Advances in Proteomic Strategies toward the Early Detection of Lung Cancer

Abstract

TennesseeSince the advent of the new proteomics era more than a decade ago, large-scale studies of protein profiling have been exploited to identify the distinctive molecular signatures in a wide array of biological systems spanning areas of basic biological research, various disease states, and biomarker discovery directed toward therapeutic applications. Recent advances in protein separation and identification techniques have significantly improved proteomics approaches, leading to enhancement of the depth and breadth of proteome coverage. Proteomic signatures specific for invasive lung cancer and preinvasive lesions have begun to emerge. In this review we provide a critical assessment of the state of recent advances in proteomic approaches and the biological lessons they have yielded, with specific emphasis on the discovery of biomarker signatures for the early detection of lung cancer.Keywords: proteomics; biomarker; early detection; lung cancer CHALLENGES IN LUNG CANCER RESEARCHLung cancer is the deadliest cancer in the United States and worldwide, accounting for 15% of all cancer incidence and 29% of all cancer deaths, with a 5-year survival rate of only 15% (1, 2). Lung cancer represents a spectrum of diseases with tremendous heterogeneity at the pathological and molecular levels (3-6) that is strongly associated with smoking as a risk factor. With about 20% of the United States adult population smoking and 1 billion smokers worldwide, it was estimated that in 2009 lung cancer claimed more lives than breast, prostate, colon, liver, kidney, and melanoma cancers combined (2, 7). Despite the recent improvements of bronchoscopic and surgical techniques as well as advances in chemotherapy and radiation therapy treatments, attempts to improve patient outcomes are faced with immense challenges. Several noninvasive detection technologies have been investigated. Imaging techniques, such as chest radiography, lowdose spiral computed tomography, sputum cytology, and molecular biomarkers in various biological samples, have been tested for their diagnostic value for early detection of lung cancer (8, 9). Although these tests vary in their sensitivity and specificity, only low-dose chest computed tomography was shown to reduce lung cancer-specific mortality (10-12). This encouraging finding calls for new molecular strategies to address the noninvasive diagnostic and risk assessment for lung cancer. These molecular strategies will have to demonstrate clinical utility and may complement currently tested strategies. NATURAL HISTORY OF LUNG CANCER PROGRESSION AND A WINDOW FOR EARLY DETECTIONLung cancer can be considered to result from a long history of repeated airway damage and repair cycles. Although clinically addressed at the time of diagnosis, the disease process develops for months and years before affecting patients' lives. This rather long disease process (Figure 1) represents a window of opportunity where the intervention should take place with the aim of preventing the development of disease (e.g., primary preven...

Plasma lipid biomarker signatures in squamous carcinoma and adenocarcinoma lung cancer patients

“…To date the large majority of these biomarkers have been identified as peptides or proteins. Proteomic analytical techniques (Yanagisawa et al 2003, Hassanein et al 2011 have been used in the study of lung cancer, and this has yielded protein biomarkers that have been demonstrated to have high specificity in a study of 54 individuals diagnosed with NSCLC (Zeng et al 2011). Serologic biomarkers of lung cancer have emerged recently: these include carcinoembryonic antigen, the cytokeratin 19 fragment CYFRA21-1, cancer antigen CA-125 (Cedres et al 2011), plasma kallikrein (Chee et al 2008), progastrin-releasing peptide (ProGRP), and neuron-specific enolase (NSE) (Wojcik et al 2008).…”

Important Clues of Current Phosphoproteomic Approaches for Clinical Research

“…Comparative/quantitative analysis of highquality clinical biospecimen (e.g., tissue and biofluids) of human cancer proteome landscape can potentially reveal protein/peptide biomarkers responsible for this disease by means of their altered levels of expression, PTMs as well as diff erent forms of protein variants. Despite technological advances in proteomics, major hurdles still exist at every step of the bio marker development pipeline [52][53][54][55][56][57][58][59][60][61][62][63].…”

Normalization of mass spectrometry data (NOMAD)

“…In addition to understanding roles of metabolites and signaling molecules (Anderson et al, 2016; Sakane et al, 2017), proteome wide identification and quantification of proteins is considered pivotal for elucidating mechanisms underlying biological systems and pathological states (Bantscheff et al, 2012; Hassanein et al, 2011). For this purpose tandem mass spectrometry (MS/MS)-based quantification using isobaric labels such as isobaric tags for relative and absolute quantification (iTRAQ) (Ross et al, 2004) and tandem mass tags (TMT) (Thompson et al, 2003) were introduced (we will refer to these as isobaric tags below).…”