Long non-coding RNAs towards precision medicine in gastric cancer: early diagnosis, treatment, and drug resistance

Abstract

Gastric cancer is a deadly disease and remains the third leading cause of cancer-related death worldwide. The 5-year overall survival rate of patients with early-stage localized gastric cancer is more than 60%, whereas that of patients with distant metastasis is less than 5%. Surgical resection is the best option for early-stage gastric cancer, while chemotherapy is mainly used in the middle and advanced stages of this disease, despite the frequently reported treatment failure due to chemotherapy resistance. Therefore, there is an unmet medical need for identifying new biomarkers for the early diagnosis and proper management of patients, to achieve the best response to treatment. Long non-coding RNAs (lncRNAs) in body fluids have attracted widespread attention as biomarkers for early screening, diagnosis, treatment, prognosis, and responses to drugs due to the high specificity and sensitivity. In the present review, we focus on the clinical potential of lncRNAs as biomarkers in liquid biopsies in the diagnosis and prognosis of gastric cancer. We also comprehensively discuss the roles of lncRNAs and their molecular mechanisms in gastric cancer chemoresistance as well as their potential as therapeutic targets for gastric cancer precision medicine.

Identification of a Tumor Microenvironment-relevant Gene set-based Prognostic Signature and Related Therapy Targets in Gastric Cancer

“…Patients suffering from GC often display heterogeneous clinical outcome, with survival durations ranging from less than 5 months to over 10 years 4 , 11 . The 5-year overall survival rate of patients with early-stage localized GC is more than 60%, whereas that of patients with distant metastasis is less than 5% 30 . When diagnosed at early stages, GC can be effectively treated with endoscopic or surgical resection with or without adjuvant therapy.…”

Targeting β-Catenin Signaling by Natural Products for Cancer Prevention and Therapy

“…p53 and Puma) ( Li et al., 2013 ; Qin et al., 2018a ; Wang W. et al., 2018 ; Wang et al., 2020 ; Zhang J. et al., 2020 ). It has also been reported that natural products can enhance the chemosensitivity of cancer cells by suppressing the functions of drug resistance-related proteins ( Feng et al., 2017 ; Dong et al., 2020 ; Yuan et al., 2020 ). Recent studies have identified several natural products with potent inhibitory effects on the β-catenin signaling and shown promising anticancer efficacy in vitro and in vivo , such as baicalin ( Zhou et al., 2017 ), arctigenin ( Lee et al., 2017 ), and rhein ( Liu et al., 2018 ).…”

Disease-Causing Mutations and Rearrangements in Long Non-coding RNA Gene Loci

“…For example, it is conceivable that disease-associated lncRNA gene variants will be used in the future to forecast the success of cancer therapy. In fact, several lncRNAs affected by cancer-relevant SNPs or amplifications and deletions, including H19, PVT1,or ANRIL have been implicated in cancer drug resistance, as extensively reviewed elsewhere (Campos-Parra et al, 2018;Liu et al, 2020;Peng et al, 2020;Yuan et al, 2020). To solidify the clinical utility of these lncRNAs as diagnostic and prognostic markers for defined patient groups, larger cohorts and replication studies are desirable.…”