Abstract 1413
Background
Although recent advances in high-throughput technology have provided many insights into gastric cancer (GC), few reliable biomarkers for handling diffuse type GC are identified. Here, we aim to identify a prognostic and predictive signature predicting heterogeneous clinical courses of diffuse type GC.
Methods
We analysed RNA-seq based transcriptome data to identify a molecular signature in 150 gastric tissue samples including 107 diffuse type GCs. The predictive value of the signature was verified using other diffuse type GCs in three independent cohorts (n = 466). Various statistical methods, including log-rank and Cox regression analyses, were used to estimate an association between the signature and prognosis. The signature was also characterized by somatic variant assessments and tissue microarray analysis between diffuse type GC subtypes.
Results
Transcriptomic profiling revealed two distinct subtypes of diffuse type GC including intestinal-like (INT) and core diffuse type (COD) subgroups. We generated a signature, namely COD-signature, reflecting the best characteristics of subtypes. When estimating prognostic value in other cohorts, COD-signature showed a strong predictability and an independent clinical utility in diffuse type GC prognosis (hazard ratio = 2.058, 95% confidence interval = 1.53-2.77, P < 0.001; Table). Integrative mutation and gene expression analyses demonstrated that COD subtype was responsive to chemotherapy, whereas INT subtype showed responsiveness to immunotherapy with immune-check point inhibitor (ICI). Tissue microarray analysis showed practical utility of IGF1 and NXPE2 proteins for predicting diffuse type GC’s heterogeneity.Table: 155P
Univariate and multivariate Cox regression analysis of overall survival in diffuse type gastric cancer
Variables | Univariate | Multivariate | ||||
---|---|---|---|---|---|---|
n | HR (95% CI) | P-value | n | HR (95% CI) | P-value | |
Age | 402 | 1.013 (1.001 - 1.025) | 0.037 | 402 | 1.02 (1.007 - 1.032) | 0.003 |
Gender (Male or Female) | 402 | 1.074 (0.805 - 1.433) | 0.625 | |||
AJCC Stage (I, II, III or IV) | 402 | 2.516 (2.088 - 3.032) | <0.001 | 2.67 (2.204 - 3.235) | <0.001 | |
Tumour site (cardia, body, antrum or whole) | 402 | 0.985 (0.777 - 1.248) | 0.9 | |||
COD-signature (INT or COD subtypes) | 402 | 1.675 (1.257 - 2.234) | <0.001 | 2.058 (1.53 - 2.766) | <0.001 |
Abbreviations: HR, hazard ratio; CI, confidence interval; INT, intestinal-like; COD, core diffuse type.
Conclusions
The COD-signature represents a promising diagnostic tool for the identification of diffuse type GC patients who would display different clinical behaviours as well as response to chemotherapy or ICI treatment.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
Korea Research Institute of Bioscience and Biotechnology Chungnam National University, College of Medicine Seoul National University, Faculty of Medicine.
Funding
Korea Research Institute of Bioscience and Biotechnology.
Disclosure
All authors have declared no conflicts of interest.
Resources from the same session
2262 - Real world experience of Nivolumab therapy in Metastatic Renal Cancer patients: a 3 year multi-centre review
Presenter: Joanna Hack
Session: Poster Display session 3
Resources:
Abstract
4441 - “A pilot study of tremelimumab (treme) with or without cryoablation (cryo) in patients (pts) in metastatic renal cell carcinoma (mRCC).”
Presenter: Matthew Campbell
Session: Poster Display session 3
Resources:
Abstract
2613 - Lenvatinib (Len) alone or in combination with Everolimus (Eve) in heavily pretreated patients (pts) with metastatic renal cell carcinoma (mRCC) after immune checkpoint inhibitors (ICI) and VEGFR-targeted therapies: A single-institution experience
Presenter: Andrew Wiele
Session: Poster Display session 3
Resources:
Abstract
3249 - Weight loss is an underestimated adverse event with cabozantinib in patients with metastastic renal cell carcinoma (mRCC).
Presenter: Emeline Colomba
Session: Poster Display session 3
Resources:
Abstract
2405 - Impact of corticosteroids on nivolumab activity in metastatic clear cell renal cell carcinoma.
Presenter: Felix Lefort
Session: Poster Display session 3
Resources:
Abstract
4020 - Skeletal muscle loss as an adverse event during Cabozantinib treatment in patients with metastatic renal cell carcinoma
Presenter: Carolina Alves Costa Silva
Session: Poster Display session 3
Resources:
Abstract
2407 - Long term relative survival (RS) in patients with primary metastatic kidney cancer (primary mRCC): an analysis of 2,167 patients from the Austrian National Cancer Registry (ANCR).
Presenter: Monika Hackl
Session: Poster Display session 3
Resources:
Abstract
2470 - Advanced renal cell carcinoma: first results from the prospective research platform CARAT for patients with mRCC in Germany
Presenter: Peter Goebell
Session: Poster Display session 3
Resources:
Abstract
1533 - Are immune checkpoint inhibitors a valid option for papillary Renal Cell Carcinoma? Transcriptomic characterization of the immune infiltrate
Presenter: Manon De Vries-brilland
Session: Poster Display session 3
Resources:
Abstract
3367 - Treatment-Free Survival, With and Without Toxicity, as a Novel Outcome Applied to Immuno-Oncology Agents in Advanced Renal Cell Carcinoma
Presenter: Meredith Regan
Session: Poster Display session 3
Resources:
Abstract