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Proteomics provides individualized options of precision medicine for patients with gastric cancer
Wenwen Huang1, Dongdong Zhan2,3, Yazhuo Li4
1Department of Gastrointestinal Oncology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Peking University Cancer Hospital and Institute, Beijing, 100142, China.
Abstract:
While precision medicine driven by genome sequencing has revolutionized cancer care, such as lung cancer, its impact on gastric cancer (GC) has been minimal. GC patients are routinely treated with chemotherapy, but only a fraction of them receive the clinical benefit. There is an urgent need to develop biomarkers or algorithms to select chemo-sensitive patients or apply targeted therapy. Here, we carried out retrospective analyses of 1,020 formalin-fixed, paraffin-embedded GC surgical resection samples from 5 hospitals and developed a mass spectrometry-based workflow for proteomic subtyping of GC. We identified two proteomic subtypes: the chemo-sensitive group (CSG) and the chemo-insensitive group (CIG) in the discovery set. The 5-year overall survival of CSG was significantly improved in patients who had received adjuvant chemotherapy after surgery compared with those who received surgery only (64.2% vs. 49.6%; Cox P-value=0.002), whereas no such improvement was observed in CIG (50.0% vs. 58.6%; Cox P-value=0.495). We validated these results in an independent validation set. Further, differential proteome analysis uncovered 9 FDA-approved drugs that may be applicable for targeted therapy of GC. A prospective study is warranted to test these findings for future GC patient care.
Insights
Gastric cancer (GC) proteomic subtyping identified chemo-sensitive and chemo-insensitive groups. Chemo-sensitive patients significantly benefit from adjuvant chemotherapy, guiding personalized gastric cancer treatment.
Area of Science:
- Oncology
- Proteomics
- Cancer Research
Background:
- Precision medicine advances have minimally impacted gastric cancer (GC) care.
- Current chemotherapy benefits only a fraction of GC patients, necessitating better predictive biomarkers.
- Identifying chemo-sensitive patients is crucial for effective gastric cancer treatment.
Purpose of the Study:
- To develop a proteomic subtyping workflow for gastric cancer.
- To identify distinct proteomic subtypes predicting chemotherapy response in GC.
- To discover potential targeted therapies for gastric cancer.
Main Methods:
- Retrospective analysis of 1,020 gastric cancer surgical resection samples.
- Development of a mass spectrometry-based proteomic subtyping workflow.
- Validation of identified subtypes in an independent patient cohort.
Main Results:
- Two proteomic subtypes were identified: chemo-sensitive group (CSG) and chemo-insensitive group (CIG).
- CSG patients showed significantly improved 5-year overall survival with adjuvant chemotherapy versus surgery alone (64.2% vs. 49.6%).
- No survival benefit from chemotherapy was observed in CIG patients (50.0% vs. 58.6%).
- Differential proteome analysis suggested 9 FDA-approved drugs for potential targeted therapy in GC.
Conclusions:
- Proteomic subtyping can effectively distinguish chemo-sensitive from chemo-insensitive gastric cancer patients.
- This subtyping approach can guide the selection of adjuvant chemotherapy for improved patient outcomes.
- The study identified potential targeted therapies, warranting prospective investigation for future GC patient care.
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