Protein Biomarker Found for Early-Stage Lung Cancer

The American Cancer Society (ACS) estimate that in 2018, 154,050 people in the USA will have died from lung cancer and the World Health Organization (WHO) suggest that 1.69 million deaths are brought about by lung cancer worldwide.

Most lung cancers are initially diagnosed at an advanced stage, and so the disease is associated with a poor prognosis, being the leading cause of cancer-related death worldwide. The identification of patients at a resectable early stage of cancer is therefore extremely important.

Scientists at the Kitasato University School of Allied Health Sciences (Kanagawa, Japan) obtained frozen fresh lung cancer tissues and kept at 80 °C until use for proteomic analysis. Sera from 271 patients with lung cancer and 100 healthy controls were used as the training set. In addition, a validation set consisting of sera from 100 patients with lung cancer and 38 healthy controls was also studied.

The team developed monoclonal antibodies to validate their studies. They also performed immunoblotting and the immunoreactive bands on the membranes were detected with Immobilon Western Chemiluminescent HRP Substrate and captured with ATTO Cool Saver System. The team also carried out immunohistochemical staining and for reverse-phase protein array (RPPA) the stained slides were scanned on a microarray scanner Genepix 4000B.

Of the monoclonal antibodies generated, one antibody designated as KU-Lu-1, recognized cytoskeleton-associated protein 4 (CKAP4). CKAP4 was detected in lung cancer cells and tissues, and its secretion into the culture supernatant was also confirmed. The serum CKAP4 levels of lung cancer patients were significantly higher than those of healthy controls. Furthermore, the serum CKAP4 levels were also higher in patients with stage I adenocarcinoma or squamous cell carcinoma than in healthy controls. Serum CKAP4 levels may differentiate lung cancer patients from healthy controls, and they may be detected early even in stage I non–small cell lung cancer. Serum CKAP4 levels were also significantly higher in lung cancer patients than in healthy controls in the validation set.

Yuichi Sato, PhD, a professor of Molecular Diagnostic, and senior author of the study, said, “The use of CKAP4 as a biomarker could change current practices regarding the treatment of lung cancer patients, and the diagnostic accuracies may be markedly improved by the combination of CKAP4 and conventional markers.” The study was published on May 8, 2018, in The American Journal of Pathology.

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Kitasato University School of Allied Health Sciences