Exploring ovarian cancer screening using a combined sensor approach: A pilot study

Nicholas Kybert,Emmarose Joffe,Katharine Prokop-Prigge,A T Charlie Johnson,Janos Tanyi,Jody Piltz-Seymour,George Preti,Lorenzo Ramirez,Cynthia M Otto

doi:10.1063/1.5144532

Abstract

All cells release low molecular weight organic compounds that possess finite vapor pressures at body and/or ambient temperatures. These volatile organic compounds (VOCs) may possess an odor and can be found emanating from all body fluids. As cells turn malignant, analysis of changes in these VOCs can provide insight into cancer onset and diagnosis. Previous studies have demonstrated that dogs can be trained to distinguish ovarian cancer tissues of various stages and grades from normal ovarian tissue and other gynecological malignancies with sensitivity and specificity over 95%. When trained on biopsied tissue, dogs were able to detect the VOC disturbances in peripheral blood samples with the same accuracy. Building on these earlier studies, we examined the VOCs emanating from plasma samples from primary ovarian cancer patients, patients with benign reproductive tract growths, and healthy controls. We used a three-pronged sensor approach to analyze the VOCs from plasma: canines trained on tissue and plasma samples, analysis using solid phase microextraction gas chromatography–mass spectrometry, and novel single stranded DNA-coated carbon nanotube sensor field effect transistors. Each of the three experimental approaches used in this study provided preliminary evidence that plasma from ovarian cancer patients emits a volatile odor signature that can be distinguished from the VOCs of patients with benign ovarian tumors and controls. Our results provide optimism that a diagnostic approach based on the analysis of the VOC odor signature of ovarian cancer is achievable.

Highlights

In 2019, it is estimated that there will be 22 530 new cases of ovarian carcinoma in the US, resulting in an estimated 13 980 deaths.1,2 Diagnosis of ovarian cancer is severely hindered by the lack of reliable diagnostic tools, despite the importance of early diagnosis to treatment success
Each of the three experimental approaches used in this study provided preliminary evidence that plasma from ovarian cancer patients emits a volatile odor signature that can be distinguished from the volatile organic compounds (VOCs) of patients with benign ovarian tumors and controls
Our results suggest significant differences in the VOC profile in the pooled blood plasma samples of the patients with ovarian cancer compared to controls and patients with benign ovarian tumors; these differences were confirmed by all three detection methods: trained detection dogs, organic chemical analysis with solid-phase microextraction (SPME)/GAS chromatography/mass spectrometry (GC/MS), and ssDNA-carbon nanotube (CNT) sensors

Summary

Introduction

In 2019, it is estimated that there will be 22 530 new cases of ovarian carcinoma in the US, resulting in an estimated 13 980 deaths. Diagnosis of ovarian cancer is severely hindered by the lack of reliable diagnostic tools, despite the importance of early diagnosis to treatment success. The lack of reliable screening strategies and lack of obvious symptoms associated with early stage ovarian cancer spurred a large scale investigation into screening, sponsored by the NCI: The Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial, which concluded that annual screening for ovarian cancer with transvaginal ultrasound and CA-125 does not reduce disease-specific mortality in women at average risk for ovarian cancer.. The lack of reliable screening strategies and lack of obvious symptoms associated with early stage ovarian cancer spurred a large scale investigation into screening, sponsored by the NCI: The Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial, which concluded that annual screening for ovarian cancer with transvaginal ultrasound and CA-125 does not reduce disease-specific mortality in women at average risk for ovarian cancer.4 Techniques such as transvaginal ultrasound can help find tumors in the ovary, but when used for screening, most of the masses found are non-cancerous There is no sufficient screening test for the accurate and early detection of ovarian cancer in women of average risk. The lack of reliable screening strategies and lack of obvious symptoms associated with early stage ovarian cancer spurred a large scale investigation into screening, sponsored by the NCI: The Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial, which concluded that annual screening for ovarian cancer with transvaginal ultrasound and CA-125 does not reduce disease-specific mortality in women at average risk for ovarian cancer. Techniques such as transvaginal ultrasound can help find tumors in the ovary, but when used for screening, most of the masses found are non-cancerous

Methods

Results

Conclusion