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.
[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.
2023, Vol. 20 
