Lung cancer diagnosis typically involves a physical examination, imaging and procedures such as a bronchoscopy or a biopsy to obtain samples. Pathologists analyze tumor specimens to determine cancer histology and conduct molecular testing to identify specific gene mutations and rearrangements. This information helps clinicians identify the best therapy for each individual.

Dr. Maria Uribarri and her team published a paper in the Journal of Thoracic Oncology2 that may have implications for lung cancer diagnosis. The aim of their study was to identify and validate diagnostic biomarkers for early detection and subtype classification of lung cancer. Here is a summary of their four key findings:

  • Bronchoalveolar lavage produces an acceptable sample for lung cancer analysis. Samples are obtained during flexible bronchoscopy, and involve flushing a part of the lung with fluid to harvest surrounding cells. This method is widely used to diagnose infections and lung diseases such as asthma or sarcoidosis, but only recently has it been used to obtain lung cancer samples. This paper shows that bronchoalveolar lavage – which is far less invasive than a biopsy — is a sufficient source of materials for analysis.
  • Using high throughput molecular techniques, the team identified 32 candidate biomarkers. The researchers analysed bronchoalveolar lavage samples from 139 lung cancer patients and 49 patients with non-malignant pulmonary diseases including pneumonia, bronchitis, sarcoidosis and chronic bronchopathy. The team identified differentially expressed proteins using 2D polyacrylamide gel electrophoresis followed by mass spectrometry. All 32 candidate biomarkers participate in biological functions known to be dysregulated in cancer development. Thirteen of these biomarkers were not previously associated with lung cancer, including seven that have never been detected in human bronchoalveolar lavage, and may represent therapeutic targets in this disease.
  • The team validated nine lung biomarkers using immunoassays. Of the 32 proteins identified, those with a 2-fold change or greater were tested in a validation assay using a different set of bronchoalveolar lavage samples (204 from lung cancer patients and 48 from controls). Nine biomarker proteins were validated including APOA1 (apolipoprotein A-1), CO4A (complement C4A), CRP (C-reactive protein), GSTP1 (glutathione S-transferase P), SAMP (serum amylid P-component), HPT (haptoglobin), PRDX2 (peroxiredoxin-2), AMBP (protein AMBP), and PUR6 (multifunctional protein ADE2). Four biomarkers differed between small-cell lung cancer and non-small cell lung cancer subtypes: CPR, GSTP1, SAMP and STMNI (stathmin). Importantly, all biomarkers already showed significant expression differences between early stage lung cancer and control cells, meaning that they have the potential to indicate disease early.
  • The team developed a diagnostic biomarker panel for lung cancer with five biomarkers and tested whether they could diagnose lung cancer. The diagnostic panel consisted of biomarkers APOA1, CO4A, CRP, GSTP1 and SAMP. This panel reached 95% sensitivity and 81% specificity (0.94 AUG) and was able to correctly classify 38 of 46 control patients and 168 of 177 lung cancer patients, proving its utility as a complementary diagnostic tool. The differential expression of STMN1 and GSTP1 proteins allowed the two main lung cancer types to be discriminated with 90% sensitivity and 57% specificity (0.80 AUC). In the discussion, the researchers speculate that the five-gene biomarker panel might be used for serum-based detection. An assay like this would enable an easier and earlier diagnosis of lung cancer, resulting in better outcomes.
  1. Uribarri, M, Hormaeche, I, Zalacain R et al. A new biomarker panel in bronchoalveolar lavage for an improved lung cancer diagnosis. J Thorac Oncol. 2014 Oct;9(10):1504-12. doi: 10.1097/JTO.0000000000000282.