Abstract
Pancreatic cancer (PC) is difficult to detect in the early stages; thus, identifying specific and sensitive biomarkers for PC diagnosis is crucial, especially in the case of early-stage tumors. Circulating microRNAs are promising non-invasive biomarkers. Therefore, we aimed to identify non-invasive miRNA biomarkers and build a model for PC diagnosis. For the training model, blood serum samples from 63 PC patients and 63 control subjects were used. We selected 39 miRNA markers using a smoothly clipped absolute deviation-based penalized support vector machine and built a PC diagnosis model. From the double cross-validation, the average test AUC was 0.98. We validated the diagnosis model using independent samples from 25 PC patients and 81 patients with intrahepatic cholangiocarcinoma (ICC) and compared the results with those obtained from the diagnosis using carbohydrate antigen 19-9. For the markers miR-155-5p, miR-4284, miR-346, miR-7145-5p, miR-5100, miR-661, miR-22-3p, miR-4486, let-7b-5p, and miR-4703-5p, we conducted quantitative reverse transcription PCR using samples from 17 independent PC patients, 8 ICC patients, and 8 healthy individuals. Differential expression was observed in samples from PC patients. The diagnosis model based on the identified markers showed high sensitivity and specificity for PC detection and is potentially useful for early PC diagnosis.
Highlights
Pancreatic cancer (PC) is one of the leading causes of cancer-related mortality, as the symptoms of PC seldom appear in the early stages of the disease, and the cancer is mostly detected after it has metastasized to other organs
When 103 miRNAs were used in the principal component analysis (PCA), the 63 PC samples and 29 non-cancer samples were welldistinguished compared to when all miRNAs were used
If we used only non-cancer samples as controls, the biomarkers led to many false positives
Summary
Pancreatic cancer (PC) is one of the leading causes of cancer-related mortality, as the symptoms of PC seldom appear in the early stages of the disease, and the cancer is mostly detected after it has metastasized to other organs. PC is higher than 37%, based on patients diagnosed with pancreatic cancer between 2009 and 2015 [1]. The most effective strategy for reducing PC-related mortality is early diagnosis and treatment. The lack of reliable markers for PC detection reduces the efficacy of screening strategies in at-risk populations, such as those with chronic pancreatitis [2]. Carbohydrate antigen 19-9 (CA19-9) and carcinoembryonic antigen (CEA) are the most commonly used serological biomarkers; they lack sufficient sensitivity and specificity for the detection of PC [3]. To improve the prognosis of patients with this form of cancer, it is important to identify diagnostic biomarkers for PC
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