Reduced expression of alanyl aminopeptidase is a robust biomarker of non-familial adenomatous polyposis and non-hereditary nonpolyposis colorectal cancer syndrome early-onset colorectal cancer.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:36748835", "kind": "science-record", "revision": 2, "content_hash": "sha256:dc41f001979bc06f15df11e3be652fba8635171ac91341d8a383143e3593a4af", "created_at": "2026-11-01T19:01:19Z", "updated_at": "2026-11-01T21:30:04Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Reduced expression of alanyl aminopeptidase is a robust biomarker of non-familial adenomatous polyposis and non-hereditary nonpolyposis colorectal cancer syndrome early-onset colorectal cancer.", "doi": "10.1002/cam4.5675", "pmid": "36748835", "authors": ["Ye Jin Ha", "Yun Jae Shin", "Ka Hee Tak", "Jong Lyul Park", "Jeong Hwan Kim", "Jong Lyul Lee", "Yong Sik Yoon", "Chan Wook Kim", "Seon Young Kim", "Jin Cheon Kim"], "journal": "Cancer medicine", "year": 2023, "abstract": "BACKGROUND: Early-onset colorectal cancer (EOCRC) has been increasing in incidence worldwide but its genomic pathogenesis is mostly undetermined. This study aimed to identify robust EOCRC-specific gene expression patterns in non-familial adenomatous polyposis (FAP) and non-hereditary nonpolyposis colorectal cancer syndrome (HNPCC) EOCRC.\nMETHOD: We first performed gene expression profiling analysis using RNA sequencing of discovery cohort comprised of 49 EOCRC (age <50) and 50 late-onset colorectal cancer (LOCRC) (age >70) specimens. To obtain robust gene expression data from this analysis, we validated differentially expressed genes (DEGs) through TCGA cohort (EOCRC:59 samples, LOCRC:229 samples) and our validation cohort (EOCRC:72 samples, LOCRC:43 samples) using real-time RT-PCR. After the validation of DEGs, we validated the selected gene at protein levels using Western blotting. To identify whether genomic methylation regulates the expression of a particular gene, we selected methylation sites using The Cancer Genome Atlas (TCGA) datasets and validated them by pyrosequencing in our validation cohort.\nRESULTS: The EOCRC patients included in this study had significantly more prominent family history of cancer than the LOCRC patients (23 [46.9%] vs. 13 [26%], p = 0.050). Alanyl aminopeptidase (ANPEP) was significantly downregulated in the EOCRC tissues (FC = 1.78, p = 0.0007) and was also commonly downregulated in the TCGA cohort (FC = -1.08, p = 0.0021). Moreover, the ANPEP mRNA and protein expression levels were significantly downregulated in the EOCRC tissues of our validation cohort (p = 0.037 and 0.027). In comparisons of the normal and tumor tissues in public datasets, the ANPEP level was significantly lower in the tumor tissue in the TCGA dataset (p < 2.2 × 10-16 ) and GSE196006 dataset (p = 0.0005). Furthermore, the ANPEP expression level did not show a decreasing tendency at a young age in the normal colon tissue of the GTEx dataset. Lastly, the hypermethylation of cg26222247 in ANPEP was identified to be weakly associated with reduced ANPEP expression in our EOCRC cohort.\nCONCLUSION: The reduced expression of ANPEP was identified as a novel biomarker of non-FAP and non-HNPCC EOCRC.", "claims": [{"id": "claim-method", "statement": "The survival status was analyzed in each group using the Kaplan–Meier method and compared by the log‐rank test.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:36748835", "locator": "sections[10] \"Survival analysis\" paragraph 2", "quote": "The survival status was analyzed in each group using the Kaplan–Meier method and compared by the log‐rank test."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The data sets used in this study are available from NCBI's Gene Expression Omnibus (GEO) (Accession ID: GSE213092) and Korean Nucleotide Archive (KoNA) (Accession ID: PRJKA220461) (https://www.kobic.re.kr/kona/).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:36748835", "locator": "sections[34] \"DATA AVAILABILITY STATEMENT\" paragraph 2", "quote": "The data sets used in this study are available from NCBI's Gene Expression Omnibus (GEO) (Accession ID: GSE213092) and Korean Nucleotide Archive (KoNA) (Accession ID: PRJKA220461) (https://www.kobic.re.kr/kona/)."}], "state": "complete"}, {"id": "claim-target-result", "statement": "Lower ANPEP expression showed a tendency toward reduced survival in CRC patients.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:36748835", "locator": "sections[20] \"Survival curves\" paragraph 2", "quote": "Both the TCGA‐COAD and TCGA‐READ exhibited that the group having a lower expression of ANPEP showed the tendency of a reduced survival rate in CRC patients (Figure S3A,B). The p‐value determined by log‐rank test in the survival analysis was 0.056 in TCGA‐COAD (Figure S3A) and 0.05 in TCGA‐READ (Figure S3B)."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "partial", "objective": "Lower ANPEP expression showed a tendency toward reduced survival in CRC patients.", "steps": [{"id": "read_published_estimate", "order": 1, "name": "Read the published estimate from the source", "kind": "other", "state": "complete", "blocked_on": null, "description": "The claim, method and evidence span published with the source article.", "duration_hours": null, "parameters": {}, "inputs": ["source:pmid:36748835"], "outputs": ["the published estimate and its evidence"], "instruments": [], "reagents": []}, {"id": "obtain_source_data", "order": 2, "name": "Obtain the source data from the named repository", "kind": "data-preparation", "state": "blocked", "blocked_on": "data:accession_absent", "description": "The GEO series accession resolves and its sample accessions are listed. 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