Abstract. Colorectal cancer (CRC) is the third most common malignancy worldwide. Disease progression leads to its spread to other organs, such as the liver, and is associated with higher mortality rates. Early CRC detection is therefore crucial for maximizing the chances of complete cure. The measurement of serum-based tumor biomarkers has shown great potential for the detection of CRC. In this study, we investigated the feasibility of using angiopoietin-like protein 2 (ANGPTL2) as a candidate biomarker for CRC. We first investigated ANGPTL2 expression in 7 CRC cell lines, among which Colo320, NCC-CoCK-115P, Caco-2 and Colo205 exhibited comparatively high ANGPTL2 expression. The serum levels of ANGPTL2 in CRC patients (3.45±1.30 ng/ml) were higher compared with those in healthy controls (2.74±0.64 ng/ml) (P<0.05). A receiver operating characteristic analysis demonstrated that the diagnostic performance of ANGPTL2 was marginally lower compared with that of the established biomarker C-reactive protein, but higher compared with that of carbohydrate antigen 19-9. These results suggested that the simultaneous measurement of ANGPTL2, along with previously established serum biomarkers, may increase the likelihood of early detection of CRC.

Globally, gastric cancer is one of the most common types of cancer and is the second leading cause of cancer‑induced mortality. Early detection of gastric cancer is able to contribute to a reduction of its mortality. For early detection, more specific and sensitive biomarkers than the classic biomarkers, including carcinoembryonic antigen, carbohydrate antigen 19‑9 and C‑reactive protein, are required. The present study focused on the evaluation of the potential of angiopoietin‑like protein 2 (ANGPTL2) as a novel biomarker for gastric cancer. The expression levels of ANGPTL2 in undifferentiated and differentiated gastric cancer cell lines (HGC‑27 and MKN7, respectively) were therefore investigated. Additionally, ANGPTL2 levels in the serum of gastric cancer patients were compared with those of healthy individuals to evaluate the possibility of the protein as a predictive biomarker for gastric cancer. It was established that the expression levels of ANGPTL2 mRNA and protein were higher in undifferentiated HGC‑27 cells than those in differentiated MKN7 cells. In a patient study, it was indicated that the levels of ANGPTL2 in the serum of gastric cancer patients were higher than those in healthy controls. The diagnostic performance of ANGPTL2 was assessed by constructing a receiver operating characteristic (ROC) curve and was evaluated by calculating the area under each ROC curve (AUC). For the discrimination of patients with gastric cancer from healthy individuals, the AUC for ANGPTL2 was 0.774 (P=0.005) (95% confidence interval, 0.615‑0.933). These results suggested that ANGPTL2 was a potential biomarker for gastric cancer.

A relationship between Alzheimer's disease (AD) and folate has been reported. Amyloid positron emission tomography (PET) is currently one of the most reliable biomarkers for AD. We investigated the correlation between serum folate levels and amyloid imaging to clarify whether serum folate could be a biomarker for AD. We also examined the usefulness of a combined assessment of serum folate levels and red blood cell hemoglobin content. Apolipoprotein E (APOE) gene polymorphisms were also assessed. Serum folate levels and hemoglobin content were evaluated by receiver operating characteristic analysis for their diagnostic capability as AD biomarkers relating to brain amyloid β accumulation. The area under the ROC curve (AUC) for serum folate was 0.136 (95% confidence interval [CI]: 0.000–0.312; p = 0.016). The AUC for hemoglobin content was 0.848 (95% CI: 0.661–1.000; p = 0.021). Therefore, the folate deficiency with low folate levels or the non-anaemia with high hemoglobin content levels were found to have a high probability of also testing positive for amyloid. Furthermore, eight patients were found to be folate deficiency and non-anaemia, those who were consist of 7 amyloid positive patients (87.5%), and only one of the amyloid negative patients (12.5%). These results suggest that a deficiency of serum folate and high hemoglobin levels may reflect an increased risk of amyloid β accumulation in the brain. Additionally, we demonstrated that these biomarkers could enhance the effectiveness of APOE as an AD biomarker. This study reveals that the combined assessment of serum folate levels and red blood cell hemoglobin content may be a useful biomarker for amyloid β accumulation in the brain. We also found that the combination of serum folate levels and hemoglobin content is a more specific and sensitive blood biomarker for AD than APOE or folate alone. These findings may be used to support clinical diagnosis of AD using a simple blood test.

Patients showing discrepancies between MRI and SPECT demonstrated intermediate amyloid deposition findings compared with patients who showed typical or atypical findings. Strong white matter signal abnormalities on MRI in patients who presented typical AD findings provided further evidence for the involvement of vascular factors in AD.

Pancreatic cancer is one of the tumors with the worst prognosis, with the 5-year survival rate reported to be 6%. The number of patients suffering from pancreatic cancer in recent years has continued to increase dramatically. Carbohydrate antigen 19-9 is an established biomarker of pancreatic cancer, but it does not have sufficient ability to detect pancreatic cancer at an early stage. We focused on angiopoietin-like protein 2 (ANGPTL2), which has been reported to be related to chronic inflammation and Type 2 diabetes mellitus. In this study, whether ANGPTL2 can detect early pancreatic cancer was evaluated. It was found that the concentration of serum ANGPTL2 was significantly higher in pancreatic cancer patients and tumor stage 0-I patients than in healthy individuals (5.84 ± 1.82 ng/mL vs 3.61 ± 0.64 ng/mL; P < 0.001) (5.68 ± 0.79 ng/mL vs 3.61 ± 0.64 ng/mL; P = 0.010). In addition, the diagnostic capability of serum ANGPTL2 levels for pancreatic cancer was evaluated using receiver operating characteristic (ROC) curve analysis. The area under the ROC curve (AUC) for ANGPTL2 was 0.906 (95% confidence interval (CI): 0.815-0.997; P < 0.001). To identify the risk factors for pancreatic cancer, multivariate regression models were used. Ten factors were included, and increasing age (odds ratio (OR), 1.318, 95% CI, 1.058-1.642; P = 0.014) and high ANGPTL2 levels (OR, 22.219, 95% CI, 1.962-251.659, P = 0.012) were found to be independent risk factors for pancreatic cancer, with ANGPTL2 having the strongest relationship. In addition, serum ANGPTL2 levels were strongly correlated with inflammatory markers, with blood sugar levels showing the strongest correlation with serum ANGPTL2 levels. In conclusion, this study suggested that an elevated serum ANGPTL2 level has the potential to be a biomarker capable of early detection of pancreatic cancer, and it was correlated with inflammation of the pancreas and the risk of developing diabetes mellitus.