Expression of BLM helicase and TIDC in colon cancer tissues and their relationship withpostoperative prognosis of patients_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

NI Zhihai ,  XUE Zhiyou

Department of Anorectal Surgery, Xinhua Hospital Affiliated to Dalian University, Dalian, Liaoning 116021, P. R. China;

Corresponding author：

XUE Zhiyou, Email: xuezy0506@126.com

Keywords：

colon cancer; Bloom syndrome helicase; tumor infiltrating dendritic cell; prognostic marker

DOI：

10.7507/1007-9424.202110113

Video：

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Objective To investigate the expression of Bloom syndrome (BLM) helicase and tumor infiltrating dendritic cells (TIDC) in colon cancer tissues and their relationship with the prognosis of patients after surgery. Methods Onehundred and sixty-eight patients with colon cancer who underwent surgical resection in our hospital from June 2014 to August 2016 were selected as the research objects. The specimens of surgically resected colon cancer tissues and adjacent tissues archived by the pathology department were obtained, and the expression of BLM helicase and TIDC density were detected by immunohistochemistry. Pearson was used to analyze the correlation between BLM helicase expression and TIDC density, and the relationship between the expression of BLM helicase and TIDC density and the clinicopathological features of colon cancer was analyzed by using χ² test or Wilcoxon rank test. The influencing factors of postoperative survival of patients with colon cancer were analyzed by Cox proportional hazards regression model. Results The relative expression of BLM helicase in colon cancer tissues was higher than that in adjacent tissues (1.49±0.33 vs. 1.02±0.17), while the TIDC density was lower than that in adjacent tissues [(9.53±2.36)% vs. (12.36±2.37)%], the differences were statistically significant (P<0.05). Pearson correlation analysis showed that there was a negative correlation between the expression of BLM helicase and TIDC density (r=–0.588, P<0.05). The expression of BLM helicase and TIDC density were correlated with tumor differentiation, clinical stage and lymph node metastasis (P<0.05). That is, those with high expression of BLM helicase and low density of TIDC had low degree of tumor differentiation, late clinical grade, and higher ratio of lymph node metastasis. Sixty-three cases died (37.5%) during the follow-up period (16–60 months, medium follow up 45 months). Log-rank analysis showed that the 5-year cumulative survival rate of the BLM helicase-low expression group was higher than that of the high expression group, and that of the TIDC-low density group was lower than that of the high density group (P<0.05). Cox regression analysis showed that the high expression of BLM helicase, low density of TIDC, low degree of tumor differentiation, late stage and lymph node metastasis were risk factors affecting the postoperative survival of patients with colon cancer (P<0.05). Conclusion The abnormal expression of BLM helicase and TIDC density in colon cancer tissues are related to the degree of differentiation and lymph node metastasis, which are risk factors affecting the long-term survival of patients with colon cancer.

Citation： NI Zhihai, XUE Zhiyou. Expression of BLM helicase and TIDC in colon cancer tissues and their relationship withpostoperative prognosis of patients. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2022, 29(8): 1061-1066. doi: 10.7507/1007-9424.202110113 Copy

