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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Colorectal cancer patients | Patients with pathologically confirmed colorectal cancer. Colorectal tumor and adjacent normal tissue specimens will be analyzed for SLC15A3 expression, or serum specimen will be analyzed for histidine-related metabolites, or whole blood samples will be analyzed for peripheral blood immune cell functions. |
| |
| ICB responders | Patients with colorectal cancer who previously received PD-1 immune checkpoint blockade and achieved a clinical response. Tumor tissue will be analyzed for SLC15A3 expression, and serum specimen will be analyzed for histidine-related metabolites. |
| |
| ICB non-responders | Patients with colorectal cancer who previously received PD-1 immune checkpoint blockade and did not achieve a clinical response. Tumor tissue will be analyzed for SLC15A3 expression, and serum specimen will be analyzed for histidine-related metabolites. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Immunohistochemistry or immunofluorescence | Other | Formalin-fixed paraffin-embedded (FFPE) colorectal tumor and adjacent normal tissue specimens will be analyzed for SLC15A3 expression by immunohistochemistry and/or immunofluorescence. |
| Measure | Description | Time Frame |
|---|---|---|
| SLC15A3 expression | SLC15A3 expression measured by immunohistochemistry (IHC) or immunofluorescence in formalin-fixed paraffin-embedded colorectal tumor and adjacent normal tissue specimens. | 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). | Baseline and after 9 weeks (one round of treatment). |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | 5 years. |
| Overall survival |
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Inclusion Criteria:
Exclusion Criteria:
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Patients with pathologically confirmed colorectal cancer who received care at the Department of Gastroenterology, Department of Oncology, or Department of General Surgery at Renji Hospital, Shanghai Jiao Tong University School of Medicine.
| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Wan Du, M.D. | Contact | (86)13788972966 | duwan2017@126.com | |
| Youli Chen | Contact | (86)13656503169 | chenylpetri@gmail.com |
| Name | Affiliation | Role |
|---|---|---|
| Jing-Yuan Fang, M.D. | Division of Gastroenterology and Hepatology, NHC Key Laboratory of Digestive Diseases, Renji Hospital, School of Medicine, Shanghai Jiao Tong University | Principal Investigator |
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| ID | Term |
|---|---|
| D015179 | Colorectal Neoplasms |
| ID | Term |
|---|---|
| D007414 | Intestinal Neoplasms |
| D005770 | Gastrointestinal Neoplasms |
| D004067 | Digestive System Neoplasms |
| D009371 | Neoplasms by Site |
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| ID | Term |
|---|---|
| D007150 | Immunohistochemistry |
| D005455 | Fluorescent Antibody Technique |
| D004797 | Enzyme-Linked Immunosorbent Assay |
| D005434 | Flow Cytometry |
| ID | Term |
|---|---|
| D006651 | Histocytochemistry |
| D003584 | Cytological Techniques |
| D019411 | Clinical Laboratory Techniques |
| D019937 | Diagnostic Techniques and Procedures |
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Whole blood specimen; Serum specimen; Surgical tissue specimen
| Serum metabolomic analysis or ELISA | Other | Serum specimens from patients with colorectal cancer will be analyzed for histidine and related metabolites and selected biomarkers by metabolomics and/or ELISA. |
|
| Flow cytometry | Other | Peripheral blood mononuclear cells (PBMCs) will be separated from whole blood samples and assessed for immune cell phenotype and functional markers by flow cytometry. |
|
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. |
| 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. | Baseline and after 9 weeks (one round of treatment). |
| Percentage of granzyme B-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 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. | 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. | Baseline at initial diagnosis or tissue collection. |
| D009369 | Neoplasms |
| D004066 | Digestive System Diseases |
| D005767 | Gastrointestinal Diseases |
| D003108 | Colonic Diseases |
| D007410 | Intestinal Diseases |
| D012002 | Rectal Diseases |
| D003933 | Diagnosis |
| D006652 | Histological Techniques |
| D008919 | Investigative Techniques |
| D007158 | Immunologic Techniques |
| D007124 | Immunoenzyme Techniques |
| D007118 | Immunoassay |
| D007163 | Immunosorbent Techniques |
| D015336 | Molecular Probe Techniques |
| D002469 | Cell Separation |
| D003592 | Cytophotometry |
| D005470 | Fluorometry |
| D008163 | Luminescent Measurements |
| D010783 | Photometry |
| D002623 | Chemistry Techniques, Analytical |