Discrimination of leukemias and non-leukemic cancers in blood serum samples of children and adolescents using a Raman spectral model

Abstract

This study aimed to identify the differences presented in the Raman spectrum of blood serum from normal subjects compared to leukemic and non-leukemic subjects and the differences between the leukemics and non-leukemics, correlating the spectral differences with the biomolecules. Serum samples from children and adolescents were subjected to Raman spectroscopy (830 nm, laser power 350 mW; n = 566 spectra, being 72 controls, 269 leukemics, and 225 non-leukemics). Exploratory analysis based on principal component analysis (PCA) of the serum sample’s spectra was performed. Classification models based on partial least squares discriminant analysis (PLS-DA) were developed to classify the spectra into normal, leukemic, and non-leukemic, as well as to discriminate spectra of leukemic from non-leukemic. The exploratory analysis showed principal components with peaks related to amino acids, proteins, lipids, and carotenoids. The spectral differences between normal, leukemic, and non-leukemic showed features assigned to proteins (serum features), amino acids, and carotenoids. The PLS-DA model classified the spectra of the normal group versus leukemic and non-leukemic groups with accuracy of 66%, sensitivity of 99%, and specificity of 57%. The PLS-DA discriminated the spectra of the leukemic and non-leukemic groups with accuracy of 67%, sensitivity of 72%, and specificity of 60%. The study showed that Raman spectroscopy is a technique that may be used for the biochemical differentiation of leukemias and other types of cancer in serum samples of children and adolescents. Nevertheless, building an extensive data library of Raman spectra from serum samples of controls, leukemics, and non-leukemics of different age groups is necessary to understand the findings better.

Identification of blood cell changes in pediatric oncological patients through Raman spectroscopy

“…PCA applied to Raman spectra showed accuracy of 91% and specificity of 100%, as all normal B cell samples were correctly classified. Recently, Lima et al 36 used PLS-DA to discriminate blood serum samples of normal children and adolescents from those with leukemia and nonleukemic cancers, showing accuracy of 66%, sensitivity of 99% and specificity of 57%; they presented more misclassifications compared to the ones found in the present study.…”

“…With regard the recent advances of Raman spectroscopy aiming at cancer diagnosis, 8,18,36,43 the direct application of…”

“…7,12,17,18,20 Raman spectroscopy is a promising technique for diagnosing and monitoring cancer, as it is a non-destructive and information-rich technique, offering perspectives to supplement existing diagnostic techniques, detecting early stages of cancer and monitoring the medicines used in the treatment. 18,20,22,[25][26][27][28][29][30][31][32][33][34][35][36][37][38][39][40][41][42][43] From the results presented and the existing literature, one can conclude that Raman spectroscopy and PLS discrimination may be an important technique to help the differentiation and diagnosis of cancerous samples using blood cell samples, showing promising results when differentiating normal (healthy) individuals from ones with leukemia and other types of cancer (sarcoma, blastoma, and lymphoma + carcinoma).…”

“…5 Raman spectroscopy is capable of generating detailed information about the biochemical changes of molecules that occur with the progression of diseases, so it appears as a promising tool for the diagnosis of various pathologies by using near-infrared excitation (e.g., 830 nm) that reduces the autofluorescence that occurs in biological species. 5,6 Raman spectroscopy has been used to identify biomarkers that can provide information about presence of viral infection in serum 7 and can discriminate between different types of cancerous tissues, 8,9 seek for differentiation of cancer from normal tissues through analysis of saliva, 10 quantify cellular water levels, 11 and analyze skin samples in vivo and ex vivo [12][13][14][15][16][17] and whole blood, serum, and blood cells samples [18][19][20][21][22][23][24][25][26][27][28][29][30][31][32][33][34][35][36] aiming at diagnosis, with promising results.…”

“…Raman spectroscopy has been studied as a tool for the differential diagnosis of leukemias, [18][19][20][21][22][23][24][25][26][27][28][29][30][31][32][33][34][35][36] as it has shown great ability to identify spectral information regarding blood cells and biochemical compounds present in the blood such as proteins, amino acids, nucleic acids, lipids, and carotenoids, 16,[18][19][20][21] allowing differentiate the stages of cell maturation. [22][23][24] Raman spectroscopy has been used for the discrimination of neoplastic cells (leukemia) from normal cells 18,20,21,[25][26][27][28][29][30][31][32][33][34][35][36][37][38][39][40][41][...…”