Metabolic Alterations in Sputum and Exhaled Breath Condensate of Early Stage Non-Small Cell Lung Cancer Patients After Surgical Resection: A Pilot Study

Naseer Ahmed; Biniam Kidane; Le Wang; Zoann Nugent; Nataliya Moldovan; April McElrea; Shiva Shariati-Ievari; Gefei Qing; Lawrence Tan; Gordon Buduhan; Sadeesh K Srinathan; Renelle Meyers; Michel Aliani

doi:10.3389/fonc.2022.874964

Metabolic Alterations in Sputum and Exhaled Breath Condensate of Early Stage Non-Small Cell Lung Cancer Patients After Surgical Resection: A Pilot Study

Front Oncol. 2022 Jun 3:12:874964. doi: 10.3389/fonc.2022.874964. eCollection 2022.

Authors

Naseer Ahmed^{1

2}, Biniam Kidane^{1

3

4}, Le Wang^{5

6}, Zoann Nugent⁵, Nataliya Moldovan², April McElrea⁶, Shiva Shariati-Ievari⁶, Gefei Qing⁷, Lawrence Tan⁴, Gordon Buduhan⁸, Sadeesh K Srinathan⁴, Renelle Meyers⁹, Michel Aliani^{6

10}

Affiliations

¹ CancerCare Manitoba Research Institute, Winnipeg, MB, Canada.
² Department of Radiology, Section of Radiation Oncology, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, MB, Canada.
³ Department of Physiology and Pathophysiology, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, MB, Canada.
⁴ Department of Surgery, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, MB, Canada.
⁵ Department of Epidemiology and Cancer Registry, CancerCare Manitoba, Winnipeg, MB, Canada.
⁶ St. Boniface Hospital Albrechtsen Research Centre, Winnipeg, MB, Canada.
⁷ Department of Pathology, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, MB, Canada.
⁸ Department of Surgery, University of British Columbia, Vancouver, BC, Canada.
⁹ BC Cancer Research Institute, University of British Columbia, Vancouver, BC, Canada.
¹⁰ Department of Food and Human Nutritional Sciences, University of Manitoba, Winnipeg, MB, Canada.

Abstract

Every year, close to two million people world-wide are diagnosed with and die of lung cancer. Most patients present with advanced-stage cancer with limited curative options and poor prognosis. Diagnosis of lung cancer at an early stage provides the best chance for a cure. Low- dose CT screening of the chest in the high-risk population is the current standard of care for early detection of lung cancer. However, CT screening is invasive due to radiation exposure and carries the risk of unnecessary biopsies in non-cancerous tumors. In this pilot study, we present metabolic alterations observed in sputum and breath condensate of the same population of early- stage non-small cell lung cancer (NSCLC) patients cancer before and after surgical resection (SR), which could serve as noninvasive diagnostic tool. Exhaled breath condensate (EBC) (n=35) and sputum (n=15) were collected from early-stage non-small cell lung cancer (NSCLC) patients before and after SR. Median number of days for EBC and sputum collection before and after SR were 7 and 42; and 7 and 36 respectively Nuclear magnetic resonance (NMR) and liquid chromatography quadrupole time-of-flight mass spectrometry (LC-QTOF-MS) were used to analyze the metabolic profile of the collected samples. A total of 26 metabolites with significant alteration post SR were identified, of which 14 (54%) were lipids and 12 constituted nine different chemical metabolite classes. Eighteen metabolites (69%) were significantly upregulated and 8 (31%) were downregulated. Median fold change for all the up- and downregulated metabolites (LC-QTOF-MS) were 10 and 8, respectively. Median fold change (MFC) in concentration of all the up- and downregulated metabolites (NMR) were 0.04 and 0.27, respectively. Furthermore, glucose (median fold change, 0.01, p=0.037), adenosine monophosphate (13 log fold, p=0.0037) and N1, N12- diacetylspermine (8 log fold p=0.011) sputum levels were significantly increased post-SR. These identified sputa and EBC indices of altered metabolism could serve as basis for further exploration of biomarkers for early detection of lung cancer, treatment response, and targets for drug discovery. Validation of these promising results by larger clinical studies is warranted.

Keywords: cancer; lung; metabolism; resection; surgical.