A predictive model for the risk of lymph node metastasis in colorectal cancer_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

LIU Zitao ¹ , HUANG Chao ¹ , TIAN Huakai ¹ , ZHOU Taicheng ² , XIA Yongqiang ¹ , XIAO Li ¹ ,  ZONG Zhen ¹

1. Department of Gastrointestinal Surgery, The Second Affiliated Hospital of Nanchang University, Nanchang 330006, P. R. China;
2. Department of Gastrointestinal, Hernia and Abdominal Surgery, The Sixth Hospital of Sun Yat-Sen University, Guangzhou 510655, P. R. China;

Corresponding?author：

ZONG Zhen, Email: zongzhenmd@126.com

Keywords：

colorectal cancer; lymph node metastasis; risk factor; predictive model

DOI：

10.7507/1007-9424.202011102

Video：

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Objective To explore the risk factors of lymph node metastasis in patients with colorectal cancer, and construct a risk prediction model to provide reference for clinical diagnosis and treatment.Methods The clinicopathological data of 416 patients with colorectal cancer who underwent radical resection of colorectal cancer in the Department of Gastrointestinal Surgery of the Second Affiliated Hospital of Nanchang University from May 2018 to December 2019 were retrospectively analyzed. The correlation between lymph node metastasis and preoperative inflammatory markers, clinicopathological factors and tumor markers were analyzed. Logistic regression was used to analyze the risk factors of lymph node metastasis, and R language was used to construct nomogram model for evaluating the risk of colorectal cancer lymph node metastasis before surgery, and drew a calibration curve and compared with actual observations. The Bootstrap method was used for internal verification, and the consistency index (C-index) was calculated to evaluate the accuracy of the model.Results The results of univariate analysis showed that factors such as sex, age, tumor location, smoking history, hypertension and diabetes history were not significantly related to lymph node metastasis (all P>0.05). The factors related to lymph node metastasis were tumor size, T staging, tumor differentiation level, fibrinogen, neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR), fibrinogen/albumin ratio (FAR), fibrinogen/prealbumin ratio (FpAR), CEA, and CA199 (all P<0.05). The results of logistic regression analysis showed the FpAR [OR=3.630, 95%CI (2.208, 5.968), P<0.001], CA199 [OR=2.058, 95%CI (1.221, 3.470), P=0.007], CEA [OR=2.335, 95%CI (1.372, 3.975), P=0.002], NLR [OR=2.532, 95%CI (1.491, 4.301), P=0.001], and T staging were independent risk factors for lymph node metastasis. The above independent risk factors were enrolled to construct regression equation and nomogram model, the area under the ROC curve of this equation was 0.803, and the sensitivity and specificity were 75.2% and 73.5%, respectively. The consistency index (C-index) of the nomogram prediction model in this study was 0.803, and the calibration curve showed that the result of predicting lymph node metastasis was highly consistent with actual observations.Conclusions FpAR>0.018, NLR>3.631, CEA>4.620 U/mL, CA199>21.720 U/mL and T staging are independent risk factors for lymph node metastasis. The nomogram can accurately predict the risk of lymph node metastasis in patients with colorectal cancer before surgery, and provide certain assistance in the formulation of clinical diagnosis and treatment plans.

Citation： LIU Zitao, HUANG Chao, TIAN Huakai, ZHOU Taicheng, XIA Yongqiang, XIAO Li, ZONG Zhen. A predictive model for the risk of lymph node metastasis in colorectal cancer. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2021, 28(8): 1045-1050. doi: 10.7507/1007-9424.202011102 Copy

