Mechanism of Gastric Signet Ring Cell Carcinoma Based on Microproteomics

Gastric Cancer Clinical Trial

Official title:

Mechanism of Gastric Signet Ring Cell Carcinoma Based on Microproteomics

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT05985577
• Other study ID #: IRB-2023-584
• Status: Active, not recruiting
• Start date: March 2, 2023
• Est. completion date: July 30, 2024

Study information

• Verified date: August 2023
• Source: Zhejiang Cancer Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational [Patient Registry]

Clinical Trial Summary

Gastric signet ring cell carcinoma (GSRCC) possesses unique epidemiology and pathogenesis in the field of cancer, but its incidence is low. Unfortunately, there is currently a lack of systematic research focusing on the prognostic proteomic features of GSRCC. Given this knowledge gap, this study aims to comprehensively characterize the proteomic landscape of GSRCC using a reliable and reproducible DIA-PCT method. This study objectives include characterizing the heterogeneity of GSRCC, performing molecular typing, identifying potential biomarkers and therapeutic targets, and providing a resource for stratified analysis of GSRCC. To achieve these goals, the investigators selected a cohort of 112 GSRCC patients from a pool of over 10,000 gastric cancer patients and conducted a proteomic analysis using the DIA-PCT method. This meticulous approach revealed four novel proteomic subtypes of GSRCC, each exhibiting unique molecular characteristics. Additionally, the investigators discovered that PRDX2 and DDX27 can serve as predictive biomarkers for GSRCC, which were further validated in an independent cohort of 75 GSRCC patients. Furthermore, the investigators paid particular attention to the MLT-GSRCC subgroup and identified three distinct proteomic clusters among MLT-GSRCC patients. Subtype 2 within this subgroup demonstrated the poorest prognosis. Through a rigorous screening process, the investigators determined potential targets for the treatment of GSRCC. In conclusion, these findings contribute to the investigators understanding of the heterogeneity of GSRCC and provide valuable resources for future clinical stratification and targeted treatment strategies.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 300
• Est. completion date: July 30, 2024
• Est. primary completion date: June 30, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A and older

Eligibility

Inclusion Criteria:

• confirmed GSRCC by pathology, where GSRCC is defined as having a percentage of signet ring cell = 50%

• patients with complete medical information

• patients with survival follow-up information

Exclusion Criteria:

• patients with other malignant tumors

• presence of other pathological components (e.g., neuroendocrine carcinoma and squamous cell carcinoma, etc)

• incomplete or lost case information

Related Conditions & MeSH terms

• Carcinoma
• Gastric Cancer
• Signet Ring Cell Carcinoma

Intervention

Other:
• Without any intervention
There were no special interventions for the two groups.

Locations

Country	Name	City	State
China	Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital)	Hangzhou	Zhejiang

Sponsors (1)

Lead Sponsor	Collaborator
Zhejiang Cancer Hospital

Country where clinical trial is conducted

China, 

References & Publications (5)

Asleh K, Negri GL, Spencer Miko SE, Colborne S, Hughes CS, Wang XQ, Gao D, Gilks CB, Chia SKL, Nielsen TO, Morin GB. Proteomic analysis of archival breast cancer clinical specimens identifies biological subtypes with distinct survival outcomes. Nat Commun — View Citation

Chen J, Liu K, Luo Y, Kang M, Wang J, Chen G, Qi J, Wu W, Wang B, Han Y, Shi L, Wang K, Han X, Ma X, Liu W, Ding Y, Wang L, Liang H, Wang L, Chen J. Single-Cell Profiling of Tumor Immune Microenvironment Reveals Immune Irresponsiveness in Gastric Signet-R — View Citation

Fan Y, Bai B, Liang Y, Ren Y, Liu Y, Zhou F, Lou X, Zi J, Hou G, Chen F, Zhao Q, Liu S. Proteomic Profiling of Gastric Signet Ring Cell Carcinoma Tissues Reveals Characteristic Changes of the Complement Cascade Pathway. Mol Cell Proteomics. 2021;20:100068 — View Citation

Ge S, Xia X, Ding C, Zhen B, Zhou Q, Feng J, Yuan J, Chen R, Li Y, Ge Z, Ji J, Zhang L, Wang J, Li Z, Lai Y, Hu Y, Li Y, Li Y, Gao J, Chen L, Xu J, Zhang C, Jung SY, Choi JM, Jain A, Liu M, Song L, Liu W, Guo G, Gong T, Huang Y, Qiu Y, Huang W, Shi T, Zhu — View Citation

Puccini A, Poorman K, Catalano F, Seeber A, Goldberg RM, Salem ME, Shields AF, Berger MD, Battaglin F, Tokunaga R, Naseem M, Zhang W, Philip PA, Marshall JL, Korn WM, Lenz HJ. Molecular profiling of signet-ring-cell carcinoma (SRCC) from the stomach and c — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The proteome of tissue	The samples diagnosed as GSRCC by pathology were selected as the samples with signet ring cell content > 70% as judged by 2 pathologists of associate chief physician or above and without previous radiotherapy and chemotherapy. Tumor tissues and paired nat were collected from the same patient at the time of tumor resection and stored in formalin-fixed paraffin embedding (FFPE). Liquid chromatography-mass spectrometry (LC-MS) was used to detect the proteomics in the samples. The proteins in the samples were extracted, and the proteomics in the samples was detected by LC-MS. Qualitative and quantitative analysis was performed to detect the types and content of proteins in the samples.	Lc-MS/MS was used to detect the types of proteins in the samples and the relative amounts in the samples compared with Normal adjacent tissue, an average of one month