Detection and Quantification of Tp53 and p53-Anti-p53 Autoantibody Immune Complex: Promising Biomarkers in Early Stage Lung Cancer Diagnosis.

Keum-Soo Song,Satish Balasaheb Nimse,Taisun Kim,Hey-Jin Kim,Shrikant Dashrath Warkad,Jung-Hoon Kim

doi:10.3390/bios12020127

Keum-Soo Song, Satish Balasaheb Nimse + Show 4 more

Open Access

https://doi.org/10.3390/bios12020127

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Abstract

Lung cancer is a leading cause of death worldwide, claiming nearly 1.80 million lives in 2020. Screening with low-dose computed tomography (LDCT) reduces lung cancer mortality by about 20% compared to standard chest X-rays among current or heavy smokers. However, several reports indicate that LDCT has a high false-positive rate. In this regard, methods based on biomarker detection offer excellent potential for developing noninvasive cancer diagnostic tests to complement LDCT for detecting stage 0∼IV lung cancers. Herein, we have developed a method for detecting and quantifying a p53-anti-p53 autoantibody complex and the total p53 antigen (wild and mutant). The LOD for detecting Tp53 and PIC were 7.41 pg/mL and 5.74 pg/mL, respectively. The detection ranges for both biomarkers were 0–7500 pg/mL. The known interfering agents in immunoassays such as biotin, bilirubin, intra-lipid, and hemoglobin did not detect Tp53 and PIC, even at levels that were several folds higher levels than their normal levels. Furthermore, the present study provides a unique report on this preliminary investigation using the PIC/Tp53 ratio to detect stage I–IV lung cancers. The presented method detects lung cancers with 81.6% sensitivity and 93.3% specificity. These results indicate that the presented method has high applicability for the identification of lung cancer patients from the healthy population.

Highlights

Lung cancer is a leading cause of death worldwide, claiming nearly 1.80 million lives in 2020 [1]
The present study provides a unique report on the preliminary investigation on the use of the p53-Autoantibody immune complex (PIC)/total p53 (Tp53) ratio to detect stage I–IV lung cancers
The linearity regression coefficients were in the range of 0.990–0.995. These results indicate that the presence of biotin, bilirubin, lipid, and hemoglobin, even at levels that are several folds higher than their normal levels, do not interfere with Tp53 and PIC detection

Summary

Introduction

Lung cancer is a leading cause of death worldwide, claiming nearly 1.80 million lives in 2020 [1]. The overall 5-year relative survival rate for lung cancer is 21% [2,3]. If diagnosed at a localized stage, the 5-year survival rate is 59%. Only 17% of lung cancers are diagnosed at a localized stage [4]. Screening with low-dose computed tomography (LDCT) reduced lung cancer mortality by about 20% compared to standard chest X-rays among current or heavy smokers [5]. The American Cancer Society recommends annual LDCT-based lung cancer screening in apparently healthy patients (aged 55 to 80 years) who have at least a 30 pack-year smoking history, current smokers, and those who have quit smoking within the past 15 years [6]. Several reports indicate that LDCT has a high false-positive rate [7]. About 25% of subjects are classified as being positive for lung cancer after three rounds of LDCT screening

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