Early Detection of Lung Cancer Possible With Newly Identified Biomarker

Early Detection of Lung Cancer Possible With Newly Identified Biomarker

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Highlights:
  • Novel biomarker (CKAP4) that is detected as early as in stage 1 non-small-cell lung cancer and squamous cell carcinoma now identified.
  • Poor prognosis of lung cancer is mainly due to the late diagnosis of the disease.
  • Using a combination of CKAP4 and conventional markers for early diagnosis could markedly improve diagnostic accuracies and change current practices regarding the treatment of lung cancer patients.
Investigators have found significantly higher levels of cytoskeleton-associated protein 4 (CKAP4) in the blood of patients with lung cancer than in healthy individuals. Moreover, the protein is sensitive enough to be detected in the patients' blood as early as in stage I of non-small-cell lung cancer and squamous cell carcinoma, compared to current biomarkers. This could potentially make it a non-invasive diagnostic marker for specific lung cancers to be used for early detection and to improve patient outcomes.
Early Detection of Lung Cancer Possible With Newly Identified Biomarker

"The identification of patients at an early stage of cancer when it can be treated surgically is extremely important to improve prognosis," explained Yuichi Sato, PhD, Department of Molecular Diagnostics, Kitasato University School of Allied Health Sciences, Sagamihara, Kanagawa, Japan, who led the study. "We need better biomarkers for early diagnosis."

The findings are published in The American Journal of Pathology

Cytoskeleton-associated protein 4 (CKAP4) or CLIMP-63 (cytoskeleton-linking membrane protein 63)

CKAP4, apart from playing an essential role in the maintenance of the endoplasmic reticulum structure has more recently been identified as a cell surface receptor for four unique extracellular ligands (substances that bind to biomolecules to serve a biological function); these are tissue plasminogen activator, surfactant protein A, Dickkopf1 (DKK1), and antiproliferative factor.

CKAP4 has also been described as a marker in different cancers. Recently, simultaneous expressions of DKK1 and CKAP4 were frequently observed in tumor lesions of human pancreatic and lung cancers, and it was noted that if the levels of the co-expressed proteins in tumor tissues were less, then there was better prognosis and relapse-free survival in the patients.

Current Biomarkers for Lung Cancer

The biomarkers used in detecting lung cancer up until now are not sensitive enough to detect tumors at an early stage; these include carcinoma embryonic antigen (CEA), sialyl Lewis X antigen (SLX), squamous cell carcinoma (SCC) antigen, and cytokeratin fragment (CYFRA) 21-1. Across various stages of the disease (I-IV), the sensitivities of serum CEA, CYFRA, and SCCA are reported as 30 to 52, 17 to 82, and 24 to 39 percent, respectively. Sensitivity denotes the fraction of people who have the disease and who test positive. A perfect diagnostic marker will show 100% sensitivity, i.e., all patients with the disease will be detected.

Study - Detection of high levels of CKAP4 in lung cancer patients

  • Two hundred and seventy one lung cancer patients and hundred healthy individuals were chosen for the study.
  • Blood taken from the individuals were analyzed using a reverse-phase protein array (RPPA) analysis machine that measures protein expression levels in a large number of biological samples using validated high-quality antibodies.
  • For this particular experiment, the monoclonal antibody used was called KU-Lu-1 which reacted only with tumor cells and tumor stromal fibroblasts and not with normal lung tissues. The crosstalk between stromal cells and cancer cells is highly responsible for the progression of tumors and their metastasis.
  • The researchers confirmed that the KU-Lu-1 antibody recognized CKAP4 in lung cancer cells and tissues using immunoprecipitation and mass spectrometry.
  • The investigators also studied a validation set that consisted of samples from 100 patients with lung cancer and 38 healthy controls.

Results of the study

  • Serum CKAP4 had a sensitivity of 81 percent in the training set and 69 percent in the validation set; these rates were higher than those of the current sero-diagnostic markers.
  • The sensitivity of serum CKAP4 was high even when measured in stage I non-small-cell lung cancer and squamous cell carcinoma.
"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," concluded Dr. Sato.

Lung Cancer

Lung cancer is one of the most common cancers in the world and one that leads to the most number of cancer deaths. Cigarette smoking is the greatest risk factor for lung cancer, followed by pollution, radiation and asbestos exposure.

Common symptoms are a persistent cough that progressively worsens over time, constant chest pain, coughing up blood, shortness of breath and repeated pneumonia or bronchitis problems.

Diagnosing lung cancer at an advanced stage is the main reason for the poor outcome of the disease.

References:
  1. Lung Cancer - (https://medlineplus.gov/lungcancer.html)
  2. Kengo Yanagita, Ryo Nagashio, Shi-Xu Jiang, Yuki Kuchitsu, Kazuo Hachimura, Masaaki Ichinoe, Satoshi Igawa, Eriko Fukuda, Naoki Goshima, Yukitoshi Satoh, Yoshiki Murakumo, Makoto Saegusa, Yuichi Sato. "Cytoskeleton-Associated Protein 4 Is a Novel Serodiagnostic Marker for Lung Cancer", American Journal of Pathology (2018) https://doi.org/10.1016/j.ajpath.2018.03.007

Source-Medindia

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