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2.	Chen H, Luo J, Guo J. Development and validation of a five-immune gene prognostic risk model in colon cancer. BMC Cancer, 2020, 20(1): 395. doi: 10.1186/s12885-020-06799-0.
3.	Lao VV, Welcsh P, Luo Y, et al. Altered RECQ helicase expression in sporadic primary colorectal cancers. Transl Oncol, 2013, 6(4): 458-469.
4.	Bowden AR, Tischkowitz M. Clinical implications of germline mutations in breast cancer genes: RECQL. Breast Cancer Res Treat, 2019, 174(3): 553-560.
5.	Nishimura J, Tanaka H, Yamakoshi Y, et al. Impact of tumor-infiltrating LAMP-3 dendritic cells on the prognosis of esophageal squamous cell carcinoma. Esophagus, 2019, 16(4): 333-344.
6.	胡永挑, 曾小康. 直肠癌组织中肿瘤浸润性树突状细胞数量和表型的改变及临床意义. 中国普通外科杂志, 2019, 28(6): 768-772.
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9.	中国医师协会外科医师分会, 中华医学会外科分会胃肠外科学组, 中华医学会外科分会结直肠外科学组, 等. 中国结直肠癌肝转移诊断和综合治疗指南(V2020). 中华胃肠外科杂志, 2021, 24(1): 1-13.
10.	Sun C, Mezzadra R, Schumacher TN. Regulation and function of the PD-L1 checkpoint. Immunity, 2018, 48(3): 434-452.
11.	Melaiu O, Chierici M, Lucarini V, et al. Cellular and gene signatures of tumor-infiltrating dendritic cells and natural-killer cells predict prognosis of neuroblastoma. Nat Commun, 2020, 11(1): 5992. doi: 10.1038/s41467-020-19781-y.
12.	Bononi A, Goto K, Ak G, et al. Heterozygous germline BLM mutations increase susceptibility to asbestos and mesothelioma. Proc Natl Acad Sci U S A, 2020, 117(52): 33466-33473.
13.	Ledet EM, Antonarakis ES, Isaacs WB, et al. Germline BLM mutations and metastatic prostate cancer. Prostate, 2020, 80(2): 235-237.
14.	Shuai F, Wang B, Dong S. miR-522-3p promotes tumorigenesis in human colorectal cancer via targeting bloom syndrome protein. Oncol Res, 2018, 26(7): 1113-1121.
15.	Wang CX, Zhang ZL, Yin QK. Design, synthesis, and evaluation of new quinazolinone derivatives that inhibit bloom syndrome protein (BLM) hHelicase, trigger DNA damage at the telomere region, and synergize with PARP inhibitors. J Med Chem, 2020, 63(17): 9752-9772.
16.	闫巧辉, 邢国臣, 潘琼. 恶性肿瘤特异生长因子和肿瘤浸润性树突状细胞在子宫内膜癌患者中的表达及临床意义. 现代肿瘤医学, 2019, 27(5): 845-848.
17.	Kießler M, Plesca I, Sommer U, et al. Tumor-infiltrating plasmacytoid dendritic cells are associated with survival in human colon cancer. J Immunother Cancer, 2021, 9(3): e001813. doi: 10.1136/jitc-2020-001813.
18.	张杨蕊. DEAD-box解螺旋酶46基因沉默对乳腺癌细胞增殖和凋亡的影响. 安徽医药, 2020, 24(12): 2489-2493, 后插5.
19.	秦琼, 杨林, 周爱萍, 等. 癌结节对Ⅲ期结肠癌患者预后的影响及将癌结节数目纳入淋巴结计数整体评估TNM分期的探索性研究. 中华胃肠外科杂志, 2019, 22(12): 1152-1158.
20.	Balança CC, Salvioni A, Scarlata CM, et al. PD-1 blockade restores helper activity of tumor-infiltrating, exhausted PD-1^hiCD39⁺CD4 T cells. JCI Insight, 2021, 6(2): e142513. doi: 10.1172/jci.insight.142513.

