Elsevier

Vibrational Spectroscopy

Volume 105, November 2019, 102982
Vibrational Spectroscopy

Monitoring of breast cancer patients under pre and post treated conditions using Raman spectroscopic analysis of blood plasma

https://doi.org/10.1016/j.vibspec.2019.102982Get rights and content

Abstract

This study is aimed to monitor the therapeutic response in breast cancer patients, by using the Raman spectra of liquid blood plasma of biopsy proved 19 breast cancer patients under pre and post treatment conditions and also by comparing them with the spectra of control group, consisting of 26 normal subjects (with no significant history of illness) in the same age group. The results indicate that there exists a statistical significance in the spectral signatures between the normal and breast cancer patient’s blood plasma as well as between pre treated and post treated plasma, which may be attributed to the changes in the vibrational characteristics of some of the key biomolecules viz tyrosine, phenylalanine, methionine, tryptophan, lipids/phospholipids, amides, DNA base pairs(adenine and guanine) etc. Further, it is found that the spectral signatures of post treated plasma (after completion of the entire course of treatment) are almost matching with that of normal subjects. The results of the study indicates the possibility of using Raman Spectroscopy for diagnosis as well as for monitoring of treatment response in breast cancer patients.

Introduction

Despite the advancements in medical technology, the occurrences and the deaths due to cancers continue to be a matter of concern globally. Among various cancers, breast cancer is the commonest cancer diagnosed among women worldwide (almost 154 countries) and is the leading cause of cancer related transience in women [1]. Many diagnostic methods have been adopted for the early detection of cancers with an aim of achieving better survival. In this context, molecular diagnostics using various optical spectroscopic techniques including Raman spectroscopic analysis of cells, tissues and bio fluids have also been considered by the researchers due to the development of sophisticated optoelectronic devices. Alfano et al., initiated the use of Raman spectroscopy (RS) in the discrimination of malignant breast tissue from normal breast tissue as early as 1991 [2]. The possibility of rapid diagnosis of Breast Cancer with RS using a fiber optic tissue sampling with a core biopsy needle was demonstrated by Richard Mc Creery [3]. Daniel et al.,had also reported on Raman mapping of oral tissues for cancer diagnosis [4]. Although many key bio molecules present in the cells and tissues are considered as markers to detect various disorders and diseases, the study of biomolecules present in bio fluids and in particular blood plasma has gained importance because of having many metabolic end products of cells /tissues in the circulating blood and ease of sample collection process with minimally invasive procedures. In this context, Qi Wei et al., had reported on characterization of liver cancers using RS of human serum [5]. Pichardo-Molina et al., had worked on RS and multivariate analysis of serum samples in the discrimination of Breast cancer [6]. Harris et al., have also established the feasibility of using RS in cancer screening through a peripheral blood sample [7]. Rekha et al has also reported on Near infrared RS characterization of blood plasma of normal, oral premalignant and malignant conditions [8] and Obeita et al., had reported on Surface Enhanced RS of serum samples in the discrimination of Breast cancers and had established appreciable results [9].

Even though there are a number of groups working on the discrimination of cancer and its early diagnosis, more emphasis need to be given to management of malignancies and especially assessment of the response to the treatment so as to produce better patient outcomes. Conventionally, therapeutic response of various treatment modalities like chemotherapy, radiotherapy and surgery are assessed by histopatholoical methods (invasive), biochemical assays and through various imaging modalities including nuclear medicine imaging techniques. As far as breast cancer patients are concerned, most of the breast cancer patients undergo surgery as the primary modality of treatment wherein, measurable and macroscopic disease is removed and the microscopic residue is being tackled by chemotherapy and radiotherapy (based on the histopathology of the surgical specimen) and hence it is difficult to get tissue samples after the completion of the entire course of treatment, for comparison and assessment of treatment efficacy. It is to be noted that the American society of Clinical Oncology have mentioned in their report that the clinical data are insufficient to recommend the use of serum based tumor markers (CA 15-3, CA 27–29) for cancer screening, diagnosis, staging and also for monitoring patients for recurrence after primary breast cancer therapy and suggests other complimentary techniques to be considered along with tumor markers [10]. There exists a need for minimally invasive and less expensive techniques for monitoring of cancer patients which unwrap opportunities for researchers in the field on oncology. In this context, Raman spectroscopic analysis is being exploited by researchers to evaluate the treatment response in cancer patients as RS techniques do not require sample preparation. Haka et al., studied the marginal assessment of tissue during partial mastectomy in breast cancer patients using RS [11]. Abramczyk et al., worked on the use of RS in the diagnosis and treatment of breast cancer [12]. Potcoava et al., reported on the changes due to hormone treatment in breast cancer cells using Raman and anti Raman Stokes scattering microscopy [13]. Hossain et al., monitored the uptake and release of chemo drug doxorubicin in cell cultures using surface enhanced RS [14]. Depciuch et al., studied the Raman spectra of tissue samples obtained from breast cancer patients before and after neo adjuvant chemotherapy which showed changes in amounts of carotenoids and fats. They also observed changes in carbohydrate and protein levels in comparison with normal breast tissues [15]. However, only minimal literature is available on the use of RS of biofluids in the monitoring of breast cancer patients. The goal of this pilot study is to explore the use of RS techniques in the characterization of liquid blood plasma of breast cancer patients and also to assess the therapeutic response based on the variations exhibited in the spectra of breast cancer plasma under pre and post treated conditions. It is certain that this study would facilitate identification of reliable biomarkers, for understanding the tumor response to therapy, thus leading to improved survival.

Section snippets

Samples- classification and protocol

The study group consisted of 19 female breast cancer patients (male Breast cancers not included in the study, considering the low prevalence)in the age group of 40-55years, with biopsy proved Infiltrating ductal carcinoma, with known Immunohistochemistry status from tissue sample (ER/ PR/ EGFR/ VEGFR/ HER2neu/ E-Cadherin/ KI67) and recorded values of Tumour markers (CEA, CA15/3). The liver and renal functions along with cardiac status were analysed and recorded for all the patients belonging to

Results of the spectral analysis

Raman spectra of plasma of all the cases belonging to the study were measured in the wavenumber region from 200–1800 cm−1. To eliminate the possible errors arising during the process of spectral acquisition, the measured raw spectra were subjected to intensity correction, baseline correction and smoothening. Even though the entire acquired spectra exhibits considerable variations in the Raman spectral signatures of blood plasma between the healthy normal subjects and the breast cancer patients

Discussion

Even though early diagnosis of cancer is essential for improved survival, it is also equally important to monitor the therapeutic efficacy for effective cancer management. Though several diagnostic modalities which include nuclear/non nuclear sate of the art techniques such as Positron Emission Tomography (PET) scan combined with Computerized Tomography (CT) or Magnetic Resonance Imaging (MRI) are being employed for the diagnosis of cancer, to know the metastatic status of the disease as well

Conclusion

Considering the global breast cancer incidence and mortality rate, there arises an urgent need for establishing simple and affordable treatment monitoring techniques, to facilitate tailored treatment protocols for better survival. The present pilot study conducted using RS techniques combined with statistical analysis, to study the variations between pre and post treated breast cancer patients by identifying the subtle pathological/metabolic variations occurring in cancer patients undergoing

Funding

The work was supported by the Board of Research in Nuclear Sciences, Department of Atomic Energy, Government of India (Grant No. 2009/34/38/BRNS/3206).

Conflict of interest

None.

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