Methylated DNA Detect in Paraneoplastic Syndrome of Nervous System

A Research of Value of Free Methylated DNA Detect in Lung Cancer on the Diagnosis and Treatment of Paraneoplastic Syndrome of Nervous System

The purpose of this study is to verify whether the cell-free DNA of lung cancer in the blood can be used as a biomarker for early diagnosis and prognosis evaluation of patient with paraneoplastic syndrome of the nervous system.

Study Overview

• Status: Completed
• Conditions: Paraneoplastic Neurological Syndrome
• Intervention / Treatment: Other: Lung cancer; Other: Positive methylated DNA; Other: Suspected lung cancer

Detailed Description

Paraneoplastic neurological syndrome (PNS) is a clinical syndrome that affects the central nervous system, peripheral nerves, neuromuscular junctions and muscles by the distant influence of the tumor. No tumor cells are visible in the neuropathy. The disease is a rare clinical syndrome, and lung cancer is the most common type of tumor that causes PNS.If PNS can be diagnosed when there are no tumor symptoms, not only can the cause of PNS be identified, but early tumors can be found for treatment time, and measures can be taken in the early stages of the tumor to improve survival. Tumor free DNA (cell-free DNA, cfDNA) methylation detection is to determine the cancer condition and cancer type of the subject by detecting the methylation of free DNA released by tumor cells. In normal cells, tumor suppressor genes are expressed and proto-oncogenes are silenced; in tumor cells, tumor suppressor genes are hypermethylated and silenced, and oncogenes are hypomethylated and activated. The release of free DNA into the blood will be quickly cleared in tens of minutes to several hours, which can reflect the body's cell damage in real time, and is of great significance for monitoring the early occurrence and development of the disease. At present, the sensitivity of lung cancer cf-DNA detection technology is close to 100%, and the specificity is 94%, which is an effective detection technology for early detection of lung cancer.

• Study Type: Observational
• Enrollment (Actual): 40

Contacts and Locations

Study Locations

• China
  • Beijing, China
    • Peking University Third Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 71 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

We recruited consecutive patients with paraneoplastic syndrome.

Description

Inclusion Criteria:

• The agnogenic typical neurological syndromes (including encephalomyelitis, marginal encephalitis, subacute cerebellar degeneration, strabismus ocular clonic-myoclonus, subacute sensory neuron disease, Lambert-Eaton myasthenic syndrome, skin Myositis, etc.) patient who predisposed to a tumor.
• Pathologically confirmed as lung cancer or suggested as lung cancer patient by imaging (pulmonary CT/Positron Emission Tomography-CT), tumor biomarkers, anti-brain tissue antibodies, etc.

Exclusion Criteria:

• Lacunar infarction
• Aortic atherosclerotic cerebral infarction
• Clear cardiogenic cerebral infarction
• Other related system diseases (arteritis, vascular dissection, migraine and vasospasm, etc.)

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

4

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Lung cancer with positive methylated DNA; Blood DNA methylation abnormalities are found in lung cancer.	Other: Lung cancer; Paraneoplastic neurological syndrome (PNS) is a clinical syndrome that affects the central nervous system, peripheral nerves, neuromuscular junctions and muscles by the distant influence of the tumor. No tumor cells are visible at the neuropathy site.; Other: Positive methylated DNA; Tumor-free DNA (cfDNA) methylation detection is to determine the cancer condition and cancer type of the subject by detecting the methylation of free DNA released by tumor cells.
Lung cancer with negative methylated DNA; Blood DNA methylation abnormalities are not found in lung cancer.	Other: Lung cancer; Paraneoplastic neurological syndrome (PNS) is a clinical syndrome that affects the central nervous system, peripheral nerves, neuromuscular junctions and muscles by the distant influence of the tumor. No tumor cells are visible at the neuropathy site.
Suspected lung cancer with positive methylated DNA; Blood DNA methylation abnormalities are found in suspected lung cancer.	Other: Positive methylated DNA; Tumor-free DNA (cfDNA) methylation detection is to determine the cancer condition and cancer type of the subject by detecting the methylation of free DNA released by tumor cells.; Other: Suspected lung cancer; Paraneoplastic neurological syndrome (PNS) is a clinical syndrome that affects the central nervous system, peripheral nerves, neuromuscular junctions and muscles by the distant influence of the tumor. No tumor cells are visible at the neuropathy site.
Suspected lung cancer with negative methylated DNA; Blood DNA methylation abnormalities are not found in suspected lung cancer.	Other: Suspected lung cancer; Paraneoplastic neurological syndrome (PNS) is a clinical syndrome that affects the central nervous system, peripheral nerves, neuromuscular junctions and muscles by the distant influence of the tumor. No tumor cells are visible at the neuropathy site.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Level of cf-DNA	Tumor-free DNA (cfDNA) methylation detection is to determine the cancer condition and cancer type of the subject by detecting the methylation of free DNA released by tumor cells.	1 year after recruitment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes of mRS score	Documentation in the medical record of a Modified Rankin Score (mRS). The Modified Rankin Score (mRS) is a 6 point disability scale with possible scores ranging from 0 to 5. A separate category of 6 is usually added for patients who expire. The Modified Rankin Score (mRS) is the most widely used outcome measure in stroke clinical trials. Standardized interviews to obtain a mRS score are recommended at 3 months (90 days) following hospital discharge.	1 year after recruitment
Survival time	The time interval from disease diagnosis to death	1 years after recruitment
1-year mortality rate	The rate of death among all the inclusion patients after 1 year	1 year after recruitment
Incidence of lung cancer	The rate of lung cancer occurence among all the inclusion patients	1 year after recruitment

Collaborators and Investigators

• Sponsor: Peking University Third Hospital

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2017
• Primary Completion (Actual): July 1, 2019
• Study Completion (Actual): July 1, 2019

Study Registration Dates

• First Submitted: June 29, 2020
• First Submitted That Met QC Criteria: June 29, 2020
• First Posted (Actual): July 2, 2020

Study Record Updates

• Last Update Posted (Actual): July 7, 2020
• Last Update Submitted That Met QC Criteria: July 1, 2020
• Last Verified: July 1, 2020

More Information

Terms related to this study

• Keywords: Paraneoplastic neurological syndrome; Cell-free DNA
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Disease; Syndrome; Paraneoplastic Syndromes
• Other Study ID Numbers: PUTH2017351

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No