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Journal of Peking University (Health Sciences) ›› 2022, Vol. 54 ›› Issue (2): 203-208. doi: 10.19723/j.issn.1671-167X.2022.02.001

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Establishment of a prediction model for colorectal cancer immune cell infiltration based on the cancer genome atlas (TCGA) database

DING Ting-ting,ZENG Chu-xiong,HU Li-na,YU Ming-hua()   

  1. Department of Oncology, Shanghai Pudong Hospital, Pudong Hospital Affiliated to Fudan University, Shanghai 201399, China
  • Received:2021-11-18 Online:2022-04-18 Published:2022-04-13
  • Contact: Ming-hua YU E-mail:ymh3011@163.com
  • Supported by:
    Pudong New Area Science and Technology Development Fund(PKJ2018-Y33);Shanghai Pudong New Area Health System Young Medical Talents Training Program Project(PWRq2021-21)

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Abstract:

Objective: To study the correlation between immune cell infiltration in colorectal cancer tissue and clinical prognosis and to explore the levels of some immune cell genes for predicting the prognosis of patients with glioma colorectal cancer. Methods: In this study, we extracted colorectal cancer data from the cancer genome atlas (TCGA). Based on a deconvolution algorithm (called CIBERSORT) and clinically annotated expression profiles, the analysis assessed the infiltration patterns of 22 immune cells in colorectal cancer tissue to determine the association between each cell type and survival. Differences in five-year survival rate effectively illustrate the clinical prognostic value of each immune cell proportion in colorectal cancer, using a bar graph, correlation-based heatmap to represent the proportion of immune cells in each colorectal cancer sample. Results: A total of 473 colorectal cancer tissues and 41 normal control tissues were extracted from the TCGA database, and the comparative analysis showed that there were differences in the proportion of various TIICs in colorectal cancer tissues, which could characterize individual differences and have prognostic value. Among the cell subsets studied, the proportions of memory B cells, plasma cells, CD4+ T cells, natural killer (NK) cells, M0 macrophages, M2 macrophages, and activated mast cells were significantly different between normal and cancer tissues. Resting NK cells, CD8+ T cells, and plasma cells were associated with T phase, activated dendritic cells were associated with N phase, and eosinophils, M1 macrophages, and activated mast cells were associated with M phase. Survival analysis showed that activated dendritic cells were positively associated with five-year survival rate in colorectal cancer patients. Naive CD4+ T cells were inversely associated with five-year survival rate. Conclusion: There are different degrees of immune cell infiltration in colorectal cancer tissues, and these differences may be important determinants of prognosis and treatment response. We conducted a new gene expression-based study of immune cell subtype levels and prognosis in colorectal cancer, which has potential clinical prognostic value in colorectal cancer patients.

Key words: Lymphocytes, tumor-infiltrating, Colorectal neoplasms, Genetic databases, Nomogram, Clinicopathological characteristics

CLC Number: 

  • R730.51

Table 1

General clinical characteristics of colorectal cancer patients in the TCGA database"

Characteristics n (%)
Gender
Male 238 (50.4)
Female 235 (49.6)
Vital status
Living 88 (18.6)
Deceased 385 (81.4)
Clinical stage
StageⅠ-Ⅱ 254 (53.7)
Stage Ⅲ-Ⅳ 219 (46.3)
T stage
T1 10 (2.1)
T2 77 (16.3)
T3 308 (65.1)
T4 78 (16.5)
N stage
N0 270 (57.1)
N1 103 (21.8)
N2 100 (21.1)
M stage
M0 334 (70.6)
M1 62 (23.1)
Mx 77 (16.3)

Figure 1

The proportion of immune cells in each colorectal cancer and normal tissue sample Different colors represent different immune cells, and the length of the bars in the bar graph represents the level of immune cell populations."

Figure 2

Correlation matrix for all 22 TIICs proportions Some immune cells were negatively related, represented in blue, and others were positively related, represented in red. The darker the colour, the higher the correlation was."

Figure 3

Relationship between TIICs and TNM stage and clinical stage of colorectal cancer"

Figure 4

Survival curves of specific immune cell populations with significantly correlated five-year survival rate A, activated dendritic cells; B, naïve CD4+T cells."

