Clinical trial NCT03504098: Folate One-carbon Malnutrition as the Metabostemness Risk Factor of Malignancy Tumor Development of NSCLC Patients
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
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Lung Cancer, Nonsmall Cell
Keywords: One-carbon metabolism
Folate
Choline
metabolomic marker
Cancer risk
Lead sponsor: National Taiwan University Hospital
Sponsor class: OTHER
First posted: 2018-04-20
Enrollment: 300
Sex: ALL
Minimum age (years): 20
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: CASE_ONLY
Time perspective: PROSPECTIVE
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.

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.


Eligibility 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

Primary outcomes:
measure: Assessment of one-carbon nutrient (folate, choline, betaine, Vitamine B12) intake of lung cancer patients
timeFrame: Past 0.5-1 year
Secondary outcomes:
measure: Measure maternal blood biochemistry (folate, choline, betaine, homocysteine, Vitamine B2, Vitamine B6, Vitamine B12, etc.)
timeFrame: At baseline
measure: Assessment of one-carbon nutrient metabolomic markers in lung cancer patient tumor tissue
timeFrame: 3 years
Other outcomes:
Locations:
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital
Study officials:
affiliation: National Taiwan University Hospital
name: Chin-Pao Cheng
role: PRINCIPAL_INVESTIGATOR
References: