Colorectal Cancer
Conditions
Keywords
Colorectal cancer, Histidine, immune checkpoint blockade
Brief summary
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.
Interventions
OTHERImmunohistochemistry or immunofluorescence
Formalin-fixed paraffin-embedded (FFPE) colorectal tumor and adjacent normal tissue specimens will be analyzed for SLC15A3 expression by immunohistochemistry and/or immunofluorescence.
OTHERSerum metabolomic analysis or ELISA
Serum specimens from patients with colorectal cancer will be analyzed for histidine and related metabolites and selected biomarkers by metabolomics and/or ELISA.
OTHERFlow cytometry
Peripheral blood mononuclear cells (PBMCs) will be separated from whole blood samples and assessed for immune cell phenotype and functional markers by flow cytometry.
Sponsors
Jing-yuan Fang, MD, Ph. D
Study design
Observational model
CASE_CONTROL
Time perspective
RETROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Participants aged ≥18 years and ≤100 years. 2. Patients pathologically diagnosed with colorectal cancer based on colonoscopy or surgical specimens and biopsy examination; or patients who previously received PD-1 monoclonal antibody immunotherapy for colorectal cancer.
Exclusion criteria
1. Age \<18 years. 2. Presence of poorly controlled metabolic diseases, including hypertension, diabetes mellitus, hyperlipidemia, hyperuricemia, or hyperthyroidism. 3. Presence of other severe gastrointestinal diseases, including inflammatory bowel disease, ischemic bowel disease, familial adenomatous polyposis, liver cirrhosis, MUTYH-associated polyposis (MAP), Lynch syndrome (LS), or Peutz-Jeghers syndrome (PJS). 4. History of other malignant tumors, or pathological diagnosis of colorectal inflammatory polyps, hyperplastic polyps, neuroendocrine tumors, neuroendocrine carcinoma, or mixed neuroendocrine-non-neuroendocrine neoplasms. 5. History of neurological or psychiatric disorders, such as epilepsy or depression. 6. Unqualified specimens, including hemolyzed serum samples or tissue samples that were not properly preserved in time.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| SLC15A3 expression | Baseline archival tissue specimen from surgical resection or diagnostic biopsy. | SLC15A3 expression measured by immunohistochemistry (IHC) or immunofluorescence in formalin-fixed paraffin-embedded colorectal tumor and adjacent normal tissue specimens. |
| Serum histidine concentration | Baseline and after 9 weeks (one round of treatment). | 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). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression-free survival | 5 years. | 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. |
| Overall survival | 5 years. | 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. |
| Percentage of IFN-gamma-positive T cells | Baseline and after 9 weeks (one round of treatment). | 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. |
| Percentage of granzyme B-positive T cells | Baseline and after 9 weeks (one round of treatment). | 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. |
| Clinicopathological characteristics | Baseline at initial diagnosis or tissue collection. | Clinicopathological characteristics of patients with colorectal cancer, including age, sex, tumor location, AJCC TNM stage, and histological grade, extracted from available medical records. |
Contacts
CONTACTWan Du, M.D.
CONTACTYouli Chen
PRINCIPAL_INVESTIGATORJing-Yuan Fang, M.D.
Division of Gastroenterology and Hepatology, NHC Key Laboratory of Digestive Diseases, Renji Hospital, School of Medicine, Shanghai Jiao Tong University
Outcome results
None listed