Clinical trial NCT05985577: Mechanism of Gastric Signet Ring Cell Carcinoma Based on Microproteomics
Official title: Mechanism of Gastric Signet Ring Cell Carcinoma Based on Microproteomics
Study type: OBSERVATIONAL
Overall status: ACTIVE_NOT_RECRUITING
Conditions: Gastric Cancer
Signet Ring Cell Carcinoma
Keywords: Gastric signet ring cell carcinoma
Molecular Subtypes
Proteomics
Prognostic markers
Drug target
Lead sponsor: Zhejiang Cancer Hospital
Sponsor class: OTHER
First posted: 2023-08-14
Enrollment: 300
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_ONLY
Time perspective: OTHER
Sampling method: PROBABILITY_SAMPLE
Study population: These cases had a signet ring cell content greater than 70% and had not undergone prior chemotherapy or radiotherapy

Brief 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.


Eligibility criteria: 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

Primary outcomes:
measure: The proteome of tissue
timeFrame: 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
Secondary outcomes:
Other outcomes:
Locations:
city: Hangzhou
country: China
facility: Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital)
state: Zhejiang
Study officials:
References:
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 colon reveals potential new therapeutic targets. Oncogene. 2022 Jun;41(26):3455-3460. doi: 10.1038/s41388-022-02350-6. Epub 2022 May 26.
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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-Ring Cell Carcinoma. Gastroenterology. 2023 Jul;165(1):88-103. doi: 10.1053/j.gastro.2023.03.008. Epub 2023 Mar 14.