Classical biomarkers and non-coding RNAs associated with diagnosis and treatment in gastric cancer

Abstract

One of the most prevalent malignant tumors worldwide, stomach cancer still has a high incidence and fatality rate in China, and the number of young people developing early-onset gastric cancer is steadily increasing. The 5-year survival rate of stomach cancer is typically 30%-35%, the prognosis is bad, the patients' quality of life is low, and the progression of advanced gastric cancer cannot be effectively managed despite the use of surgical surgery, chemotherapy, and other medicines. We urgently need molecular biomarkers with high specificity and sensitivity to increase the early gastric cancer detection rate, extend patient survival, and improve patient quality of life. The initial diagnosis of gastric cancer primarily depends on gastroscopy and biopsy, and invasive procedures cause significant discomfort to patients. Similar to this, treating advanced and metastatic stomach cancer is a pressing issue that requires attention. More and more immune checkpoint molecules have been discovered, and corresponding inhibitors are gradually being applied to clinical diagnosis and treatment. Recently, some non-coding RNAs have begun to be used as new targets for the treatment of gastric cancer. Some non-coding RNAs are highly present in the serum or urine of gastric cancer patients and can be used as diagnostic markers or prognostic indicators. Many clinical trials targeting non-coding RNAs have also shown good therapeutic effects. In general, targeting non-coding RNAs has shown good therapeutic effects. The biomarkers for gastric cancer detection and treatment are reviewed in this article, focusing on the new non-coding RNAs used in diagnosis, prognosis, and treatment. Patients with stomach cancer should have access to more precise and efficient diagnosis and treatment choices as a result of ongoing technological advancements and thorough research.

Keywords: Biomarkers; CircRNA; Diagnosis; Gastric cancer; Immune checkpoint molecules; LncRNA; MicroRNA; piRNA.

Figure 1. Statistics on the incidence of malignant tumors in China in 2022. (A) Histogram of the number of malignant tumor cases in China in 2022. (B) Comparison of the number of malignant tumor cases in China by sex in 2022.

Figure 2. Statistics on the number of malignant tumor deaths in China in 2022. Other tumors include oral cancer, nasopharyngeal cancer, gallbladder cancer, laryngeal cancer, bladder cancer, and other malignant tumors, and the proportion of deaths from each malignant tumor in the total number of deaths from malignant tumors is lower than that of gastric cancer.

Figure 3. The pertinent variables, diagnostic techniques, and associated biomarkers in the incidence and progression of cancer of the gastric tract. Classical serum and tissue markers in gastric cancer, associated with early diagnosis, gastric cancer classification, immunotherapy, and prognosis, as well as emerging non-coding RNAs with potential clinical applications. CT, computed tomography; GC, gastric cancer; Hp, Helicobacter pylori; G-17, gastrin-17; CTC, circulating tumor cell; HER2, human epidermal growth factor receptor 2; EGFR, epidermal growth factor receptor; MET, mesenchymal-epithelial transition factor; CLDN18.2, Claudin 18.2; CEA, carcinoembryonic antigen; CA19-9, carbohydrate antigen 19-9; CA-125, carbohydrate antigen 125; CA72-4, carbohydrate antigen 72-4; AFP, alpha-fetoprotein; VEGF, vascular endothelial growth factor; FGFR2, fibroblast growth factor receptor 2; PD-1/PD-L1, programmed cell death protein 1/programmed death-ligand 1; EBV, Epstein-Barr virus; MSI/dmmR, microsatellite instability/ mismatch repair deficiency; TMB, tumor mutational burden. MiRNA, MicroRNA; CircRNA, circular RNA; LncRNA, long non-coding RNA; PiRNA, PIWI-interacting RNA.

Figure 4. The Correa cascade hypothesizes the gradual transformation of normal gastric mucosal cells into malignant tumors, progressing from normal gastric mucosal infection with Helicobacter pylori to non-atrophic gastritis, chronic atrophic gastritis, intestinal metaplasia (precancerous lesions), dysplasia, and finally, enteric gastric cancer. The occurrence of diffuse gastric cancer may be related to Helicobacter pylori infection, which is a direct result of chronic active gastritis [23,24]. Fig. 4 was created by figdraw.com.