目的：探讨同源盒C8（Homeobox C8,HOXC8）在结肠癌中的表达及临床意义。方法：结合临床数据分析TCGA数据库及GEO数据集中HOXC8 mRNA在结肠癌中的表达。通过免疫组织化学检测100例结肠癌患者组织样本中的HOXC8蛋白水平,并分析其与临床病理参数的相关性。使用单变量和多变量Cox风险回归模型以及Kaplan-Meier来评估HOXC8在结肠癌中的预后价值。GEPIA数据库用于评估HOXC8和免疫标志物的相关性。结果：根据数据库分析和患者组织样本的检测,我们发现HOXC8在结肠癌组织中表达增加,mRNA表达水平及蛋白水平与肿瘤状态显著相关。基于TCGA数据集及GEO GSE39582数据集我们使用Cox回归分析发现HOXC8是影响结肠癌患者预后的独立危险因素,其中,在TCGA数据集中R=2.20,95% CI 1.33~3.66,P=0.002,在GEO GSE39582数据集中,HR=1.58,95% CI：1.02~2.45,P= 0.039。我们还研究了HOXC8在肿瘤-免疫相互作用中的潜在作用,发现HOXC8可能与结肠癌的多种免疫细胞显著相关。结论：HOXC8在结肠癌中表达上调,既具有作为预后潜在的指标又具有作为结肠癌免疫相关治疗靶标的潜力。
Abstract
Objective To investigate the expression and clinical significance of Homeobox C8 (HOXC8) in colon cancer (CC) . Methods The Cancer Genome Atlas (TCGA) database and GEO database were used to analyze HOXC8 mRNA expression in CC tissues. A total of 100 patients with CC tissue specimens and clinicopathological data were collected from Chongqing Medical University First Affiliated Hospital, and HOXC8 protein was detected by immunohistochemistry. Moreover, the association between HOXC8 expression and clinicopathological characteristics was analyzed. Univariate and multivariate Cox regression models and Kaplan-Meier were used to evaluate the prognostic value of HOXC8 in CC. The GEPIA database was used to evaluate the correlation between HOXC8 and immune cell biomarkers. Results Multi databases analysis and detection of patient tissue samples showed that the mRNA and protein expression level of HOXC8 is increased in cancer tissue (P<0.05, P<0.001) . In addition, the high expression of HOXC8 is related to poor overall survival rate (In TCGA data set, P<0.001; In GEO GSE39582 data set, P=0.008) . Cox regression analysis suggests that HOXC8 is an independent risk factor affecting the prognosis of patients with CC (In TCGA data set, P=0.002; In GEO GSE39582 data set, P= 0.039) . We also studied the potential role of HOXC8 in tumor-immune interactions, and found that HOXC8 may be significantly associated with multiple immune cells in colon cancer (P< 0.001) . Conclusion Our study showed that the expression of HOXC8 is up-regulated in CC, and revealed the prognostic potential of HOXC8 in CC and its potential as an immune-related therapeutic target for CC.
关键词
结肠癌 /
HOXC8 /
预后 /
肿瘤免疫
Key words
colon cancer /
HOXC8 /
prognosis /
immunotherapy
{{custom_sec.title}}
{{custom_sec.title}}
{{custom_sec.content}}
参考文献
[1] SIEGEL RL, MILLER KD, JEMAL A.Cancer statistics, 2020[J]. CA Cancer J Clin, 2020, 70(1) : 7-30.
[2] ANGELL HK, BRUNI D, BARRETT JC, et al.The Immunoscore: Colon Cancer and Beyond[J]. Clin Cancer Res, 2020, 26(2) : 332-339.
[3] ALSAAB HO, SAU S, ALZHRANI R, et al.PD-1 and PD-L1 Checkpoint Signaling Inhibition for Cancer Immunotherapy: Mechanism, Combinations, and Clinical Outcome[J]. Front Pharmacol, 2017, 8: 561.
[4] PEARSON JC, LEMONS D, MCGINNIS W.Modulating Hox gene functions during animal body patterning[J]. Nat Rev Genet, 2005, 6(12) : 893-904.
[5] XU P, ZHANG X, NI W, et al.Upregulated HOXC8 Expression Is Associated with Poor Prognosis and Oxaliplatin Resistance in Hepatocellular Carcinoma[J]. Dig Dis Sci, 2015, 60(11) : 3351-3363.
