Colorectal cancer is the most common malignant tumor in human digestive tracts[26, 27]. With the development of researches in recent years, tumor markers have been used in the diagnosis of various tumors[28-31]. Tumor markers refer to substances synthesized and secreted by tumor cells and released into blood, cells and body fluids, which can reflect the occurrence and development of tumor[28, 31, 32]. CEA is a proteoglycan complex produced by colorectal cancer, which is widely found in cancers of the digestive system[33, 34]. CA24-2 is a kind of salivary acidified spingolipid glycosylated chain antigen, which is expressed in human pancreatic duct cells and colonic mucosal epithelial cells. It is mainly used in clinical detection of pancreatic cancer and colorectal cancer[35]. CA19-9 is a specific tumor marker for adenocarcinoma, but it lacks organ specificity and can be expressed in various malignancies such as pancreatic cancer, gastric cancer and colorectal cancer[36, 37]. The levels of CEA, CA19-9 and CA24-2 are significant for the diagnosis and prognosis monitoring of colorectal cancer.
In this study, three common serum markers (CEA, CA19-9 and CA24-2) of colorectal cancer were evaluated separately and jointly evaluated. The serum concentrations of CEA, CA24-2 and CA19-9 in colorectal cancer patients were significantly different from those in the control group, suggesting that CEA, CA24-2 and CA19-9 may be of important value in the diagnosis of colorectal cancer. By analyzing the relationship between serum CEA, CA19-9 and CA24-2 and clinical TNM staging, it was found that the concentrations of CEA, CA19-9 and CA24-2 changed with the degree of infiltration and TNM staging, showing a positive correlation. The concentration of CA24-2 was negatively correlated with the degree of tumor differentiation. The differences between CEA, CA19-9 concentration and tumor differentiation degree was not statistically significant. This is consistent with other studies[38, 39]. There are also inconsistencies with some studies[37, 40].
The sensitivity, specificity and ROC curve of these tumor markers were analyzed. The sensitivities of three individual markers were lower than 30%, which individual sensitivity of the tumor markers sorted in descending order was CEA> CA19-9> CA24-2. The specificities of three individual markers were more than 92%, and the specificity sorted in descending order was CA24-2> CA19-9> CEA. The sensitivities and specificities of tumor markers can be improved by combination of these markers. Although the combined detection of CEA, CA24-2 and CA19-9 can improve the ability to predict the risk of colorectal cancer, there were no significant differences compared with the single detection of CEA, CA24-2 and CA19-9.
There were no significant differences in age, gender, histology type, differentiation, depth of invasion and TNM staging between KRAS/NRAS (+) group and KRAS/NRAS (-) group, BRAF (+) group and BRAF (-) group, PIK3CA (+) group and PIK3CA (-) group, respectively. It showed that mutations in KRAS/NRAS, BRAF and PIK3CA genes were not associated with pathological status of colorectal cancer. There are different domestic and foreign studies on the relationship between KRAS/NRAS, BRAF and PIK3CA gene mutation status and pathological characteristics in colorectal cancer, which may be related to the detection method, sample size and regional differences[41-43].
In recent years, many new biomarkers of colorectal cancer have been found due to the research progress in molecular subtypes, DNA methylation, microRNA (miRNA) biogenesis and their role in colorectal cancer. These biomarkers can be used for diagnosis, individualized therapeutic effect and prognostic evaluation of colorectal cancer[44]. For example, hsa-mir-183-5p and hsa-mir-21-5p[45], hsa-mir-30a[46], hsa-mir-96[47], hsa-mir-21[48] for diagnosis of colorectal cancer. And hsa-mir-143 and hsa-mir-145 have promising prognostic value for colorectal cancer[49]. More and more studies have confirmed that the abnormal expression of miRNA in colorectal cancer tissues and plasma is closely related to diagnosis, treatment and prognosis. However, currently, miRNA as a tumor marker is still in the research stage, and there are still many problems to be solved. For example, the detection sample sizes of some experimental researches were small, and the selected miRNA tumor markers need further experimental verification. Sensitivity and specificity also need further confirmation. There is still no clear reference range for miRNA as a tumor marker. If peripheral blood miRNA is used as a tumor marker in clinic, reference range should be established and a standardized system should be established to ensure the accuracy and repeatability of miRNA detection. An increasing level of methylated DNA was association with advanced stage of colorectal cancer[50, 51]. But the specificity of methylation detection is low. The detection of tumor markers in peripheral blood has the advantages of less trauma, repeatability, and simultaneous detection of multiple indicators, which is an ideal method to determine tumor prognosis and follow-up. In gastrointestinal tumors, CEA, CA-199 and CA-242 are commonly used as tumor markers to monitor the occurrence, recurrence and disease changes of tumors. On the whole, we need to find more specific and sensitive markers for diagnosis, therapeutic evaluation and prognosis of colorectal cancer.