Abstract
Gastric cancer (GC) is a leading cause of worldwide cancer-related death. Being a highly heterogeneous disease, the current treatment of GC has been suboptimal due to the lack of subtype-dependent therapies. Peritoneal dissemination (PD) is a common pattern of GC metastasis associated with poor prognosis. Therefore, it is urgently necessary to identify patients at high risk of PD. PD is found to be associated with Lauren diffuse type GC. Molecular profiling of GC, especially diffuse type GC, has been utilized to identify molecular alterations and has given rise to various molecular classifications, shedding light on the underlying mechanism of PD and enabling identification of patients at higher PD risk. In addition, a series of diagnositc and prognostic biomarkers of PD from serum, peritoneal lavages and primary GCs have been reported. This comprehensive review summarizes findings on the multi-omic characteristics of diffuse type GC, the clinical significance of updating molecular classifications of GC in association with PD risk and research advances in PD-associated biomarkers.
Highlights
Gastric cancer (GC) is the world’s fifth most commonly diagnosed cancer and third leading cause of cancer-related mortality [1]
Diffuse type was associated with peritoneal recurrence while the intestinal type was recurrence [21]. These findings suggest that further investigations into Diffuse type GC (DGC) may help elucidate associated with distant recurrence [21]
A Whole genome sequencing (WGS)-based study including 49 GC cases showed that DGC is characterized by a significantly lower clonality and amplification and TSC2-RNF216 fusion were reported in DGC [34]
Summary
Gastric cancer (GC) is the world’s fifth most commonly diagnosed cancer and third leading cause of cancer-related mortality [1]. The Asian Cancer Research Group (ACRG) described four subtypes of GC, MSI, MSS/EMT (microsatellite stable/epithelial-to-mesenchymal transition), MSS/TP53+ (TP53 active) and MSS/TP53− (TP53 inactive), based on gene expression profiles [4]. These molecular classifications identified GC subtypes with distinct genotypes and phenotypes, which, in turn, drives research into potential therapeutic targets and subtype-directed management [5]. In the era of precision medicine when novel NGS-based molecular classifications of GC have been recognized, it is of urgent priority to identify molecular characteristics associated with PD risk in GC patients after or even before curative resection, which might improve treatment decision and disease outcomes. Advances in research on diagnostic or predictive PD biomarkers are summarized
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