Evaluation of serum autoantibodies against tumor-associated antigens as biomarkers in lung cancer

Introduction

Although the incidence of lung cancer has slightly declined in recent years, it remains the leading cause of cancer death in the United States because of its aggressive and heterogeneous nature.¹ During the past few decades, results from two major lung cancer cohort studies showed that chest X-ray was not an effective test in lung cancer screening (Shizuoka cohort study, the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial).^2,3 The National Cancer Institute (NCI)-sponsored, National Lung Screening Trial (NLST) found that low-dose chest computed tomography (LDCT) screening could reduce lung cancer–specific mortality in high-risk subjects. However, LDCT showed not to be an ideal screening tool in average risk population due to high false positivity, cost, and radiation exposure.³ Late-stage lung cancers are typically larger in size or/and have lymph node infiltration or have distant metastasis. Cells from higher grade of lung cancer are less differentiated, and they tend to grow quickly and are more likely to spread. Treatment options are greatly influenced by lung cancer stage and grade.

Many studies have shown that certain cellular proteins from cancer tissues can be shed into humoral system and trigger the immune system to generate autoantibodies long before the patients get diagnosed.^4–7 The cellular proteins which can induce immune responses vary greatly in types, including tumor-suppressor gene proteins such as p53⁸ and p16,^9,10 messenger RNA (mRNA) binding proteins such as IGF2BP2/p62,^5,11 cell-cycle regulatory proteins such as Cyclin B1,^6,7 apoptosis inhibitor protein such as Survivin,^12,13 and other cancer-related proteins. Although the mechanism underlying is not completely understood, researchers have been interested in the utilization of autoantibodies as serological markers for cancer diagnosis.^14–21

Studies from our group as well as other groups have demonstrated that autoantibodies against these tumor-associated antigens (TAAs) can be used as biomarkers in cancer detection.^6,22–31 Early in 1995, Lubin et al.⁶ have indicated that sera p53 antibodies could be used as p53 alteration marker before clinical presence of lung cancer. After that, antinuclear antibodies were found in sera from lung cancer patients and the authors suggested that such markers might lead to the discovery of diagnostic and prognostic markers due to the autoimmune feature of lung cancer.²² However, the diagnostic...