1.	王寧, 劉碩, 楊雷, 等. 2018 全球癌癥統計報告解讀. 腫瘤綜合治療電子雜志, 2019, 5(1): 87-97.
2.	朱渝軍, 陳剛, 胡佳, 等. 腹腔鏡與開腹手術治療結直腸癌的臨床療效及術后并發癥的比較. 實用癌癥雜志, 2016, 31(1): 103-106.
3.	劉啟志, 郝立強, 樓征, 等. 結直腸癌術后早期和晚期復發轉移與臨床病理特征的關系. 中華普通外科雜志, 2019, 34(8): 675-678.
4.	胡俊. MRI在直腸癌術前精準分期及精準定位評估中的應用. 吉林大學, 2019.
5.	路成文, 張彬. CT、MR 對盆腔結、直腸癌術前 TN 分期的應用價值. 醫學影像學雜志, 2015, 25(7): 1204-1208, 1220.
6.	覃羅, 姚暉, 徐亮. 中性粒細胞與淋巴細胞比值聯合檢測纖維蛋白原對結直腸癌預后的判斷價值. 中國免疫學雜志, 2017, 33(4): 527-532.
7.	Li X, Guo D, Chu L, et al. Potential diagnostic value of combining inflammatory cell ratios with carcinoembryonic antigen for colorectal cancer. Cancer Manag Res, 2019, 11: 9631-9640.
8.	汪曉東, 劉丹, 呂東昊, 等. 術前纖維蛋白原水平與結直腸癌病理分期的關系. 中華實用診斷與治療雜志, 2009, 23(7): 643-645.
9.	廖存, 馬輝, 阮國添, 等. 435 例結直腸癌患者術前血清前白蛋白水平與腫瘤的臨床病理特征的關系研究. 結直腸肛門外科, 2019, 25(3): 284-288, 293.
10.	孫帆. 纖維蛋白原與前白蛋白比值在結直腸癌診斷及預后中的應用價值. 南昌大學, 2018.
11.	姚宏偉, 吳鴻偉, 劉蔭華. 美國癌癥聯合委員會第八版結直腸癌分期更新及其“預后和預測”評價體系. 中華胃腸外科雜志, 2017, 20(1): 24-27.
12.	Ullman TA, Itzkowitz SH. Intestinal inflammation and cancer. Gastroenterology, 2011, 140(6): 1807-1816.
13.	季暢, 李艷華. 慢性炎癥細胞因子表達與結直腸癌相關性分析. 中國實驗診斷學, 2020, 24(4): 626-627.
14.	丁一波, 陳一凡, 曹廣文. 癌癥進化發育學的新證據: 結直腸癌和肝細胞癌的研究發現. 中國癌癥防治雜志, 2020, 12(1): 1-5.
15.	Li MX, Liu XM, Zhang XF, et al. Prognostic role of neutrophil-to-lymphocyte ratio in colorectal cancer: a systematic review and meta-analysis. Int J Cancer, 2014, 134(10): 2403-2413.
16.	Fül?p ZZ, Gurzu S, Fül?p RL, et al. Prognostic impact of the neutrophil-to-lymphocyte and lymphocyte-to-monocyte ratio, in patients with rectal cancer: A retrospective study of 1 052 patients. J Pers Med, 2020, 10(4): 173.
17.	彭維忠, 楊浩潔, 張克蘭, 等. 外周血 NLR 或 PLR 與結直腸癌預后的相關性研究進展. 中國免疫學雜志, 2017, 33(12): 1902-1906.
18.	Peng HX, Yang L, He BS, et al. Combination of preoperative NLR, PLR and CEA could increase the diagnostic efficacy for Ⅰ-Ⅲ stage CRC. J Clin Lab Anal, 2017, 31(5): e22075.
19.	Falanga A, Marchetti M, Vignoli A. Coagulation and cancer: biological and clinical aspects. J Thromb Haemost, 2013, 11(2): 223-233.
20.	王勝強. 凝血五項在結直腸惡性腫瘤血行轉移中的變化及意義. 中國醫科大學, 2018.
21.	辛衡, 周建平, 高威, 等. 結直腸癌患者術前血漿纖維蛋白原、癌胚抗原、糖類抗原 19-9 水平與臨床病理特征的關系. 中國醫科大學學報, 2020, 49(11): 1007-1010.
22.	Zheng S, Shen J, Jiao Y, et al. Platelets and fibrinogen facilitate each other in protecting tumor cells from natural killer cytotoxicity. Cancer Sci, 2009, 100(5): 859-865.
23.	Kawai K, Kitayama J, Tsuno NH, et al. Hyperfibrinogenemia after preoperative chemoradiotherapy predicts poor response and poor prognosis in rectal cancer. Int J Colorectal Dis, 2011, 26(1): 45-51.
24.	Wu M, Pan Y, Jia Z, et al. Preoperative plasma fibrinogen and serum albumin score is an independent prognostic factor for resectable stage Ⅱ-Ⅲ gastric cancer. Dis Markers, 2019, 2019: 9060845.
25.	Fujii T, Sutoh T, Morita H, et al. Serum albumin is superior to prealbumin for predicting short-term recurrence in patients with operable colorectal cancer. Nutr Cancer, 2012, 64(8): 1169-1173.
26.	Hu WH, Cajas-Monson LC, Eisenstein S, et al. Preoperative malnutrition assessments as predictors of postoperative mortality and morbidity in colorectal cancer: an analysis of ACS-NSQIP. Nutr J, 2015, 14: 91.
27.	Sun F, Tan YA, Gao QF, et al. Circulating fibrinogen to pre-albumin ratio is a promising biomarker for diagnosis of colorectal cancer. J Clin Lab Anal, 2019, 33(1): e22635.
28.	Gao Y, Wang J, Zhou Y, et al. Evaluation of serum CEA, CA19-9, CA72-4, CA125 and ferritin as diagnostic markers and factors of clinical parameters for colorectal cancer. Sci Rep, 2018, 8(1): 2732.
29.	McKeown E, Nelson DW, Johnson EK, et al. Current approaches and challenges for monitoring treatment response in colon and rectal cancer. J Cancer, 2014, 5(1): 31-43.
30.	Tsai HL, Cheng KI, Lu CY, et al. Prognostic significance of depth of invasion, vascular invasion and numbers of lymph node retrievals in combination for patients with stage Ⅱcolorectal cancer undergoing radical resection. J Surg Oncol, 2008, 97(5): 383-387.
31.	彭詡淋, 向征. 2 型糖尿病與結直腸癌淋巴結轉移關系的病例對照研究. 中國臨床研究, 2020, 33(1): 41-44.
32.	包向東, 程恒金, 周慧潔, 等. 結直腸癌淋巴結轉移多因素回歸分析. 實用醫學雜志, 2012, 28(6): 965-967.

