This observational study aims to investigate the role of histidine and its transporter SLC15A3 in modulating the sensitivity of colorectal cancer to immunotherapy. By analyzing the expression of SLC15A3 in tumor/normal colonic tissues from patients with colorectal cancer and assessing serum histidine metabolic levels, the study seeks to identify potential targets associated with therapeutic resistance and explore possible intervention strategies to improve immune checkpoint blockade treatment efficacy.
Study Type
OBSERVATIONAL
Enrollment
150
Formalin-fixed paraffin-embedded (FFPE) colorectal tumor and adjacent normal tissue specimens will be analyzed for SLC15A3 expression by immunohistochemistry and/or immunofluorescence.
Serum specimens from patients with colorectal cancer will be analyzed for histidine and related metabolites and selected biomarkers by metabolomics and/or ELISA.
Peripheral blood mononuclear cells (PBMCs) will be separated from whole blood samples and assessed for immune cell phenotype and functional markers by flow cytometry.
SLC15A3 expression
SLC15A3 expression measured by immunohistochemistry (IHC) or immunofluorescence in formalin-fixed paraffin-embedded colorectal tumor and adjacent normal tissue specimens.
Time frame: Baseline archival tissue specimen from surgical resection or diagnostic biopsy.
Serum histidine concentration
Serum histidine concentration measured using liquid chromatography-mass spectrometry (LC-MS) in serum samples collected before treatment initiation and, where available, after 9 weeks (one round of treatment).
Time frame: Baseline and after 9 weeks (one round of treatment).
Progression-free survival
Progression-free survival, defined as the time from initial diagnosis or treatment initiation to documented disease progression, recurrence, or death from any cause, whichever occurs first, in patients with colorectal cancer with available follow-up information.
Time frame: 5 years.
Overall survival
Overall survival, defined as the time from initial diagnosis or treatment initiation to death from any cause in patients with colorectal cancer with available follow-up information.
Time frame: 5 years.
Percentage of IFN-gamma-positive T cells
Peripheral blood mononuclear cells (PBMCs) from archived blood samples of patients with colorectal cancer will be assessed by flow cytometry to evaluate the percentage of IFN-gamma-positive T cells as a T cell effector function marker. Samples collected before treatment initiation and, where available, after 9 weeks (one round of treatment) will be analyzed.
Time frame: Baseline and after 9 weeks (one round of treatment).
Percentage of granzyme B-positive T cells
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Peripheral blood mononuclear cells (PBMCs) from archived blood samples of patients with colorectal cancer will be assessed by flow cytometry to evaluate the percentage of granzyme B-positive T cells as a T cell effector function marker. Samples collected before treatment initiation and, where available, after 9 weeks (one round of treatment) will be analyzed.
Time frame: Baseline and after 9 weeks (one round of treatment).
Clinicopathological characteristics
Clinicopathological characteristics of patients with colorectal cancer, including age, sex, tumor location, AJCC TNM stage, and histological grade, extracted from available medical records.
Time frame: Baseline at initial diagnosis or tissue collection.