The Relevance Of Thymidine Kinase 1 In Patients With Colorectal Cancer

Objective(s):To compare the sensitivity and specificity of various serum tumor markers for the diagnosis of CRC and to evaluate the correlation between the clinicopathological features of colorectal cancer and the serological tumor markers expressed by them,and to investigate the factors influencing recurrence and metastasis after radical surgery in patients with colorectal cancer.Methods: This study retrospectively analyzed 79 patients with colorectal cancer who were hospitalized in the Second Department of General Surgery of the First People’s Hospital of Yunnan Province from January 2020 to October 2022.Another52 non-oncology patients who were hospitalized in our department during the same period were collected as a control group.Serological specimens were measured for each patient,and the expression levels of serum TK1,CA125,CA199,CA724,CEA,and AFP at 1m,3m,and 6m preoperatively and postoperatively,respectively.To compare the differences in serum TK1 concentrations between different ages,genders and TNM stages,to evaluate the correlation between the clinicopathological features of colorectal cancer and the serological tumor markers expressed by them,and to explore the role of different serological markers in the diagnosis of CRC.Results: In the present study,79 patients with colorectal cancer were enrolled.Among them,48 patients were male and 31 patients were female.Twenty-one patients were <50 years old,while 58 patients were ≥50 years old.65.56% of the patients had ulcerated tumor type,27.85% had augmented type,and only 7.59% had infiltrative type.Among the 79 patients with colorectal cancer,42 patients had colon cancer(16in ascending colon,5 in descending colon,and 21 in sigmoid colon)and 37 patients had rectal cancer,accounting for 53.16% and 46.84%,respectively.In addition,regarding the TNM staging showed that: the proportions of T1,T2,T3,and T4 were6.31%,16.46%,64.56,and 12.67%,respectively,and the proportions of N0,N1,and N2 were 48.10%,29.11%,and 22.79%,respectively(of which N2 a and N2 b were10.13% and 12.66%,respectively).In addition,we found that serum TK1 levels were significantly higher in patients with colorectal cancer(3.94 pmol/l vs.0.12 pmol/l),with a statistically significant difference between the two(P<0.001).The differences in serum TK1 levels were not statistically significant(P>0.05)between patients <50years old and ≥50 years old and between male and female patients.Meanwhile,we found that the blood TK1 level in stage I-II was 1.48±0.60 pmol/l,while in stage III-IV it was 4.34±1.19 pmol/l.The difference was statistically significant(P<0.05)compared to the blood TK1 level in stage III-IV.In addition,the levels of blood CEA,AFP,CA125,CA199,CA724 in stage I-II were not statistically significant(P>0.05)compared with those in stage III-IV.The preoperative serum TK1 concentrations in the hypofractionated group were significantly higher than those in the moderately and highly differentiated groups,and the differences were statistically significant(P<0.05);the preoperative serum TK1 levels in patients with distant metastases were much higher than those in patients without distant metastases.And the serum TK1 levels at all postoperative time points were smaller than those before surgery,and the differences were statistically significant(P<0.05).It is believed that the level of TK1 is related to the clinical stage and the degree of tumor differentiation,and the higher the clinical stage and the worse the differentiation,the higher the level of TK1 in patients.We routinely performed chemotherapy in 79 patients after surgery,and found that the serum TK1 level was 0.39±0.51 pmol/l 1 month after surgery in the surgery+chemotherapy group,which was much lower than the preoperative serum TK1 level,and the difference between them was statistically significant(P=0.035);similarly,the difference between serum TK1 3 months after surgery and 1 month after surgery was statistically significant(P=0.024);there was also a statistically significant difference in serum TK1 levels at 6 months postoperatively compared to serum TK1 levels at 3 months postoperatively(P=0.044).We also analyzed serum TK1 levels at each postoperative time point in the surgery+chemotherapy+targeted therapy group and found that serum TK1 levels at 1 month postoperatively were 1.64±0.96 pmol/l,which were much lower than preoperative serum TK1 levels,and the difference between the two was statistically significant(P=0.038);while serum TK1 levels at 3months postoperatively compared with 1 month postoperatively were statistically significant(P=0.049);and the difference between serum TK1 levels at 6 months postoperatively compared with serum TK1 levels at 3 months postoperatively of0.86±0.86 pmol/l was not statistically significant(P=0.689).We concluded that the sensitivity of serum TK1 is different in different treatment modalities.To compare the sensitivity of TK1 with other tumor markers in preoperative and postoperative diagnosis of colorectal cancer,we plotted the ROC curve and found that the AUC area of serum TK1 was higher than that of serum CEA,AFP,CA125,CA199 and CA724 before surgery,indicating that the sensitivity of TK1 in preoperative diagnosis of colorectal cancer was higher,while the postoperative 1 month,3 months and 6 months area under the ROC curve,we can see that the area of serum TK1 is lower than that of serum CEA,but still higher than that of CA125,CA199,CA724 and AFP,for which we believe that serum TK1 has potential value in the diagnosis of colorectal cancer prognosis.Conclusion(s): In this study,we found that serum TK1 levels were significantly lower in healthy people than in colorectal cancer patients,which can be used as an indicator for preoperative screening of colorectal cancer.And the level of TK1 was related to clinical stage and tumor differentiation,and the higher the clinical stage,the higher the level of TK1 in patients with poorer differentiation.In terms of treatment,we found that the level of serum TK1 was gradually decreasing through different treatment modalities,especially in the early treatment stage,indicating that the sensitivity of serum TK1 to different treatment modalities was different.In addition,by comparing serum TK1 with CA125,CA199,CA724,CEA and other conventional serological tumor markers in colorectal cancer diagnosis and prognosis by ROC,we believe that serum TK1 can be used as one of the adjuvant indicators for colorectal cancer diagnosis in clinical practice.In conclusion,serum TK1 may be a potential indicator for the diagnosis of colorectal cancer as well as for the assessment of the prognosis of colorectal cancer.