1. 王寧, 劉碩, 楊雷, 等. 2018 全球癌癥統計報告解讀. 腫瘤綜合治療電子雜志, 2019, 5(1): 87-97.
2. 朱渝軍, 陳剛, 胡佳, 等. 腹腔鏡與開腹手術治療結直腸癌的臨床療效及術后并發癥的比較. 實用癌癥雜志, 2016, 31(1): 103-106.
3. 劉啟志, 郝立強, 樓征, 等. 結直腸癌術后早期和晚期復發轉移與臨床病理特征的關系. 中華普通外科雜志, 2019, 34(8): 675-678.
4. 胡俊. MRI在直腸癌術前精準分期及精準定位評估中的應用. 吉林大學, 2019.
5. 路成文, 張彬. CT、MR 對盆腔結、直腸癌術前 TN 分期的應用價值. 醫學影像學雜志, 2015, 25(7): 1204-1208, 1220.
6. 覃羅, 姚暉, 徐亮. 中性粒細胞與淋巴細胞比值聯合檢測纖維蛋白原對結直腸癌預后的判斷價值. 中國免疫學雜志, 2017, 33(4): 527-532.
7. Li X, Guo D, Chu L, et al. Potential diagnostic value of combining inflammatory cell ratios with carcinoembryonic antigen for colorectal cancer. Cancer Manag Res, 2019, 11: 9631-9640.
8. 汪曉東, 劉丹, 呂東昊, 等. 術前纖維蛋白原水平與結直腸癌病理分期的關系. 中華實用診斷與治療雜志, 2009, 23(7): 643-645.
9. 廖存, 馬輝, 阮國添, 等. 435 例結直腸癌患者術前血清前白蛋白水平與腫瘤的臨床病理特征的關系研究. 結直腸肛門外科, 2019, 25(3): 284-288, 293.
10. 孫帆. 纖維蛋白原與前白蛋白比值在結直腸癌診斷及預后中的應用價值. 南昌大學, 2018.
11. 姚宏偉, 吳鴻偉, 劉蔭華. 美國癌癥聯合委員會第八版結直腸癌分期更新及其“預后和預測”評價體系. 中華胃腸外科雜志, 2017, 20(1): 24-27.
12. Ullman TA, Itzkowitz SH. Intestinal inflammation and cancer. Gastroenterology, 2011, 140(6): 1807-1816.
13. 季暢, 李艷華. 慢性炎癥細胞因子表達與結直腸癌相關性分析. 中國實驗診斷學, 2020, 24(4): 626-627.
14. 丁一波, 陳一凡, 曹廣文. 癌癥進化發育學的新證據: 結直腸癌和肝細胞癌的研究發現. 中國癌癥防治雜志, 2020, 12(1): 1-5.
15. Li MX, Liu XM, Zhang XF, et al. Prognostic role of neutrophil-to-lymphocyte ratio in colorectal cancer: a systematic review and meta-analysis. Int J Cancer, 2014, 134(10): 2403-2413.
16. Fül?p ZZ, Gurzu S, Fül?p RL, et al. Prognostic impact of the neutrophil-to-lymphocyte and lymphocyte-to-monocyte ratio, in patients with rectal cancer: A retrospective study of 1 052 patients. J Pers Med, 2020, 10(4): 173.
17. 彭維忠, 楊浩潔, 張克蘭, 等. 外周血 NLR 或 PLR 與結直腸癌預后的相關性研究進展. 中國免疫學雜志, 2017, 33(12): 1902-1906.
18. Peng HX, Yang L, He BS, et al. Combination of preoperative NLR, PLR and CEA could increase the diagnostic efficacy for Ⅰ-Ⅲ stage CRC. J Clin Lab Anal, 2017, 31(5): e22075.
19. Falanga A, Marchetti M, Vignoli A. Coagulation and cancer: biological and clinical aspects. J Thromb Haemost, 2013, 11(2): 223-233.
20. 王勝強. 凝血五項在結直腸惡性腫瘤血行轉移中的變化及意義. 中國醫科大學, 2018.
21. 辛衡, 周建平, 高威, 等. 結直腸癌患者術前血漿纖維蛋白原、癌胚抗原、糖類抗原 19-9 水平與臨床病理特征的關系. 中國醫科大學學報, 2020, 49(11): 1007-1010.
