Clinical Study Of CA125 As A Prognostic Indicator Of Normal Preoperative CEA In Colon Cancer Patients

Obective:Colon cancer(CC)is a common malignant tumor of the digestive tract.CEA is a commonly used tumor marker for digestive tract tumors.At present,CEA has certain reference value for its recurrence and metastasis in clinical colon cancer patients.However,there are still relatively few studies on tumor markers related to the prognosis of OS and DFS in patients with normal CEA before surgery.This study aims to explore the feasibility of judging the prognosis of colon cancer patients with normal preoperative serum CEA levels,and provide clinical reference value for the prognosis of patients undergoing radical resection.This study shows for the first time the predictive value of preoperative serum CA125 levels for the prognostic value of CC patients with normal CEA levels.Methods:Regression analysis of colon cancer patients admitted to the Third Affiliated Hospital of Kunming Medical University from January 2013 to December2017 who underwent radical surgery was performed.The clinical medical records included preoperative and postoperative datasuch as CEA,CA125,CA199,CA242 and CA724 levels,clinical data,pathological datawere collected.Follow-up data were collected from Yunnan Cancer Center.The deadline for follow-up is December 2020.The patient’s death was taken as the end-point event for overall survival,and tumor recurrence was taken as the end-point event for disease-free survival to determine the prognosis of patients after radical resection.The correlation between serum tumor markers level and clinical and pathological factors were analyzed.The correlation between OS and DFS was analyzed by using survival function and correlation rank sum test,including gender,age,history,tumor size,BMI,KPS score,tumor differentiation,histological type,TNM stage,etc.In this study,through single factor analysis and multivariate Cox regression analysis,possible risk factors were screened out into the model,and risk factors that had little or no correlation with CC were removed,ensuring the reliability and accuracy of the selected CC prognostic indicators.In addition,the indicators were included in the Cox regression model for analysis and the nomogram was established.All data were statistically analyzed using R studio 2.3.Part of the work of data collection and analysis usedPython 3.7.Results:(1)A total of 1031 patients with colon cancer admitted to Yunnan Cancer Hospital(the Third Affiliated Hospital of Kunming Medical University)from January 2013 to December 2017 were selected.After the inclusion and exclusion criteria of this study,a total of 440 patients with CEA<5μg/L were regarded as the study objects.Among the gastrointestinal tumor markers CA125,CA199,CA242 and CA724,CA125 was selected by the random forest algorithm to be an important indicator of prognosis for patients with a normal CEA level,which was verified by Logistic regression(P<0.001).(2)The results of multivariate Cox regression analysis suggest that CA125≥35kU/L,N staging and histological type are independent risk factors for CC witha normal CEA level.Based on these risk factors,construct a CC-assisted diagnosis and prediction model,and further achieve visualization by drawing a nomogram.(3)CA125 has a higher specificity of 0.65 in OS,but a lower sensitivity of 0.63;the combined use of CA125+N staging+histological type can improve the accuracy more than using the risk model alone(AUC=0.783,95% CI=0.708-0.845,P<0.001),specificity 0.81 and sensitivity 0.72.Using Harrell’s C-index to sample 500 times through Bootstrap,the discrimination C-index is 0.771(95% Cl0.711-0.830,P<0.001).The results show that the model has a certain degree of discrimination.(4)The same CA125+N staging+histological type combined use can improve the accuracy in DFS more than using the risk model alone(AUC=0.769,95%CI=0.704-0.828,P<0.001),specificity 0.80 And the sensitivity is 0.72.Using Harrell’s C-index to sample 500 times through Bootstrap,the discrimination C-index is 0.783(95% CI 0.721-0.845,P<0.001).Conclusions:(1)This study is the first time to demonstrate the predictive value of preoperative serum CA125 level in colon cancer patients with normal CEA level.Preoperative serum CA125 can be used as a tumor marker for independent prognostic risk factors in colon cancer patients with normal CEA levels.(2)Using machine learning random forest algorithm,CA125 was identified as an important prognostic variable with death and recurrence as outcomes.Kaplan Meier analysis showed that the prognosis of patients with CA125≥ 35ku/L was significantly worse than that of patients with CA125 <35ku/L in OS analysis.Postoperative monitoring should be strengthened to detect postoperative recurrence in time,and appropriate treatment should be selected to improve the prognosis of patients.Serum CA125 can be used as an important index to predict recurrence and assist TNM staging to judge prognosis in patients with stage Ⅰ-Ⅲ colon cancer.(3)Histological type and lymph node metastasis are independent prognostic risk factors for colon cancer patients with normal CEA levels.(4)Through retrospective analysis,this study found that in patients with normal preoperative CEA,lymph node metastasis,histological type and elevated CA125 were risk factors for prognosis and recurrence after radical resection of stage Ⅰ-Ⅲ colon cancer.