QI Rongxuan, LIU Geliang, MU Junfang, LI Chenlong, LI Yuan, HE Peifeng, YU Qi. Screening of immune-related genes and establishment of prognostic model for colon cancer[J]. Journal of Clinical Medicine in Practice, 2023, 27(14): 63-71, 77. DOI: 10.7619/jcmp.20231576
Citation: QI Rongxuan, LIU Geliang, MU Junfang, LI Chenlong, LI Yuan, HE Peifeng, YU Qi. Screening of immune-related genes and establishment of prognostic model for colon cancer[J]. Journal of Clinical Medicine in Practice, 2023, 27(14): 63-71, 77. DOI: 10.7619/jcmp.20231576

Screening of immune-related genes and establishment of prognostic model for colon cancer

More Information
  • Received Date: May 15, 2023
  • Revised Date: June 23, 2023
  • Available Online: July 30, 2023
  • Objective 

    To screen key prognosis-related immune genes(KIGs) in colon cancer(CC) and construct immune-related prognostic model.

    Methods 

    The gene expression data and clinical data of CC patients were downloaded from the Cancer Genome Atlas (TCGA), differential expressed genes (DEGs) were screened based on immune typing, and the intersection of DEGs and immune genes of ImmPort database was used to obtain differentially expressed immune genes (DEIGs). Univariate Cox analysis and Lasso-Cox analysis were used to screen KIGs to establish immune-related prognostic models. Next, the predictive performance of the prognostic model was verified. The correlations of risk score with clinical features, immune infiltrating cells, tumor mutation burden, and microsatellite instability were analyzed. Independent prognostic factors of CC were screened by univariate and multivariate Cox analysis, and a nomogram related to overall survival rate (OS) was constructed to predict the overall survival rate of CC patients.

    Results 

    A total of 1, 439 DEGs were screened out based on immune typing, and 379 DEIGs were obtained by the intersection of DEGs and immune genes of ImmPort database. A total of 12 KIGs were screened out by univariate Cox analysis and Lasso-Cox analysis, and an immune-related prognostic model was constructed. There was a significant difference in OS between high-risk score patients(high-risk group) and low-risk score patients (low-risk group)(P < 0.05). The area under the receiver operating characteristic curve (AUC) for 1-, 3- and 5-year were 0.735, 0.725 and 0.699, respectively, which showed that the model had a good predictive effect. There were significant differences in risk scores of patients with different disease stages and different TNM stages (P < 0.05); KIGs was correlated with numerous immune infiltrating cells (P < 0.05); micro-satellite instability was greater in the high-risk group than in the low-risk group. Univariate and multivariate Cox regression analysis showed that risk score was an independent prognostic factor for CC (P < 0.001), and the further constructed nomogram had good predictive power and accuracy for the survival status of CC patients.

    Conclusion 

    An immune-related prognostic model based on 12 KIGs is constructed in the study, and a nomogram is developed to predict overall survival in CC patients, which could help physicians make individualized treatment decisions.

