Evidence map›Paper›PMID 40890441›Full record

ArticleScientific reports2025

Profiling plasma protease activity with charge-changing peptides enables detection and classification of gastrointestinal cancers.

Thanawat Suwatthanarak, Florian Goncalves, Pariyada Tanjak, Kullanist Thanormjit, Amphun Chaiboonchoe, Onchira Acharayothin, Phattarapon Sonthi, Tharathorn Suwatthanarak, Thammawat Parakonthun, Jirawat Swangsri and 5 more

Abstract read
In one paragraph

Article in Scientific reports, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

15 authors.

Thanawat SuwatthanarakSiriraj Cancer Center, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, 10700, Thailand.
Florian GoncalvesKnight Cancer Institute, Oregon Health & Science University, Portland, OR, 97239, USA.
Pariyada TanjakSiriraj Cancer Center, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, 10700, Thailand.
Kullanist ThanormjitSiriraj Cancer Center, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, 10700, Thailand.
Amphun ChaiboonchoeDepartment of Pharmacology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, 10700, Thailand.
Onchira AcharayothinDepartment of Surgery, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, 10700, Thailand.
Phattarapon SonthiDepartment of Surgery, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, 10700, Thailand.
Tharathorn SuwatthanarakDepartment of Surgery, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, 10700, Thailand.
Thammawat ParakonthunDepartment of Surgery, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, 10700, Thailand.
Jirawat SwangsriDepartment of Surgery, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, 10700, Thailand.
Asada MethasateDepartment of Surgery, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, 10700, Thailand.
Prasert AuewarakulDepartment of Microbiology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, 10700, Thailand.
Melissa H WongKnight Cancer Institute, Oregon Health & Science University, Portland, OR, 97239, USA.
Jared M FischerKnight Cancer Institute, Oregon Health & Science University, Portland, OR, 97239, USA.
Vitoon ChinswangwatanakulSiriraj Cancer Center, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, 10700, Thailand. vitoon.chi@mahidol.ac.th.

Funding

Foundation for Cancer Care, Siriraj Hospital R016641006
6 · The paper itself

Abstract

Early detection of gastrointestinal (GI) cancers-including colorectal cancer (CRC), gastric cancer (GC), and esophagogastric junction cancer (EGJC)-is essential for improving patient outcomes. However, current diagnostic methods such as endoscopy and colonoscopy are invasive, costly, and not widely accessible. Proteases are elevated in many cancers and are detectable in peripheral blood, making them promising candidates for noninvasive diagnostic strategies. We employed a six-probe charge-changing peptide (CCP) panel to profile cancer-associated protease activity in human plasma. Each CCP undergoes a charge shift upon cleavage by a specific protease, enabling detection via gel electrophoresis. Plasma samples from GI cancer patients (CRC, GC, EGJC; N = 68) and healthy controls (HC; N = 31) were analyzed. Protease activity profiles were analyzed using statistical tests, principal component analysis, and binary logistic regression (LR) models trained on the most informative probes. Model performance was evaluated through repeated cross-validation. Distinct protease activity profiles were observed among CRC, upper GI cancers (UGIC; GC + EGJC), and HC groups. Probe designed to be cleaved by cathepsin B showed the strongest discrimination between cancer and control samples, while probes designed to be cleaved by ubiquitin-specific peptidase 15 and plasmin were identified as the most informative subtype-specific markers for UGIC and CRC, respectively. LR models built on these single probes demonstrated excellent diagnostic performance, with AUCs exceeding 0.95, and both sensitivity and specificity greater than 90%. Our findings highlight CCP-based protease profiling as a minimally invasive, accurate, and scalable method for GI cancer detection and classification. This platform holds strong potential for clinical application in cancer screening, pending further validation in larger, independent cohorts.

Indexed as

Biomarkers, TumorGastrointestinal NeoplasmsPeptide HydrolasesPeptidesAgedCase-Control StudiesEarly Detection of CancerFemaleHumansMaleMiddle AgedBiomarkers, TumorPeptide HydrolasesPeptidesColorectal adenocarcinomaEsophagogastric junction adenocarcinomaGastric adenocarcinomaPeptidePlasmaProtease

Identifiers

PMID40890441
PMCPMC12402143

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.