Folate One-carbon Malnutrition as the Metabostemness Risk Factor of Malignancy Tumor Development of NSCLC Patients

• ClinicalTrials.gov Identifier: NCT03504098
• Recruitment Status: Unknown
• First Posted: April 20, 2018
• Last Update Posted: May 29, 2019
• Sponsor: National Taiwan University Hospital
• Information provided by (Responsible Party): National Taiwan University Hospital

Study Description

Brief Summary:

Non-small cell lung cancer (NSCLC) accounts for more than two-thirds of lung cancer, which is the leading cause of cancer deaths in Taiwan. The overall prognosis of NSCLC is poor with low 5-year survival rates. Recent advances suggest that malignancy NSCLC cancers are the cancer stem cell (CSC) diseases. The stemness potentials of CSC with epithelial-mesenchymal transdifferentiation ensure their invasion and disseminate to metastsis organs. The self-renewal property of CSC mediates intrinsic drug resistance to cytotoxicity therapy and promoted aggressive relapse tumour. Metabolic reprogramming on bioenergetics of malignant cancer cells has been proposed as the key mediator in the stemness CSC development. Malignancy cells uptake glucose for fermented glycolysis to produce lactate which release resulted in acidified microenvironment to trigger the mTOR and sonic hedgehog metabolic stress signaling in supporting CSC stemness potentials. The metabostemness of cancer cells is the new-dimensional hallmark of malignancy tumour, which may serve as the diagnostic markers for the early detection of malignancy cancers. Folate-mediated one carbon metabolism coordinates glucose into amino acid metabolism to tailor the fuel metabolites in supporting macromolecule synthesis and to sustain the bioenergetics requirement. Acting as the metabolic stressor, low folate intake is associated with increased risks of lung cancers. Folate and one-carbon nutrient status of NSCLC patients in Taiwan, however, has not been assessed. The role of low folate metabolic stress (LFMS) in metabostemness marker and metastasis potentials of malignancy NSCLC is unexplored. The causal effect and the working mechanisms by which LFMS promoted NSCLC malignancy remain elusive.

Condition or disease	Intervention/treatment
Lung Cancer, Nonsmall Cell	Behavioral: nutrition consult

Study Design

• Study Type: Observational
• Estimated Enrollment: 300 participants
• Observational Model: Case-Only
• Time Perspective: Prospective
• Official Title: Folate One-carbon Malnutrition as the Metabostemness Risk Factor of Malignancy Tumor Development and the Prognostic Predictor of Non-small Cell Lung Cancer Patients
• Actual Study Start Date: August 1, 2017
• Estimated Primary Completion Date: July 31, 2020
• Estimated Study Completion Date: July 31, 2020

Groups and Cohorts

Group/Cohort	Intervention/treatment
Lung cancer patients tumor; Using to analysis metabolomic markers, one carbon folate nutrition levels in lung cancer patients.
Lung cancer patients blood; Using to analysis folate, B12, homocysteine levels in plasma and RBC. Using to analysis cDNA gene test in buffy coat.	Behavioral: nutrition consult; Post-lung cancer operation diet pattern
Lung cancer patients; Supply nutrition counseling	Behavioral: nutrition consult; Post-lung cancer operation diet pattern

Outcome Measures

Primary Outcome Measures :

1. Assessment of one-carbon nutrient (folate, choline, betaine, Vitamine B12) intake of lung cancer patients [ Time Frame: Past 0.5-1 year ]
   Using semiquantitative food frequency questionnaires

Secondary Outcome Measures :

1. Measure maternal blood biochemistry (folate, choline, betaine, homocysteine, Vitamine B2, Vitamine B6, Vitamine B12, etc.) [ Time Frame: At baseline ]
   Using blood analysis to calculate the levels of one carbon nutrition
2. Assessment of one-carbon nutrient metabolomic markers in lung cancer patient tumor tissue [ Time Frame: 3 years ]
   Using LC/MS or GC/MS to claculate metabolomic markers

Biospecimen Retention:   Samples Without DNA

blood sample 10c.c

lung tumor tissue

non-lung tumor tissue

Eligibility Criteria

• Ages Eligible for Study: 20 Years to 90 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes
• Sampling Method: Probability Sample

Study Population

Patients who was diagnosed as the first time having NSCLC from NTUH. Patients have no chronic disease / other cancer / chemotherapy / radiotherapy. Patients at least 20 years old.

Criteria

Inclusion Criteria:

• Surgeon diagnosed as the first time having non-small cell lung cancer from the surgical clinic of National Taiwan University Hospital

Exclusion Criteria:

• Patients Suffer from major diseases such as heart, liver, kidney, or peripheral arterial disease, or having mental illness
• Diabetes and non-lung cancer patients
• Pregnancy, breast-feeding pregnant women

Contacts and Locations

Contacts

Contact: Jin-Shing Chen; 8862-2312345670918; chenjs@ntu.edu.tw

Contact: Rwei-Fen S.Huang; 8862-29052512; 034825@mail.fju.edu.tw

Locations

Taiwan

National Taiwan University Hospital; Recruiting

Taipei, Taiwan, 100

Contact: Jin-Shing Chen 8862-23123456-70918 chenjs@ntu.edu.tw

Sponsors and Collaborators

National Taiwan University Hospital

Investigators

• Principal Investigator: Chin-Pao Cheng; National Taiwan University Hospital

More Information

• Responsible Party: National Taiwan University Hospital
• ClinicalTrials.gov Identifier: NCT03504098
• Other Study ID Numbers: 201701123RINC
• First Posted: April 20, 2018
• Last Update Posted: May 29, 2019
• Last Verified: May 2019

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by National Taiwan University Hospital:

One-carbon metabolism; Folate; Choline; metabolomic marker; Cancer risk

Additional relevant MeSH terms:

Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Malnutrition; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Nutrition Disorders; Carcinoma, Bronchogenic; Bronchial Neoplasms