  • [1]
    SUNG H, FERLAY J, SIEGEL R L, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries[J]. CA Cancer J Clin, 2021, 71(3): 209-249. doi: 10.3322/caac.21660
    [2]
    陈卓林, 龚时文, 黄东, 等. 新辅助化疗对结直肠癌肝转移患者术前的临床效果[J]. 中国肿瘤临床与康复, 2019, 26(10): 1200-1203. https://www.cnki.com.cn/Article/CJFDTOTAL-ZGZK201910014.htm
    [3]
    ANGELL H K, BRUNI D, BARRETT J C, et al. The immunoscore: colon cancer and beyond[J]. Clin Cancer Res, 2020, 26(2): 332-339. doi: 10.1158/1078-0432.CCR-18-1851
    [4]
    吴介恒, 杨安钢, 温伟红. PD-1/PD-L1参与肿瘤免疫逃逸的研究进展[J]. 细胞与分子免疫学杂志, 2014, 30(7): 777-780. https://www.cnki.com.cn/Article/CJFDTOTAL-XBFM201407028.htm
    [5]
    TAURIELLO D V F, PALOMO-PONCE S, STORK D, et al. TGFβ drives immune evasion in genetically reconstituted colon cancer metastasis[J]. Nature, 2018, 554(7693): 538-543. doi: 10.1038/nature25492
    [6]
    O′CONNELL J, BENNETT M W, NALLY K, et al. Altered mechanisms of apoptosis in colon cancer: Fas resistance and counterattack in the tumor-immune conflict[J]. Ann N Y Acad Sci, 2000, 910: 178-192; discussion 193-195.
    [7]
    刘革新, 刘盼, 陈维顺. 胃癌免疫相关LncRNA预后风险模型的建立与分析[J]. 现代消化及介入诊疗, 2021, 26(7): 849-853. doi: 10.3969/j.issn.1672-2159.2021.07.011
    [8]
    WANG Z Q, ZHU L P, LI L, et al. Identification of an immune gene-associated prognostic signature in patients with bladder cancer[J]. Cancer Gene Ther, 2022, 29(5): 494-504. doi: 10.1038/s41417-022-00438-5
    [9]
    LEI X, LEI Y, LI J K, et al. Immune cells within the tumor microenvironment: biological functions and roles in cancer immunotherapy[J]. Cancer Lett, 2020, 470: 126-133. doi: 10.1016/j.canlet.2019.11.009
    [10]
    GALON J, FRIDMAN W H, PAGE S F. The adaptive immunologic microenvironment in colorectal cancer: a novel perspective[J]. Cancer Res, 2007, 67(5): 1883-1886. doi: 10.1158/0008-5472.CAN-06-4806
    [11]
    SHEN C, LUO C, XU Z J, et al. Molecular patterns based on immunogenomic signatures stratify the prognosis of colon cancer[J]. Front Bioeng Biotechnol, 2022, 10: 820092. doi: 10.3389/fbioe.2022.820092
    [12]
    SLATTERY M L, LUNDGREEN A, KADLUBAR S A, et al. JAK/STAT/SOCS-signaling pathway and colon and rectal cancer[J]. Mol Carcinog, 2013, 52(2): 155-166. doi: 10.1002/mc.21841
    [13]
    DING H, YANG X, WEI Y Z. Fusion proteins of NKG2D/NKG2DL in cancer immunotherapy[J]. Int J Mol Sci, 2018, 19(1): 177. doi: 10.3390/ijms19010177
    [14]
    LU H M, MA Y C, WANG M Y, et al. B7-H3 confers resistance to Vγ9Vδ2 T cell-mediated cytotoxicity in human colon cancer cells via the STAT3/ULBP2 axis[J]. Cancer Immunol Immunother, 2021, 70(5): 1213-1226. doi: 10.1007/s00262-020-02771-w
    [15]
    ZHENG X, LIU R, ZHOU C C, et al. ANGPTL4-mediated promotion of glycolysis facilitates the colonization of Fusobacterium nucleatum in colorectal cancer[J]. Cancer Res, 2021, 81(24): 6157-6170. doi: 10.1158/0008-5472.CAN-21-2273
    [16]
    KIM S H, PARK Y Y, KIM S W, et al. ANGPTL4 induction by prostaglandin E2 under hypoxic conditions promotes colorectal cancer progression[J]. Cancer Res, 2011, 71(22): 7010-7020. doi: 10.1158/0008-5472.CAN-11-1262
    [17]
    LU X J. Structure and function of ligand CX3CL1 and its receptor CX3CR1 in cancer[J]. Curr Med Chem, 2022, 29(41): 6228-6246. doi: 10.2174/0929867329666220629140540
    [18]
    ZHENG J, YANG M, SHAO J H, et al. Chemokine receptor CX3CR1 contributes to macrophage survival in tumor metastasis[J]. Mol Cancer, 2013, 12(1): 141. doi: 10.1186/1476-4598-12-141
    [19]
