Page 12 - TD-3-2

Tumor Discovery Volatile organic compounds for cancer screening

Thus, there is an unmet need for a reliable, non- Given the intrinsic limitations of stool-based screening,
invasive screening test for colon cancer. The analysis colonoscopy remains the gold standard for the detection
of VOCs in exhaled breath has been applied to colon of pre-cancerous adenomas and the recommended
cancer, and while data remain sparse, studies have evaluation following an abnormal stool-based screening
identified several potential metabolic biomarkers. test. It is an invasive test associated with patient discomfort,
Indeed, predictive models using combinations of 4 – procedural risks, and suboptimal compliance. In contrast,
60 VOCs have been shown to be comparable to both early detection of colon cancer through VOC analysis
colonoscopy and stool-based screening for the detection would allow for non-invasive, inexpensive, and accessible
of colon cancer (Figure 2). However, while the individual screening. VOC analysis may also be superior in sensitivity
molecules described may not be specific to colon cancer, and specificity when compared to screening colonoscopy.
the expression patterns are diagnostic, leading to the
description of validated “breathprints,” which combine 4. Prostate cancer
clusters of exhaled VOCs. Despite being the second most prevalent malignancy in
Wang et al., using solid-phase microextraction-GC/ men worldwide, there are currently no reliable screening
35
MS, described increased levels of cyclohexanone, tools for prostate cancer. 38-40 Prostate cancer is the third-
2,2-dimethyldecane, dodecane, 4-ethyl-1-octyn- leading cause of new cancer cases diagnosed worldwide,
3-ol, ethylaniline, cyclooctylmethanol, trans-2- with approximately 1.4 million new cases diagnosed
39
dodecen-1-ol, and 3-hydroxy-2,4,4-trimethylpentyl in 2020. At present, a combination of digital rectal
2-methylpropanoate (P < 0.05) in the exhaled breath of examination, serum prostate-specific antigen (PSA), and
patients with colon cancer. The biological significance trans-rectal ultrasound-guided prostate biopsy is employed
of these molecules remains unclear. The authors for prostate cancer. 38-41
hypothesize that malignancy is associated with increased Serum PSA, at a cut-off of 4 ng/mL, was integrated into
oxidative stress and lipid peroxidation, which may screening programs in the United States of America in the
explain the patterns of VOC expressed in the exhaled 1990s. 38-44 However, due to a sensitivity as low as 21% for
breath of patients with colon cancer. Phillips et al. 12,19,24 prostate cancer and 51% for high-grade cancers, the use
25
published several analyses of VOC patterns expressed in of PSA for cancer screening is no longer recommended
various malignancies, which further support the theory in most international screening guidelines (Figure 1). 40-46
that alkanes and alkane-derivatives in exhaled air may be Indeed, two large screening trials failed to demonstrate a
associated with increased cytochrome P450 activity and significant decrease in prostate cancer-associated mortality
increased oxidative stress. using PSA-based screening tests. 46,47 Moreover, with a
Altomare et al. demonstrated the relationship between false-positive rate as high as 20%, PSA screening has
36
the presence of malignancy and expressed VOCs. They been associated with significant overdiagnosis as well as
discovered that a combination of 11 VOCs was diagnostic subsequent unnecessary testing/biopsies. 38-46
for colon cancer, with a sensitivity of 100%, a specificity of Liu et al. utilized a combination of 86 VOCs in a
47
97.92%, and an overall accuracy of 98.75% (Figure 2). The cohort of 43 patients with a definite pathological diagnosis
same VOC pattern discriminated between patients with of prostate cancer and 64 controls, whereby their model
a history of colon cancer who had been disease free for accurately detected prostate cancer with a sensitivity
over a year and healthy controls with a sensitivity of 100%, of 87.0% and a specificity of 91.3% (AOC = 0.945).
specificity of 90.91%, and accuracy of 94.25%. In another Specifically, furan-3-methanol, (e,e)-octadeca-2,4-dienal,
26
similar study, 418 breath samples were collected from 2-ethylhexan-1-ol, and 2-undecen-1-al were most specific
65 patients with colon cancer, as well as 22 with adenomas, in differentiating cancer specimens from controls, with
and 122 non-cancer control cases. Using GC-MS analysis AUCs >0.70. Similarly, Gao et al. measured the VOC
48
to detect four compounds of interest (acetone, ethyl acetate, profile of the urine headspace through GC-MS in a test
ethanol, and 4-methyl octane), patients with colon cancer cohort of 108 patients with biopsy-confirmed prostate
were distinguishable from controls with 85% sensitivity, cancer positives and compared them to controls, creating a
94% specificity, and 91% accuracy (Figure 1). Their model diagnostic model with 11 VOCs, which they subsequently
37
also distinguished between advanced and non-advanced validated with another group of test samples, which
adenomas with 88% sensitivity, 100% specificity, and 94% included 53 patients with prostate cancer compared to 22
accuracy. As such, VOC analysis offers an advantage over healthy controls, with a resulting AUC of 0.86. Following
stool-based screening in its ability to accurately detect pre- cross-validation, the AUC for this model was 0.92
cancerous adenoma. 37 (sensitivity = 0.96; specificity = 0.80) (Figure 1). 48

Volume 3 Issue 2 (2024) 6 doi: 10.36922/td.2061