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Neoadjuvant Camrelizumab Plus Domestically Developed Paclitaxel Polymeric Micelle and Cisplatin for Locally Advanced ESCC: a Phase Ⅱ Trial with a Plasma Proteomics Predictive Model (POINTS Trial)

ABSTRACT: Plasma proteomic study for neoadjuvant therapy efficacy in locally advanced ESCC: 16 preoperative plasma samples, split into MPR/non-MPR groups (8 each) by postoperative pathology. Processed via MagReSyn® SAX magnetic bead enrichment, SDS/TCEP solubilization and trypsin digestion; analyzed by DIA-MS on Easy-nLC 1200-Orbitrap Astral (MS1:395–1005 m/z; MS2:12 m/z staggered windows). Raw data converted with ProteoWizard, library built in EncyclopeDIA, quantified in Skyline-daily. 310 DEPs identified for treatment response predictive model construction. Data collected under ethical guidelines, all patients provided written informed consent.

ORGANISM(S): Homo Sapiens

SUBMITTER: Lei Fang

PROVIDER: PXD075653 | iProX | Sat Mar 14 00:00:00 GMT 2026

REPOSITORIES: iProX

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Project description:Background: Colorectal cancer is the third most common and the fourth most lethal cancer in the world. In the majority of cases, patients are diagnosed at an advanced stage or even metastatic, thus explaining the high mortality. The standard protocol for treating patients with locally advanced non-metastatic colorectal cancer (CRC) is neoadjuvant radio-chemotherapy (NRCT) with 5-fluorouracil (5-FU), but the resistance rate to this treatment remains high with approximately 30% of non-responders. The lack of evidence available in clinical practice to predict NRCT resistance to 5-FU and to guide clinical practice therefore encourages the search for biomarkers of this resistance. Methods: From twenty-three formalin-fixed paraffin-embedded (FFPE) biopsies performed before NRCT with 5-FU of locally advanced non-metastatic CRC patients, we extracted and analysed the tumor proteome of these patients. From clinical data, we were able to classify the twenty-two patients in our cohort into three treatment response groups: non-responders (NR), partial responders (PR) and total responders (TR), and to compare the proteomes of these different groups. Results: We have highlighted 384 differentially expressed proteins between NR and PR, 248 between NR and TR and 417 between PR and TR. Among these proteins, we have identified many differentially expressed proteins identified as having a role in cancer (IFIT1, FASTKD2, PIP4K2B, ARID1B, SLC25A33: overexpressed in TR; CALD1, CPA3, B3GALT5, CD177, RIPK1: overexpressed in NR). We have also identified that DPYD, the main degradation enzyme of 5-FU, was overexpressed in NR, as well as several ribosomal and mitochondrial proteins also overexpressed in NR. Conclusions: From these retrospective study, we implemented a protein extraction protocol from FFPE biopsy to highlight protein differences between different response groups to RCTN with 5-FU in patients with locally advanced non-metastatic CRC. These results will pave the way for a larger cohort for better sensitivity and specificity of the signature to guide decisions in the choice of treatment.

Dataset Information

Neoadjuvant Camrelizumab Plus Domestically Developed Paclitaxel Polymeric Micelle and Cisplatin for Locally Advanced ESCC: a Phase Ⅱ Trial with a Plasma Proteomics Predictive Model (POINTS Trial)

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