    OLSEN R S, NIJM J, ANDERSSON R E, et al. Circulating inflammatory factors associated with worse long-term prognosis in colorectal cancer[J]. World J Gastroenterol, 2017, 23(34): 6212-6219. doi: 10.3748/wjg.v23.i34.6212
    [20]
    LIU S J, WU D, FAN Z Y, et al. FABP4 in obesity-associated carcinogenesis: novel insights into mechanisms and therapeutic implications[J]. Front Mol Biosci, 2022, 9: 973955. doi: 10.3389/fmolb.2022.973955
    [21]
    TIAN W Y, ZHANG W J, ZHANG Y, et al. FABP4 promotes invasion and metastasis of colon cancer by regulating fatty acid transport[J]. Cancer Cell Int, 2020, 20: 512. doi: 10.1186/s12935-020-01582-4
    [22]
    HE X F, CHEN H J, ZHONG X Y, et al. BST2 induced macrophage M2 polarization to promote the progression of colorectal cancer[J]. Int J Biol Sci, 2023, 19(1): 331-345. doi: 10.7150/ijbs.72538
    [23]
    FOLLI C, CALDERONE V, RAMAZZINA I, et al. Ligand binding and structural analysis of a human putative cellular retinol-binding protein[J]. J Biol Chem, 2002, 277(44): 41970-41977. doi: 10.1074/jbc.M207124200
    [24]
    HUANG X X, KE K, JIN W W, et al. Identification of genes related to 5-fluorouracil based chemotherapy for colorectal cancer[J]. Front Immunol, 2022, 13: 887048. doi: 10.3389/fimmu.2022.887048
    [25]
    ELMASRY M, BRANDL L, ENGEL J, et al. RBP7 is a clinically prognostic biomarker and linked to tumor invasion and EMT in colon cancer[J]. J Cancer, 2019, 10(20): 4883-4891. doi: 10.7150/jca.35180
    [26]
    STREEL G D, LUCAS S. Targeting immunosuppression by TGF-β1 for cancer immunotherapy[J]. Biochem Pharmacol, 2021, 192: 114697. doi: 10.1016/j.bcp.2021.114697
    [27]
    JIN Q N, JIN X, LIU T, et al. A disintegrin and metalloproteinase 8 induced epithelial-mesenchymal transition to promote the invasion of colon cancer cells via TGF-β/Smad2/3 signalling pathway[J]. J Cell Mol Med, 2020, 24(22): 13058-13069. doi: 10.1111/jcmm.15907
    [28]
    GULUBOVA M, ALEKSANDROVA E, VLAYKOVA T. Promoter polymorphisms in TGFB1 and IL10 genes influence tumor dendritic cells infiltration, development and prognosis of colorectal cancer[J]. J Gene Med, 2018, 20(2/3): e3005.
    [29]
    CHEN W, CHEN Y W, SU J, et al. CaMKII mediates TGFβ1-induced fibroblasts activation and its cross talk with colon cancer cells[J]. Dig Dis Sci, 2022, 67(1): 134-145. doi: 10.1007/s10620-021-06847-0
    [30]
    陈清梅, 陈睿, 邓阳. 肝细胞癌组织中APOBEC3s类胞苷脱氨酶基因家族成员的表达观察[J]. 山东医药, 2018, 58(47): 15-19. doi: 10.3969/j.issn.1002-266X.2018.47.004
    [31]
    BOCCARELLI A, DEL BUONO N, ESPOSITO F. Colorectal cancer in Crohn's disease evaluated with genes belonging to fibroblasts of the intestinal mucosa selected by NMF[J]. Pathol Res Pract, 2022, 229: 153728. doi: 10.1016/j.prp.2021.153728
    [32]
    PICARD E, VERSCHOOR C P, MA G W, et al. Relationships between immune landscapes, genetic subtypes and responses to immunotherapy in colorectal cancer[J]. Front Immunol, 2020, 11: 369. doi: 10.3389/fimmu.2020.00369
    [33]
    张娟学, 叶玉伟, 张军, 等. 免疫检查点抑制剂治疗结直肠肿瘤相关研究进展[J]. 现代消化及介入诊疗, 2022, 27(6): 781-785. https://www.cnki.com.cn/Article/CJFDTOTAL-XDXH202206027.htm
    [34]
    CHEN J J, APIZI A, WANG L, et al. TCGA database analysis of the tumor mutation burden and its clinical significance in colon cancer[J]. J Gastrointest Oncol, 2021, 12(5): 2244-2259. doi: 10.21037/jgo-21-661
    [35]
    SAMSTEIN R M, LEE C H, SHOUSHTARI A N, et al. Tumor mutational load predicts survival after immunotherapy across multiple cancer types[J]. Nat Genet, 2019, 51(2): 202-206. doi: 10.1038/s41588-018-0312-8
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