Abstract
Recently, we have been seeing emerging applications of non-invasive approaches using serum biomarkers including miRNA and proteins in detection of multiple cancers. Currently, majority of these methods only use solitary type of biomarkers, which often lead to non-satisfactory sensitivity and specificity in clinical applications. To this end, we established a unique biomarker panel in this study, which determined both squamous cell carcinoma antigen (SCC Ag) degree and miRNA-29a, miRNA-25, miRNA-486-5p levels in blood for detection of early-stage cervical cancer. We designed our study with two phases: a biomarker discovery phase, followed by an independent validation phase. In total of 140 early-stage cervical cancer patients (i.e., AJCC stage I and II) and 140 healthy controls recruited in the biomarker discovery phase, we achieved sensitivity of 88.6% and specificity of 92.9%. To further assess the predictive power of our panel, we used it to an independent patient cohort that consisted of 60 early-stage cervical cancer individuals as well as 60 healthy controls, and successfully achieved both high sensitivity (80.0%) and high specificity (96.7%). Our study indicated combining analyses of multiple serum biomarkers could improve the accuracy of non-invasive detection of early-stage cervical cancer, and potentially serve as a new liquid biopsy approach for detecting early-stage cervical cancer.
Highlights
For women worldwide in the world, cervical cancer, which is ranked as the fourth most frequently occurred cancer[1], contributed for 6.6% of the total cases of cancer and 7.5% of the total cancer fatalities of women in 20181
We first recruited a total of 140 early-stage cervical cancer patients as well as 140 healthy controls to discover the panel of biomarkers
We found that using this panel of biomarkers, we could discriminate early-stage cervical cancer patients from healthy controls, achieving high sensitivity of 88.6% and high specificity of 92.9%
Summary
For women worldwide in the world, cervical cancer, which is ranked as the fourth most frequently occurred cancer[1], contributed for 6.6% of the total cases of cancer and 7.5% of the total cancer fatalities of women in 20181. MicroRNAs (miRNAs) were suggested as encouraging biomarkers for non-invasive detection of cervical cancer with high sensitivity and specificity. We were encouraged by the previous successes on using combined analysis of multiple analytes for cancer detection, and aimed to develop a panel of biomarkers that could combine the usage of both miRNA and proteins for detecting cervical cancer at early stages To this end, we first recruited a total of 140 early-stage cervical cancer patients as well as 140 healthy controls to discover the panel of biomarkers (i.e., the initial biomarker discovery phase). We found that our panel of biomarkers could successfully separate early-stage cervical cancer patients from healthy controls at sensitivity of 80.0% and specificity of 96.7% These studies confirmed that the panel of miRNA and protein could serve as an accurate, non-invasive approach for detection of early-stage cervical cancer. Our study represents the first attempt of using both miRNA and protein biomarkers in non-invasive detection of cervical cancer at early stages
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