Role of a serum‐based biomarker panel in the early diagnosis of lung cancer for a cohort of high‐risk patients

Abstract

BACKGROUND: This study applied a combined cancer biomarker panel to clinically identify small cell lung cancer (SCLC) and nonsmall cell lung cancer (NSCLC) in a high-risk population. METHODS: The serum levels of 4 biomarkers (progastrin-releasing peptide [ProGRP], carcinoembryonic antigen [CEA], squamous cell carcinoma antigen [SCC], and cytokeratin 19 fragment [CYFRA21-1]) were determined in 153 patients with a high risk of lung cancer (12 with a new diagnosis of SCLC, 52 with NSCLC, and 89 without lung cancer). Information about diagnosis delays was collected through interviews of all participants. RESULTS: Significantly higher serum levels of ProGRP (P <.0001) were found among the SCLC patients versus the rest of the population. A receiver operating characteristic curve analysis established the cutoff values of ProGRP, CEA, SCC, and CYFRA21-1 as 300 pg/mL, 7.3 ng/mL, 3 ng/mL, and 6.5 ng/mL, respectively. The sensitivity and specificity of ProGRP in diagnosing SCLC were 75% and 100%, respectively. Among the 14 lung cancer patients with a false-negative computed tomography (CT) result, the diagnostic panel detected 8 additional cancers. CONCLUSIONS: This panel increased the diagnostic specificity for high-risk subjects (those with renal failure being excluded), and auxiliary to a CT scan, it increased the sensitivity for patients with lung cancer. These results might be applied to shorten the diagnosis delay at health care institutions in China. Cancer 2015;121:3113-21. V C 2015 American Cancer Society.KEYWORDS: biomarker, delayed diagnosis, non-small cell lung cancer, progastrin-releasing peptide (ProGRP), small cell lung cancer. INTRODUCTIONCurrently, lung cancer is the most common cancer and the leading cause of cancer-related deaths worldwide. 1 Lung cancer has replaced liver cancer to become the top killer among malignant tumors in China for the past 3 decades, during which the registered mortality rate for lung cancer increased by 465%. 2,3 Among lung cancer deaths, 87% are attributable to cigarette smoking. 4 The mortality rate of lung cancer is approximately 23 times higher for current male smokers and 13 times higher for female smokers versus lifelong nonsmokers. 5 A population-based, cross-sectional study estimated the total number of lung cancer deaths in China to be 493,348 (338,346 males and 155,002 females) in 2008. 6 The variations in lung cancer mortality rates between males and females seen in China and across other countries reflect differences in the stages and degrees of the tobacco epidemic. [7][8][9][10]

Highly Sensitive Marker Panel for Guidance in Lung Cancer Rapid Diagnostic Units

“…Here we provide an improved classification algorithm achieving a superior sensitivity for LC in the context of RDU. In this refined algorithm, besides the smoking status, the routinely used CEA was incorporated, corroborating its diagnostic capacity especially for late-stage tumours4242526. Briefly, our approach involves the measurement of EGF, sCD26, CAL and CEA to generate a classification score for each individual to predict LC.…”

“…Yang et al 24. reported for high-risk patients with no lesions on CT scan a panel, which resulted positive when at least one of the markers CEA, SCC, CYFRA 21.1 and Progastrin-releasing Peptide was altered, yielding a sensitivity of 76.6% and specificity of 94.4%, though they do not report data on another independent sample set.…”

Instability of Plasma and Serum Progastrin-Releasing Peptide During Repeated Freezing and Thawing

“…ProGRP is a putative biomarker for SCLC, a subtype of lung cancer 1, 2, 3, 4. In this study, we assessed the effects of multiple freeze–thaw cycles on the stability of proGRP in plasma and serum.…”

“…Recently, circulating progastrin-releasing peptide (proGRP) has been reported as a putative biomarker of small cell lung carcinoma (SCLC) 1, 2, 3, 4. ProGRP is a precursor of gastrin-releasing peptide (GRP), a gastrointestinal hormone of the bombesin family 5, 6.…”

“…However, proGRP is a stable protein with half-life of 19–28 days [8]. An assay for serum proGRP showed high sensitivity (47–86%) and specificity (95–100%) in diagnosing SCLC 1, 2, 3, 4. Testing for plasma proGRP also exhibited high sensitivity (> 80%) and specificity (> 90%) [9].…”