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. 2019 Mar;7(3):e504.
doi: 10.1002/mgg3.504. Epub 2019 Jan 9.

A comprehensive study of immunology repertoires in both preoperative stage and postoperative stage in patients with colorectal cancer

Xicheng Liu  1 , Yuanyuan Cui  1 , Yaoxian Zhang  1 , Zhanli Liu  1 , Qiuli Zhang  1 , Wenyan Wu  1 , Zihao Zheng  1 , Shien Li  1 , Zhongjun Zhang  1 , Yali Li  1
Affiliations

A comprehensive study of immunology repertoires in both preoperative stage and postoperative stage in patients with colorectal cancer

Xicheng Liu et al. Mol Genet Genomic Med. 2019 Mar.

Abstract

Background: Colorectal cancer (CRC) is the 3rd most common cancer type in the world. The correlation between immune repertoire and prognosis of CRC has been well studied in the last decades. The diversity and stability of the immune cells can be measured by hypervariable complementarity-determining region 3 (CDR3) segments of the T-cell receptor (TCR).

Methods: In this study, we collected five healthy controls and 19 CRC patients' peripheral blood mononuclear cells (PBMCs) in three stages, namely 1 day preoperative, 3 days' postoperative, and 7 days' postoperative, respectively. Simultaneously, we have also done the comparative analysis of these two different anesthesia methods, namely TIVA and CEGA. Sequencing of the TCR segments has been performed by multiplex PCR and high-throughput next-generation sequencing. We also analyzed the distribution of CDR3 length, highly expansion clones (HECs), TRBV, and TRBJ gene usage.

Results: Our result showed a significant difference between TCR CDR3 length distribution and HEC distribution between CRC patients and healthy controls. We also found that TRBV11-2, TRBV12-1, TRBV16, TRBV3-2, TRBV4-2, TRBV4-3, TRBV5-4, TRBV6-8, TRBV7-8, TRBV7-9 and RBV11-2, TRBV12-1, TRBV16, TRBV3-2, TRBV4-2, TRBV4-3, TRBV5-4, TRBV6-8, TRBV7-8, and TRBV7-9 usages are different between CRC patients and healthy controls.

Conclusion: In conclusion, CRC patients were presented with different immune repertoire in comparison with healthy controls. In this study, significant difference in TRBV and TRBJ gene usage in between case and control group could provide some potential biomarker for the diagnosis and the treatment of the patients with CRC.

Keywords: CDR3; CEGA; CRC; TCRs; TIVA; repertoire.

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Conflict of interest statement

The authors have no conflict of interests to declare.

Figures

Figure 1
Figure 1
The details of data interpretation pipeline
Figure 2
Figure 2
Complementarity‐determining region 3 length distribution in healthy controls and preoperation colorectal cancer (CRC) patients. “Pink” bar represents the value of healthy controls’, and “green” bar represents the value of preoperative CRC patients’. Black triangle represents the significant different (p < 0.05)
Figure 3
Figure 3
R 2 comparison between the preoperation colorectal cancer (CRC) patients and healthy controls. H represents value of the healthy controls, and pre represents value of the preoperation CRC patients
Figure 4
Figure 4
(a) Comparison of highly expansion clone (HEC) number distribution between healthy controls’ and preoperative colorectal cancer (CRC) patients’. H represents HEC number of healthy controls, and pre represents HEC number of preoperation CRC patients. (b) Comparison of HEC number of CRC patients who takes TIVA. A1 represents the value of PMBCs collected at 1 day preoperation. A2 represents the value of PMBCs collected at 3 days’ postoperation. A3 represents the value of PMBCs collected at 7 days’ postoperation. (c) Comparison of HEC ratio of CRC patients who takes TIVA. A1 represents the value of PMBCs collected at 1 day preoperation. A2 represents the value of PMBCs collected at 3 days’ postoperation. A3 represents the value of PMBCs collected at 7 days’ postoperation. (d) Comparison of HEC ratio between TIVA and CEGA groups at different time points. A represents TIVA groups, and B represents CEGA. Time line 1 represents the value of PMBCs taken from 1 day preoperation, 3 days’ postoperation, and 7 days’ postoperation. (e) Comparison of HEC ratio between TIVA and CEGA groups at different time points. (A) represents TIVA groups, (B) represents CEGA. Time line 1 represents the value of PMBCs taken from 1 day preoperation, 3 days’ postoperation, and 7 days’ postoperation
Figure 5
Figure 5
(a) Comparison of highly expansion clone (HEC) number of colorectal cancer (CRC) patients who takes CEGA anesthesia. A1, represents the value of PMBCs collected at 1 day preoperation. A2 represents the value of PMBCs collected at 3 days’ postoperation. A3 represents the value of PMBCs collected at 7 days’ postoperation. (b) Comparison of HEC ratio of CRC patients who takes CEGA anesthesia. A1 represents the value of PMBCs collected at 1 day preoperation. A2 represents the value of PMBCs collected at 3 days’ postoperation. A3 represents the value of PMBCs collected at 7 days’ postoperation
Figure 6
Figure 6
(a) Percentage of top 60 used complementarity‐determining region 3 (CDR3) nucleotides. AC1, AD1, AE1, AF1, AH1, AJ1, BC1, BD1, BF1, BG1, BG1, BH1, and BI1 are all preoperation colorectal cancer (CRC) patients. HHT01, HHT02, HHT03, HHT04, and HHt05 are all healthy controls. (b) Percentage of top 60 used CDR3 amino acids. AC1, AD1, AE1, AF1, AH1, AJ1, BC1, BD1, BF1, BG1, BG1, BH1, and BI1 are all preoperation CRC patients. HHT01, HHT02, HHT03, HHT04, and HHt05 are all healthy controls
Figure 7
Figure 7
(a) Comparison of TRBV gene usage between preoperation patients and healthy controls. PH represents TRBV gene usage percentage of healthy controls, PRE, represents TRBV gene usage percentage of preoperation colorectal cancer (CRC) patients. Black triangle represents significant difference between healthy controls and preoperation CRC patients’ TRBV gene usage. (b) Comparison of TRBJ gene usage between preoperation patients and healthy controls. PH represents TRBV gene usage percentage of healthy controls, and PRE represents TRBV gene usage percentage of preoperation CRC patients. Black triangle represents significant difference between healthy controls and preoperation CRC patients’ TRBV gene usage
Figure 8
Figure 8
Heatmap of TOP 20 TRBV usage gene. A1 represents the value of PMBCs collected at 1 day preoperation. A2 represents the value of PMBCs collected at 3 days’ postoperation. A3 represents the value of PMBCs collected at 7 days’ postoperation
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