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Transcriptomic Profiling Identifies a Risk Stratification Signature for Predicting Peritoneal Recurrence and Micrometastasis in Gastric Cancer

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Abstract
Purpose: Gastric cancer peritoneal carcinomatosis is fatal. Delay in detection of peritoneal metastases contributes to high mortality, highlighting the need to develop biomarkers that can help identify patients at high risk for peritoneal recurrence or metastasis.

Experimental Design: We performed a systematic discovery and validation for the identification of peritoneal recurrence prediction and peritoneal metastasis detection biomarkers by analyzing expression profiling datasets from 249 patients with gastric cancer, followed by analysis of 426 patients from three cohorts for clinical validation.

Results: Genome-wide expression profiling identified a 12-gene panel for robust prediction of peritoneal recurrence in patients with gastric cancer (AUC = 0.95), which was successfully validated in a second dataset (AUC = 0.86). Examination of 216 specimens from a training cohort allowed us to establish a six gene-based risk-prediction model [AUC = 0.72; 95% confidence interval (CI): 0.66-0.78], which was subsequently validated in an independent cohort of 111 patients with gastric cancer (AUC = 0.76; 95% CI: 0.67-0.83). In both cohorts, combining tumor morphology and depth of invasion further improved the predictive accuracy of the prediction model (AUC = 0.84). Thereafter, we evaluated the performance of the identical six-gene panel for its ability to detect peritoneal metastasis by analyzing 210 gastric cancer specimens (prior 111 patients plus additional 99 cases), which discriminated patients with and without peritoneal metastasis (AUC = 0.72). Finally, our biomarker panel was also remarkably effective for identifying peritoneal micrometastasis (AUC = 0.72), and its diagnostic accuracy was significantly enhanced when depth of invasion was included in the model (AUC = 0.85).

Conclusions: Our novel transcriptomic signature for risk stratification and identification of high-risk patients with peritoneal carcinomatosis might serve as an important clinical decision making in patients with gastric cancer.
Author(s)
김광수김병식우양희육정환이인섭이현이허훈Ajay GoelMitsuro KandaYasuhiro Kodera
Issued Date
2021
Type
Article
Keyword
Gastric CancerCancer
DOI
10.1158/1078-0432.CCR-20-3835
URI
https://oak.ulsan.ac.kr/handle/2021.oak/8527
https://ulsan-primo.hosted.exlibrisgroup.com/primo-explore/fulldisplay?docid=TN_cdi_crossref_primary_10_1158_1078_0432_CCR_20_3835&context=PC&vid=ULSAN&lang=ko_KR&search_scope=default_scope&adaptor=primo_central_multiple_fe&tab=default_tab&query=any,contains,Transcriptomic%20Profiling%20Identifies%20a%20Risk%20Stratification%20Signature%20for%20Predicting%20Peritoneal%20Recurrence%20and%20Micrometastasis%20in%20Gastric%20Cancer&offset=0&pcAvailability=true
Publisher
CLINICAL CANCER RESEARCH
Location
미국
Language
한국어
ISSN
1078-0432
Citation Volume
27
Citation Number
8
Citation Start Page
2292
Citation End Page
2300
Appears in Collections:
Medicine > Medicine
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