1. 郭天安, 谢丽, 赵江, 等. 中国结直肠癌1988-2009年发病率和死亡率趋势分析. 中华胃肠外科杂志, 2018, 21(1): 33-40.
2. Chen H, Luo J, Guo J. Development and validation of a five-immune gene prognostic risk model in colon cancer. BMC Cancer, 2020, 20(1): 395. doi: 10.1186/s12885-020-06799-0.
3. Lao VV, Welcsh P, Luo Y, et al. Altered RECQ helicase expression in sporadic primary colorectal cancers. Transl Oncol, 2013, 6(4): 458-469.
4. Bowden AR, Tischkowitz M. Clinical implications of germline mutations in breast cancer genes: RECQL. Breast Cancer Res Treat, 2019, 174(3): 553-560.
5. Nishimura J, Tanaka H, Yamakoshi Y, et al. Impact of tumor-infiltrating LAMP-3 dendritic cells on the prognosis of esophageal squamous cell carcinoma. Esophagus, 2019, 16(4): 333-344.
6. 胡永挑, 曾小康. 直肠癌组织中肿瘤浸润性树突状细胞数量和表型的改变及临床意义. 中国普通外科杂志, 2019, 28(6): 768-772.
7. 中华人民共和国卫生和计划生育委员会医政医管局, 中华医学会肿瘤学分会. 中国结直肠癌诊疗规范(2017年版). 中华外科杂志, 2018, 56(4): 241-258.
8. 王妹兴, 印季良, 肖谜, 等. 结肠癌组织中miR-340和CCND1表达及临床意义. 临床肿瘤学杂志, 2019, 24(6): 538-542.
9. 中国医师协会外科医师分会, 中华医学会外科分会胃肠外科学组, 中华医学会外科分会结直肠外科学组, 等. 中国结直肠癌肝转移诊断和综合治疗指南(V2020). 中华胃肠外科杂志, 2021, 24(1): 1-13.
10. Sun C, Mezzadra R, Schumacher TN. Regulation and function of the PD-L1 checkpoint. Immunity, 2018, 48(3): 434-452.
11. Melaiu O, Chierici M, Lucarini V, et al. Cellular and gene signatures of tumor-infiltrating dendritic cells and natural-killer cells predict prognosis of neuroblastoma. Nat Commun, 2020, 11(1): 5992. doi: 10.1038/s41467-020-19781-y.
12. Bononi A, Goto K, Ak G, et al. Heterozygous germline BLM mutations increase susceptibility to asbestos and mesothelioma. Proc Natl Acad Sci U S A, 2020, 117(52): 33466-33473.
13. Ledet EM, Antonarakis ES, Isaacs WB, et al. Germline BLM mutations and metastatic prostate cancer. Prostate, 2020, 80(2): 235-237.
14. Shuai F, Wang B, Dong S. miR-522-3p promotes tumorigenesis in human colorectal cancer via targeting bloom syndrome protein. Oncol Res, 2018, 26(7): 1113-1121.
15. Wang CX, Zhang ZL, Yin QK. Design, synthesis, and evaluation of new quinazolinone derivatives that inhibit bloom syndrome protein (BLM) hHelicase, trigger DNA damage at the telomere region, and synergize with PARP inhibitors. J Med Chem, 2020, 63(17): 9752-9772.
16. 闫巧辉, 邢国臣, 潘琼. 恶性肿瘤特异生长因子和肿瘤浸润性树突状细胞在子宫内膜癌患者中的表达及临床意义. 现代肿瘤医学, 2019, 27(5): 845-848.
17. Kießler M, Plesca I, Sommer U, et al. Tumor-infiltrating plasmacytoid dendritic cells are associated with survival in human colon cancer. J Immunother Cancer, 2021, 9(3): e001813. doi: 10.1136/jitc-2020-001813.
18. 张杨蕊. DEAD-box解螺旋酶46基因沉默对乳腺癌细胞增殖和凋亡的影响. 安徽医药, 2020, 24(12): 2489-2493, 后插5.
19. 秦琼, 杨林, 周爱萍, 等. 癌结节对Ⅲ期结肠癌患者预后的影响及将癌结节数目纳入淋巴结计数整体评估TNM分期的探索性研究. 中华胃肠外科杂志, 2019, 22(12): 1152-1158.
20. Balança CC, Salvioni A, Scarlata CM, et al. PD-1 blockade restores helper activity of tumor-infiltrating, exhausted PD-1^hiCD39⁺CD4 T cells. JCI Insight, 2021, 6(2): e142513. doi: 10.1172/jci.insight.142513.

CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Expression of BLM helicase and TIDC in colon cancer tissues and their relationship withpostoperative prognosis of patients

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