CRC is one of the leading causes of cancer-related death worldwide. More than 80% of the CRC patients were over 60 years old when they were diagnosed with colorectal cancer, and over 20% of the patients had distant metastasis with a five-year survival rate of less than 15%3,24. Early screening of colorectal cancer is very important for the treatment and survival rate of patients. Fecal immunochemical test (FIT), sigmoidoscopy, and colonoscopy (offered if FIT or sigmoidoscopy positive) are recommended for CRC screening in asymptomatic subjects 50 years or older4,25. Although there is not sufficient evidence to suggest the analysis of biomarkers such as DNA, RNA, or protein in the blood, with the rapid development of molecular biological technology tools, the improvement of sensitivity, and the reduction of cost, these tools will be gradually applied to clinical practice, and will probably be developed on a large scale26. In recent decades, more and more studies are looking for ideal blood biomarkers for CRC with the characteristics of easy quantification, high specificity and sensitivity, reliability, and good repeatability. Previous studies have shown that circulating cell-free DNA27–29, microRNAs (e.g., miR-21, miR-24)30–32, long noncoding RNAs (e.g., HIF1A-AS1, CCAT1, HOTAIR)33,34 and protein (e.g., IGFBP2, L1CAM, KT1)35–37 can be considered as potential biomarkers for the diagnosis of CRC.
EFNA1 was originally separated from human umbilical vein endothelial cells as a secretory protein induced by tumor necrosis factor (TNF)38. EFNA1 and its most common receptor, Eph receptor 2 (EPHA2), were associated with various types of cancer, including breast cancer and gastric cancer13,39. In CRC, EFNA1 was highly expressed and showed to be a poor prognostic factor22. However, the role of EFNA1 as a biomarker for cancer diagnosis is rarely studied.
In our study, serum EFNA1 was significantly elevated in 240 CRC patients versus that in 226 healthy controls and showed a good diagnostic ability for CRC with an AUC of 0.715 (95% CI: 0.669–0.761; P < 0.001), specificity of 90.71% and sensitivity of 42.50%. As for the early-stage CRC, a certain diagnostic value could be observed as well, with an AUC of 0.660, a sensitivity of 38.46%, and a specificity of 90.71%. Considering that serum biomarker test is a kind of screening requiring high sensitivity to reduce false negatives, the sensitivity of the EFNA1 test might limit the clinical application in screening purposes in general or high-risk individuals. The combination of multiple biomarkers has been proved to improve the specificity and sensitivity of diagnosis37,40. In future studies, we will seek biomarkers of high sensitivity and specificity for further optimization with the test of serum EFNA1.