Short summary

Lung cancer is the leading cause of cancer deaths in Denmark, and this disease is often diagnosed at a late stage. The golden standard for diagnosis is a tumor biopsy, which requires invasive procedures with risk of pneumothorax, bleeding and infection. If a less invasive procedure such as bronchial wash or even just a blood sample could aid in the diagnosis of lung cancer, we could spare the patients some of the invasive procedures.

Rationale

Lung cancer is the leading cause of cancer deaths in Denmark, Europe and globally, partly because lung cancer is often diagnosed in an advanced stage when curative treatment is not possible. When a lesion is detected on a CT scan the patient undergoes diagnostic procedures such as PET scan, bronchoscopy, and biopsy.

Aberrant methylation occurs in almost all tumors, and analysis of methylated circulating tumor specific DNA (ctDNA) has gained increasing interest. A number of studies have suggested its potential for early diagnosis and screening. The primary focus has been on methylated ctDNA as a diagnostic adjunct in manifest lung cancer.

We have developed a methylation analysis of the Homeobox A9 (HOXA9) gene, which serves as an important factor in cell proliferation. Our studies have clearly indicated that methylated HOXA9 DNA is an important prognostic marker in locally advanced lung cancer. Our pilot study showed that methylated HOXA9 in bronchial wash fluid (BWF) could detect lung cancer with a sensitivity, specificity, and positive predictive value of 72.3%, 82.1%, and 86.0%, respectively. Furthermore, a recent study has demonstrated that four simple proteins in serum can predict the presence of lung cancer with a sensitivity of 63%. Therefore, it may be applied as an additional diagnostic tool.

Description of the cohort

Participants are patients undergoing diagnostic workup on suspicion of lung cancer. They are enrolled at the centres diagnosing lung cancer in Denmark.

Data and biological material

Blood samples, bronchial lavage samples, questionnaire, data from the patient record.

Collaborating researchers and departments

Department of Oncology, Vejle Hospital

• Sara Witting Christensen Wen
• Torben Frøstrup Hansen

Department of Pulmonary Medicine, Odense University Hospital

• Amanda Dandanell Juul
• Christian Borbjerg Laursen

Department of Pulmonary Medicine, Aarhus University Hospital

• Torben Riis Rasmussen