[6] GONG C, ZOU J, ZHANG M, et al.Upregulation of MGP by HOXC8 promotes the proliferation, migration, and EMT processes of triple-negative breast cancer[J]. Mol Carcinog, 2019, 58(10) : 1863-1875.
[7] TSAI CY, LIAO JB, LEE YC, et al. HOXC8 mediates osteopontin expression in gastric cancer cells [J]. J Cancer, 2023, 21; 14(13) : 2552-2561.
[8] X SHI, X YANG, D CHEN, et al.Smad1 interacts with homeobox DNA-binding proteins in bone morphogenetic protein signaling[J]. J Biol Chem, 1999, 274(19) : 13711-7.
[9] QIAN LI, YIFAN WANG, WEIJUAN JIA, et al.Low-Dose Anti-Angiogenic Therapy Sensitizes Breast Cancer to PD-1 Blockade[J]. Clin Cancer Res, 2020, 26(7) : 1712-1724.
[10] GEORGES R, ADWAN H, ZHIVKOVA M, et al.Regulation of osteopontin and related proteins in rat CC531 colorectal cancer cells[J]. Int J Oncol, 2010, 37(2) : 249-256.
[11] VIVIAN J, RAO AA, NOTHAFT FA, et al.Musselman-Brown A et al. Toil enables reproducible, open source, big biomedical data analyses[J]. Nat Biotechnol, 2017, 35(4) : 314-316.
[12] LI T, FAN J, WANG B, et al.TIMER: A Web Server for Comprehensive Analysis of Tumor-Infiltrating Immune Cells[J]. Cancer Res, 2017, 77(21) : e108-e110.
[13] DAMMANN K, KHARE V, HARPAIN F, et al.PAK1 promotes intestinal tumor initiation[J]. Cancer Prev Res (Phila) , 2015, 8(11) : 1093-1101.
[14] SUBRAMANIAN A, TAMAYO P, MOOTHA VK, et al.Gene set enrichment analysis: a knowledge-based approach for interpreting genome-wide expression profiles[J]. Proc Natl Acad Sci U S A, 2005, 102(43) : 15545-15550.
[15] NARAYANAN S, KAWAGUCHI T, YAN L, et al.Cytolytic Activity Score to Assess Anticancer Immunity in Colorectal Cancer[J]. Ann Surg Oncol, 2018, 25(8) : 2323-2331.
[16] WEI J, LONG L, YANG K, et al.Autophagy enforces functional integrity of regulatory T cells by coupling environmental cues and metabolic homeostasis[J]. Nat Immunol, 2016, 17(3) : 277-285.
[17] WCULEK SK, CUETO FJ, MUJAL AM, et al.Dendritic cells in cancer immunology and immunotherapy[J]. Nat Rev Immunol, 2020, 20(1) : 7-24.
[18] 宮甜甜, 黄少刚, 张玥, 等. 巨噬细胞的极化及功能调控[J]. 解剖学报, 2017, 48(1) : 106-109.
[19] BERCOVICI N, GUERIN MV, TRAUTMANN A, et al.The Remarkable Plasticity of Macrophages: A Chance to Fight Cancer[J]. Front Immunol, 2019, 10: 1563.
[20] LAN J, SUN L, XU F, et al.M2 Macrophage-Derived Exosomes Promote Cell Migration and Invasion in Colon Cancer[J]. Cancer Res, 2019, 79(1) : 146-158.
[21] AXLUND SD, LAMBERT JR, NORDEEN SK.HOXC8 inhibits androgen receptor signaling in human prostate cancer cells by inhibiting SRC-3 recruitment to direct androgen target genes[J]. Mol Cancer Res, 2010, 8(12) : 1643-1655.
基金
湖南省卫生健康委科研计划项目“结肠癌免疫微环境中同源盒 C8 HOXC8与致瘤性免疫浸润的相关性”（202203103412）; 邵阳市科技计划项目“结肠癌细胞溶解活性相关基因预后模型在免疫治疗疗效的预测作用”（2021NS055）,“F-Box蛋白17 FBXO17的泛癌研究及验证”（2022NS449）
PDF(3026 KB)
