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Lung Cancer Study Points to Possible Blood Metabolomic Markers

NEW YORK – A team from the US and Germany has identified blood metabolites that show promise for distinguishing between the two main forms non-small cell lung cancer in patients with early-stage disease, along with markers that appear to coincide with longer overall survival.

The researchers used high-resolution magnetic resonance spectroscopy to assess chemical compounds in paired blood and tumor samples from almost 100 lung cancer patients with squamous cell carcinoma or adenocarcinoma, as well as blood samples from 29 healthy control individuals. Findings from the proof-of-principle study, appearing online today in Scientific Reports, indicated that blood samples from the NSCLC patients do contain metabolites shared with those found in the tumor.

Moreover, the team reported, the results so far suggest that these metabolite profiles may offer insights into an individual's tumor type, disease stage, and potential survival trajectory. In addition to markers that varied between SCC and adenocarcinomas, for example, the analysis highlighted distinct blood metabolite profiles in NSCLC patients with average overall survival times that exceeded 41.3 months.

"Prolonged survival is associated with relative over-expression of glutamine, valine, and glycine, and relative suppression of glutamate and lipids in serum," the researchers wrote.  

At the moment, the US Preventive Services Task Force recommends yearly screening with low-dose spiral computerized tomography for individuals at elevated lung cancer risk based on their age and smoking history.

Because this approach is expensive, involves some exposure to radiation, and may lead to over-diagnoses, though, it less than ideal for widespread population screening, the team explained. That, in turn, suggests complementary techniques may help to triage individuals to CT scanning as a means of finding additional early-stage lung cancers.

"[W]hat we're trying to do is to develop biomarkers from blood samples that could be incorporated into physical exams, and if there is any suspicion of lung cancer, then we would put the patient through CT," co-senior and co-corresponding author Leo Chang, a biophysics researcher in the Massachusetts General Hospital's radiology and pathology departments, said in a statement.

With that in mind, the researchers used an approach called high-resolution magic angle spinning magnetic resonance spectroscopy (HRMAS MRS) to assess metabolites in matched blood and tumor samples from 42 individuals with SCC and 51 individuals with adenocarcinoma. The participants were part of a larger lung cancer survival study, they noted, and included 27 stage I SCC cases, 31 stage I adenocarcinoma cases and 35 individuals with more advanced stage II, III, or IV NSCLCs.

The team first compared patient blood profiles with metabolite patterns present in blood samples from 29 healthy individuals, uncovering apparent clusters of metabolite differences that were supported by metabolic profiles in corresponding lung tumor samples.

The authors noted that "metabolomic profiles presented by blood serum cannot be expected to mimic those measured from cancerous tissues," though "analyses of the similarities and differences of cancer metabolomic profiles measured from paired tissue and serum samples will improve understanding of cancer metabolism both for patient prognostication and design of treatment strategies."

Through a series of follow-up analyses, the researchers went on to focus in on the most promising potential metabolite markers for tumor type, disease stage, and lung cancer outcome, before dividing the lung cancer patient group into training and testing cohorts to evaluate the proposed markers, particularly those coinciding with overall survival.

"While the leave-one-group-out analyses indicated the potential existence of metabolomic discriminators between short and prolonged [lung cancer] patient survival, the method cannot provide a single set of parameters able to evaluate the status of a future case," the authors cautioned.

Even so, "this proof of the potential existence of the survival-related intrinsic [lung cancer] metabolomics encouraged us to further analyze all cases in a single data set," they wrote, noting that across all 93 lung cancer cases "we identified nine serum spectral regions that show significant differentiation between short and prolonged survival groups."