Bladder Cancer Diagnosis from Bladder Wash by Fourier Transform Infrared Spectroscopy as a Novel Test for Tumor Recurrence: Beyond the Abstract
Moreover, patients are required to undergo cystoscopy frequently in the follow-up period. Urine cytology is a morphology-based test that investigates the presence of malignant cells in the bladder wash or urine sediment. The test is useful for determination of high grade malignancies and carcinoma in situ (CIS) [2]. Although the urine cytology has been commonly used in bladder tumor diagnosis, it has 35% median sensitivity and 94% median specificity [3]. Interpretation of the biopsy and cytology results can be highly subjective and there are inconsistencies between the results of different pathologists, and even between the different results of the same pathologist. Cystoscopy combined with urine cytology, still retains its status as a gold standard in the detection of the bladder tumor [4]. Therefore, other non-invasive methods are needed to be developed for the diagnosis of bladder cancer.
Each molecule will have its own unique vibrational characteristics and therefore each molecule will show a unique infrared spectrum. It is for this reason that Infrared (IR) spectroscopy has been an invaluable tool in the characterization of molecular structure and function. IR spectroscopy as an analytical technique, elucidates qualitative and/or quantitative information and provides rapid accurate, reproducible, cost effective and operator independent determination of the spectral differences that occur for example due to pathological or environmental conditions [5]. Spectroscopy-based methods generally yield massive data which require multidimensional multivariate analyses in order to extract specific and meaningful information. Unsupervised multivariate analysis methods like PCA (Principle Component Analysis) and HCA (Hierarchical Cluster Analysis); enable the researcher to explore data without preliminary information about the sample of interest and thus serve as an easy and practical approach [6]. Applying chemometric methods to spectral data enhances the power of Infrared spectroscopy in disease diagnosis [5].
Current study aims to reveal the power of IR spectroscopy coupled with chemometrics, as a non-invasive, observer-independent, rapid and sensitive technique, in the detection of bladder tumor recurrence from bladder wash samples that are routinely collected during cystoscopy.
A total of 136 patients were recruited to the study. IR spectroscopic experiments were carried out as a blind study, the classification results of which were then compared with those of cytology and cystoscopy. Firstly, a set of samples belonging to the control (n=34) and bladder cancer (n=37 consisting of n=22; carcinoma, n=9; papilloma, n=6; PUNLMP) groups were studied using the transmittance mode of infrared spectroscopy. After achieving successful differentiation of the groups, to develop a more rapid diagnostic tool and check the reproducibility of the results, the work was continued with different samples; control (n=21) and bladder cancer (n=44 consisting of n=40; carcinoma, n=2; papilloma, n=2; PUNLMP) using the reflection mode (ATR) of IR spectroscopy by a different operator.
The results revealed significant alterations in molecular content in the bladder cancer group. Based on the spectral differences, using transmittance FTIR spectroscopy coupled with chemometrics, the diseased group was successfully differentiated from the control. Bladder cancer group was differentiated from the control patients with 89.2 % sensitivity. When only carcinoma group was taken into consideration a sensitivity value of 100% was achieved. Using ATR mode of infrared spectroscopy also revealed successful differentiation with high sensitivity.
In summary, this study showed that:
1) Lipid, protein, carbohydrate and nucleic acid specific vibrations were significantly altered due to the carcinogenesis.
2) The high sensitivity values indicate much better discrimination of the diseased groups from the control when compared to the sensitivity of urine cytology.
3) IR spectroscopy offers quicker and more reliable results than cytology. Because of its high sensitivity, in the follow-up period of bladder tumor patients, a cystoscopy procedure can be eliminated if spectroscopy results are negative.
4) FTIR spectroscopy can enable the early detection of bladder tumor non-invasively and show which bladder tumor patient needs cystoscopy during the follow-up period.
This study proposes Fourier Transform Infrared (FTIR) spectroscopy as a more sensitive, rapid, non-destructive and operator-independent analytical diagnostic method for bladder cancer recurrence from bladder wash than other routinely used urine cytology and cystoscopy methods.
Written by: Seher Gok1, Ozge Z. Aydın1, Yavuz S. Sural2, Ferruh Zorlu2, Ümit Bayol 2, Feride Severcan1*
1Department of Biological Sciences, Middle East Technical University, 06800, Ankara, Turkey.
2Department of Urology, Tepecik Education and Training Hospital, 35110, İzmir, Turkey
*Corresponding author
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