Scientific REPoRTS | 7: 16796 | DOI:10.1038/s41598-017-17004-x
Blood Serum Calorimetry Indicates
the Chemotherapeutic Ecacy in
Lung Cancer Treatment
, Izabela Chmielewska
, Anna Michnik
& Piotr Zarzycki
Chemotherapy is a primary treatment for the metastatic lung cancer patients. To select the most
eective combination of drugs, we need an ecient way of assessing tumor response. Here, we showed
that dierential scanning calorimetry (DSC) analysis of blood serum proteins could reveal the patient
response to the treatment. If chemotherapy is eective, serum proteins DSC curve of non-small cellular
lung cancer (NSCLC) case is similar to the those of the healthy individuals. If treatment fails, notable
changes occur in the DSC prole of NSCLC patient’s blood serum. Our preliminary work illustrates how
thermal analysis of changes in the heat capacity of blood serum proteins can provide an insight into
patient response to chemotherapy – the essential information for any successive lung cancer treatment.
Lung cancer remains the leading cause of cancer-related death worldwide
. e high mortality is due to late can-
cer diagnosis, at a stage when the tumor has already spread to other organs (metastasis)
. At this metastatic stage,
treatment options are usually limited to chemotherapy or targeted therapy.
Almost all chemotherapeutic drugs have been designed to inhibit DNA replication or cell division in rapidly
dividing tumor cells. However, these drugs ecacy is dicult to assess during the treatment.
At present, we rely on a frequent radiological scanning (e.g., spiral computed tomography) to determine ther-
apy eectiveness by monitoring changes in tumors distribution and size
. On the other hand, the abundance of
the blood samples makes it attractive to assess chemotherapeutic ecacy based on, for instance, the blood serum
proteins. Unfortunately, it remains a challenge, mostly due to a lack of established lung cancer biomarkers.
Nonetheless, the blood serum proteins contain multiple cancer- and treatment-related signatures. First,
the epigenetic changes associated with cancer manifest themselves in altered type, sequence and structure of
expressed proteins at the cellular level (e.g., overexpression of growth factors and their receptors)
. Second, an
eective chemotherapy reduces the number of cancerous cells, thus reducing the number of abnormally expressed
proteins. Because the alteration of proteins is the cellular/extracellular signature of both malignant DNA altera-
tion and chemotherapeutic drugs action, physicochemical analysis of cellular proteins should in principle allow
one to detect treatment ecacy.
Among recently introduced methods for diagnostics and monitoring of diseases, the dierential scanning
calorimetry (DSC) seems to be the most promising one, regarding serum protein-based diagnosis
. DSC serum
prole shows the heat capacity changes corresponding to the process of proteins unfolding as a function of a
temperature. DSC evidences the absence or failure of protein structure or slight changes in protein stability. e
weakness or stabilization of intermolecular interactions allows tracking of the molecules conformational change
under the inuence of environmental factors. e obtained DSC curve contains information about the ther-
modynamic stability of the most abundant serum proteins (i.e., their melting temperatures T
of denaturation ΔH), protein mixture composition and the compositional changes taking place in the disease
state, intra- and intermolecular interactions, including those related to alteration of protein structure. However,
these data usually need skillful analysis because some of them are not directly available thus dicult to inter-
pret. In applying DSC to blood serum proteins, one typically compares the denaturation curves obtained for a
sick patient with the prole expected for the healthy individuals
. e disease-related alterations of serum
Institute of Physical Chemistry, Polish Academy of Sciences, Kasprzaka 44/52, 01-224, Warsaw, Poland.
Department of Pneumonology, Oncology and Allergology Medical University of Lublin, Jaczewskiego 8, Lublin, 20-
Department of Medical Physics, A. Chełkowski Institute of Physics, Uniwersytecka 4, Katowice, 40-
Silesian Center for Education and Interdisciplinary Research, University of Silesia, 75th Pułku Piechoty
1A, Chorzów, 41-500, Poland.
Energy Geoscience Division, Lawrence Berkeley National Laboratory, 1 Cyclotron
Road, Berkeley, CA, 94720 United States. Correspondence and requests for materials should be addressed to K.K.-K.
Received: 6 July 2017
Accepted: 20 November 2017
Published: xx xx xxxx