The Convergence of FTIR and EVs: Emergence Strategy for Non-Invasive Cancer Markers Discovery

In conjunction with imaging analysis, pathology-based assessments of biopsied tissue are the gold standard for diagnosing solid tumors. However, the disadvantages of tissue biopsies, such as being invasive, time-consuming, and labor-intensive, have urged the development of an alternate method, liquid biopsy, that involves sampling and clinical assessment of various bodily fluids for cancer diagnosis. Meanwhile, extracellular vesicles (EVs) are circulating biomarkers that carry molecular profiles of their cell or tissue origins and have emerged as one of the most promising biomarkers for cancer. Owing to the biological information that can be obtained through EVs' membrane surface markers and their cargo loaded with biomolecules such as nucleic acids, proteins, and lipids, EVs have become useful in cancer diagnosis and therapeutic applications. Fourier-transform infrared spectroscopy (FTIR) allows rapid, non-destructive, label-free molecular profiling of EVs with minimal sample preparation. Since the heterogeneity of EV subpopulations may result in complicated FTIR spectra that are highly diverse, computational-assisted FTIR spectroscopy is employed in many studies to provide fingerprint spectra of malignant and non-malignant samples, allowing classification with high accuracy, specificity, and sensitivity. In view of this, FTIR-EV approach carries a great potential in cancer detection. The progression of FTIR-based biomarker identification in EV research, the rationale of the integration of a computationally assisted approach, along with the challenges of clinical translation are the focus of this review.