Academic Journal
Integrated single-cell analysis characterizes malignant epithelial programs and context-dependent immune associations of MP7/SERINC2 in colorectal cancer.
| Τίτλος: | Integrated single-cell analysis characterizes malignant epithelial programs and context-dependent immune associations of MP7/SERINC2 in colorectal cancer. |
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| Συγγραφείς: | Ying W; Department of Radiotherapy, Sichuan Clinical Research Center for Cancer, Sichuan Cancer Hospital and Institute, Sichuan Cancer Center, University of Electronic Science and Technology of China, Chengdu, China., Zhang Y; Department of Gastric Surgery, Sichuan Clinical Research Center for Cancer, Sichuan Cancer Hospital and Institute, Sichuan Cancer Center, University of Electronic Science and Technology of China, Chengdu, China., Wu S; Department of Medical Oncology, Sichuan Clinical Research Center for Cancer, Sichuan Cancer Hospital and Institute, Sichuan Cancer Center, Affiliated Cancer Hospital of University of Electronic Science and Technology of China, Chengdu, China., Wu R; Department of Medical Oncology, Sichuan Clinical Research Center for Cancer, Sichuan Cancer Hospital and Institute, Sichuan Cancer Center, Affiliated Cancer Hospital of University of Electronic Science and Technology of China, Chengdu, China., Li X; Department of Radiotherapy, Sichuan Clinical Research Center for Cancer, Sichuan Cancer Hospital and Institute, Sichuan Cancer Center, University of Electronic Science and Technology of China, Chengdu, China. |
| Πηγή: | Frontiers in immunology [Front Immunol] 2026 Sep 03; Vol. 17, pp. 1918381. Date of Electronic Publication: 2026 Sep 03 (Print Publication: 2026). |
| Τύπος έκδοσης: | Journal Article |
| Γλώσσα: | English |
| Στοιχεία περιοδικού: | Publisher: Frontiers Research Foundation] Country of Publication: Switzerland NLM ID: 101560960 Publication Model: eCollection Cited Medium: Internet ISSN: 1664-3224 (Electronic) Linking ISSN: 16643224 NLM ISO Abbreviation: Front Immunol Subsets: MEDLINE |
| Imprint Name(s): | Original Publication: [Lausanne : Frontiers Research Foundation] |
| Ιατρικοί όροι (MeSH): | Colorectal Neoplasms*/immunology , Colorectal Neoplasms*/genetics , Colorectal Neoplasms*/pathology , Colorectal Neoplasms*/metabolism , Single-Cell Analysis*/methods , Membrane Proteins*/genetics , Membrane Proteins*/metabolism , Epithelial Cells*/metabolism , Epithelial Cells*/pathology , Epithelial Cells*/immunology, Biomarkers, Tumor/genetics ; Humans ; Gene Expression Regulation, Neoplastic ; Cell Line, Tumor ; Single-Cell Gene Expression Analysis ; Transcriptome ; Female |
| Περίληψη: | Introduction: Colorectal cancer (CRC) comprises heterogeneous malignant epithelial states, but it remains unclear which transcriptional programs recur across patients and how these programs relate to the immune context. Methods: We integrated five public single-cell RNA-sequencing datasets comprising 425,402 cells from 119 patients using scVI, defined malignant epithelial cells with inferCNV, and characterized their states and transcriptional programs using cNMF, pySCENIC, and CytoTRACE2. Program recurrence was assessed by rerunning cNMF separately for individual patients. Metaprogram associations were subsequently evaluated in bulk cohorts, CRC cell lines, spatial transcriptomic datasets, and an immune-checkpoint inhibitor (ICI) cohort. Results: We identified five malignant epithelial states and eight metaprograms. MP7, a secretory/goblet-lineage program, was independently recovered in 9 of 26 evaluable patients across three datasets, with reciprocal-best matches in five. Although its top-100 gene profile closely resembled that of normal goblet cells (Spearman r = 0.834), 92.2-94.2% of MP7-dominant cells were retained as malignant under stricter classification criteria. Bulk MP7 scores were sensitive to epithelial composition, and an exploratory 17-gene survival score derived from MP7 showed limited discrimination in nested cross-validation and external cohorts. SERINC2 was prioritized from this gene set for functional testing. SERINC2-targeting shRNAs increased wound closure and Transwell invasion in SW480 and RKO cells, with RNA-level knockdown confirmed in SW480 cells. MP7 and SERINC2 showed context-dependent associations with immune features at the patient and spatial levels, but neither distinguished response in the examined ICI cohort. Discussion: MP7 represents a secretory/goblet-lineage program that recurs in a subset of CRC tumors rather than a broadly shared malignant state. The findings also identify SERINC2 as a candidate regulator of CRC cell motility and invasion, although its mechanism and clinical relevance require further validation. (Copyright © 2026 Ying, Zhang, Wu, Wu and Li.) |
| Competing Interests: | The author(s) declared that this work was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. |
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| Contributed Indexing: | Keywords: SERINC2; colorectal cancer; immune checkpoint blockade; malignant epithelial cells; metaprogram; single-cell RNA sequencing; tumor immune microenvironment |
| Substance Nomenclature: | 0 (Membrane Proteins) 0 (Biomarkers, Tumor) |
| Entry Date(s): | Date Created: 20260918 Date Completed: 20260918 Latest Revision: 20260919 |
| Update Code: | 20260919 |
| PubMed Central ID: | PMC13582626 |
| DOI: | 10.3389/fimmu.2026.1918381 |
| PMID: | 42756464 |
| Βάση Δεδομένων: | MEDLINE |
| ISSN: | 1664-3224 |
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| DOI: | 10.3389/fimmu.2026.1918381 |