[1] Siegel RL, Miller KD, Fedewa SA, et al. Colorectal cancer statistics, 2017[J]. CA Cancer J Clin, 2017, 67(3):177-193.
doi: 10.3322/caac.21395
[2] Shibutani M, Maeda K, Nagahara H, et al. Tumor-infiltrating lymphocytes predict the chemotherapeutic outcomes in patients with stage Ⅳ colorectal cancer[J]. In Vivo, 2018, 32(1):151-158.
[3] Guinney J, Dienstmann R, Wang X, et al. The consensus mole-cular subtypes of colorectal cancer[J]. Nat Med, 2015, 21(11):1350-1356.
doi: 10.1038/nm.3967 pmid: 26457759
[4] Church J. Molecular genetics of colorectal cancer[J]. Sem Colon Rectal Surg, 2016, 27(4):172-175.
doi: 10.1053/j.scrs.2016.04.013
[5] Bremnes RM, Al-Shibli K, Donnem T, et al. The role of tumor-infiltrating immune cells and chronic inflammation at the tumor site on cancer development, progression, and prognosis: Emphasis on non-small cell lung cancer[J]. J Thorac Oncol, 2011, 6(4):824-833.
doi: 10.1097/JTO.0b013e3182037b76 pmid: 21173711
[6] Mao X, Xu J, Wang W, et al. Crosstalk between cancer-associated fibroblasts and immune cells in the tumor microenvironment: New findings and future perspectives[J]. Mol Cancer, 2021, 20(1):131-142.
doi: 10.1186/s12943-021-01428-1
[7] Baxevanis CN, Papamichail M, Perez SA. Immune classification of colorectal cancer patients: Impressive but how complete?[J]. Expert Opin Biol Ther, 2013, 13(4):517-526.
doi: 10.1517/14712598.2013.751971
[8] Grizzi F, Basso G, Borroni EM, et al. Evolving notions on immune response in colorectal cancer and their implications for biomarker developmentc[J]. Inflamm Res, 2018, 67(5):375-389.
doi: 10.1007/s00011-017-1128-1 pmid: 29322204
[9] Newman AM, Liu CL, Green MR, et al. Robust enumeration of cell subsets from tissue expression profiles[J]. Nat Methods, 2015, 12(5):453-457.
doi: 10.1038/nmeth.3337 pmid: 25822800
[10] Liu X, Wu S, Yang Y, et al. The prognostic landscape of tumor-infiltrating immune cell and immunomodulators in lung cancer[J]. Biomed Pharmacother, 2017, 95:55-61.
doi: 10.1016/j.biopha.2017.08.003
[11] Quail DF, Joyce JA. Microenvironmental regulation of tumor progression and metastasis[J]. Nat Med, 2013, 19(11):1423-1437.
doi: 10.1038/nm.3394
[12] Klemm F, Joyce JA. Microenvironmental regulation of therapeutic response in cancer[J]. Trends Cell Biol, 2015, 25(4):198-213.
doi: 10.1016/j.tcb.2014.11.006
[13] Anitei MG, Zeitoun G, Mlecnik B, et al. Prognostic and predictive values of the immunoscore in patients with rectal cancer[J]. Clin Cancer Res, 2014, 20(7):1891-1899.
doi: 10.1158/1078-0432.CCR-13-2830
[14] Huh JW, Lee JH, Kim HR. Prognostic significance of tumorinfiltrating lymphocytes for patients with colorectal cancer[J]. Arch Surg, 2012, 147(4):366-372.
doi: 10.1001/archsurg.2012.35
[15] Karpinski P, Rossowska J, Sasiadek MM. Immunological landscape of consensus clusters in colorectal cancer[J]. Oncotarget, 2017, 8(62):105299-105311.
doi: 10.18632/oncotarget.v8i62
[16] Mirjolet C, Charon-Barra C, Ladoire S, et al. Tumor lymphocyte immune response to preoperative radiotherapy in locally advanced rectal cancer: The LYMPHOREC study[J]. Oncoimmunology, 2018, 7(3):e1396402.
doi: 10.1080/2162402X.2017.1396402
[17] Galon J, Costes A, Sanchez-Cabo F, et al. Type, density, and location of immune cells within human colorectal tumors predict clinical outcome[J]. Science, 2006, 313(5759):1960-1964.
doi: 10.1126/science.1129139
[18] Klintrup K, Makinen JM, Kauppila S, et al. Inflammation and prognosis in colorectal cancer[J]. Eur J Cancer, 2005, 41(17):2645-2654.
doi: 10.1016/j.ejca.2005.07.017 pmid: 16239109
[19] 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.
doi: 10.1158/0008-5472.CAN-17-0307
[20] Pagès F, Mlecnik B, Marliot F, et al. International validation of the consensus immunoscore for the classification of colon cancer: A prognostic and accuracy study[J]. Lancet, 2018, 391(10135):2128-2139.
doi: 10.1016/S0140-6736(18)30789-X
[21] Steinman RM. Decisions about dendritic cells: Past, present, and future[J/OL]. Annu Rev Immunol, 2012, 30:1-22. doi: 10.1146/annurevimmunol-100311-102839.
doi: 10.1146/annurevimmunol-100311-102839
[22] Shimizu K, Kotera Y, Aruga A, et al. Postoperative dendritic cell vaccine plus activated T-cell transfer improves the survival of patients with invasive hepatocellular carcinoma[J]. Hum Vaccin Immunother, 2014, 10(4):970-976.
doi: 10.4161/hv.27678
[23] Pagès F, Kirilovsky A, Mlecnik B, et al. In situ cytotoxic and memory T cells predict outcome in patients with early-stage colorectal cancer[J]. J Clin Oncol, 2009, 27(35):5944-5951.
[24] Gannon PO, Baumgaertner P, Huber A, et al. Rapid and continued T-cell differentiation into long-term effector and memory stem cells in vaccinated melanoma patients[J]. Clin Cancer Res, 2017, 23(13):3285-3296.
doi: 10.1158/1078-0432.CCR-16-1708
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