22. Zheng S, Shen J, Jiao Y, et al. Platelets and fibrinogen facilitate each other in protecting tumor cells from natural killer cytotoxicity. Cancer Sci, 2009, 100(5): 859-865.
23. Kawai K, Kitayama J, Tsuno NH, et al. Hyperfibrinogenemia after preoperative chemoradiotherapy predicts poor response and poor prognosis in rectal cancer. Int J Colorectal Dis, 2011, 26(1): 45-51.
24. Wu M, Pan Y, Jia Z, et al. Preoperative plasma fibrinogen and serum albumin score is an independent prognostic factor for resectable stage Ⅱ-Ⅲ gastric cancer. Dis Markers, 2019, 2019: 9060845.
25. Fujii T, Sutoh T, Morita H, et al. Serum albumin is superior to prealbumin for predicting short-term recurrence in patients with operable colorectal cancer. Nutr Cancer, 2012, 64(8): 1169-1173.
26. Hu WH, Cajas-Monson LC, Eisenstein S, et al. Preoperative malnutrition assessments as predictors of postoperative mortality and morbidity in colorectal cancer: an analysis of ACS-NSQIP. Nutr J, 2015, 14: 91.
27. Sun F, Tan YA, Gao QF, et al. Circulating fibrinogen to pre-albumin ratio is a promising biomarker for diagnosis of colorectal cancer. J Clin Lab Anal, 2019, 33(1): e22635.
28. Gao Y, Wang J, Zhou Y, et al. Evaluation of serum CEA, CA19-9, CA72-4, CA125 and ferritin as diagnostic markers and factors of clinical parameters for colorectal cancer. Sci Rep, 2018, 8(1): 2732.
29. McKeown E, Nelson DW, Johnson EK, et al. Current approaches and challenges for monitoring treatment response in colon and rectal cancer. J Cancer, 2014, 5(1): 31-43.
30. Tsai HL, Cheng KI, Lu CY, et al. Prognostic significance of depth of invasion, vascular invasion and numbers of lymph node retrievals in combination for patients with stage Ⅱcolorectal cancer undergoing radical resection. J Surg Oncol, 2008, 97(5): 383-387.
31. 彭詡淋, 向征. 2 型糖尿病與結直腸癌淋巴結轉移關系的病例對照研究. 中國臨床研究, 2020, 33(1): 41-44.
32. 包向東, 程恒金, 周慧潔, 等. 結直腸癌淋巴結轉移多因素回歸分析. 實用醫學雜志, 2012, 28(6): 965-967.

CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

A predictive model for the risk of lymph node metastasis in colorectal cancer

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