updates:New immunotherapy strategies for improving outcomes in non-small cell lung cancer［J］.J Natl Compr Canc Netw,2019,17(5.5):574-578.
[16] CAMIDGE DR,DOEBELE RC,KERR KM.Comparing and contrasting predictive biomarkers for immunotherapy and targeted therapy of NSCLC ［J］.Nature Reviews Clinical Oncology,2019,16(6):341-355.
[17] PETITPREZ F,DE RA,KEUNG EZ,et al.B cells are associated with survival and immunotherapy response in sarcoma［J］.Nature,2020,577(7791):556-560.
[18] VAN DER WILLIK K D,KOPPELMANS V,HAUPTMANN M,et al.Inflammation markers and cognitive performance in breast cancer survivors 20 years after completion of chemotherapy:A cohort study ［J］.Breast Cancer Research,2018,20(1):135-141.
[19] XIE T,LIU B,DAI CG,et al.Glioma stem cells reconstruct similar immunoinflammatory microenvironment in different transplant sites and induce malignant transformation of tumor microenvironment cells ［J］.Journal of Cancer Research and Clinical Oncology,2019,145(2):321-328.
[20] WEBER R,MEISTER M,MULEY T,et al.Pathways regulating the expression of the immunomodulatory protein glycodelin in nonsmall cell lung cancer ［J］.International Journal of Oncology,2019,54(2):515-526.
[21] SERRANO-CANDELAS E,AINSUA-ENRICH E,NAVINES-FERRER A,et al.Silencing of adaptor protein SH3BP2 reduces KIT/PDGFRA receptors expression and impairs gastrointestinal stromal tumors growth ［J］.Molecular Oncology,2018,12(8):1383-1397.
[22] OLSEN RS,DIMBERG J,GEFFERS R,et al.Possible role and therapeutic target of PDGF-D signalling in colorectal cancer ［J］.Cancer Investigation,2019,37(2):99-112.
[23] LEISCHING G,COLE V,ALI AT,et al.OAS1,OAS2 and OAS3 restrict intracellular M.tb replication and enhance cytokine secretion ［J］.International Journal of Infectious Diseases,2019,80s:s77-s84.
[24] FOUAD H,SALEM H,ELLAKWA DE,et al.MMP-2 and MMP-9 as prognostic markers for the early detection of urinary bladder cancer ［J］.Journal of Biochemical and Molecular Toxicology,2019,33(4):e22275.
[25] LEE H,KIM K,WOO J,et al.Quantitative proteomic analysis identifies AHNAK (neuroblast differentiation-associated protein AHNAK) as a novel candidate biomarker for bladder urothelial carcinoma diagnosis by liquid-based cytology ［J］.Molecular & Cellular Proteomics,2018,17(9):1788-1802.
[26] EFTEKHARI R,DE LIMA SG,LIU Y,et al.Microenvironment proteinases,proteinase-activated receptor regulation,cancer and inflammation ［J］.Biological Chemistry,2018,399(9):1023-1039.
[27] GULLO I,OLIVEIRA P,ATHELOGOU M,et al.New insights into the inflamed tumor immune microenvironment of gastric cancer with lymphoid stroma:From morphology and digital analysis to gene expression ［J］.Gastric Cancer,2019,22(1):77-90.
[28] SLOWIKOWSKI K,WEI K,BRENNER MB,et al.Functional genomics of stromal cells in chronic inflammatory diseases ［J］.Current Opinion in Rheumatology,2018,30(1):65-71.
[29] YEONG J,LIM JCT,LEE B,et al.Prognostic value of CD8+ PD-1+ immune infiltrates and PDCD1 gene expression in triple negative breast cancer ［J］.Journal for Immunotherapy of Cancer,2019,7(1):34-41.
[30] PRAT A,NAVARRO A,PARE L,et al.Immuner related gene expression profiling after PD-1 blockade in non-small cell lung carcinoma,head and neck squamous cell carcinoma,and melanoma ［J］.Cancer Research,2017,77(13):3540-3550.
[31] SUNAKAWA Y,YANG D,CAO S,et al.Immune-related genes to dominate neutrophil-lymphocyte ratio (NLR) associated with survival of cetuximab treatment in metastatic colorectal cancer ［J］.Clinical Colorectal Cancer,2018,17(4):e741-e749.
[32] CHEN S,ZHANG N,SHAO J,et al.Multi-omics perspective on the tumor microenvironment based on PD-L1 and CD8 T-cell infiltration in urothelial cancer ［J］.Journal of Cancer,2019,10(3):697-707.

Memo

Memo:
广西自然科学基金项目(编号： 2018GXNSFAA281270)；广西卫生健康委员会科研课题项目（编号：Z20190502）
Last Update: 2021-01-29