Table 1.
Molecular biomarkers in gastric cancer development.
| Molecular Biomarker | Impact on Gastric Cancer Development | Authors |
|---|---|---|
| HER2 | -Amplification and overexpression in GC, the positive cases range from 6% to 30%. -HER2/neu amplification is higher in the intestinal histologic subtype of GC, compared to the diffuse subtype, and is not associated with gender and age, but with the poor survival of GC patients. |
[64,65] |
| p53 | -Mutations in the p53 gene occur in the early stages of gastric carcinoma, and their frequency is increased in advanced stages of cancer development. -TP53-positive patients are also classified as one of the GC subtypes. |
[66,67] |
| PD1 | -The expression of PDL1 is significantly increased in cases with PCNA and C-met expression, EBV-positive, and without metastasis; a better outcome is associated with increased PD-L1/PD-1 expression. | [68] |
| p73 | -The p73 gene is not an object of genetic modification in gastric carcinogenesis, wild-type p73 is quite often highly expressed in GC tissues by transcriptional induction of an active allele or the activation of a silent allele. | [69] |
| mdm2 | The expression level of the MDM2 protein is importantly increased in intestinal metaplasia and gastric carcinomas in comparison to simple intestinal metaplasia and chronic gastritis. | [70] |
| Bcl-2 | Lymph node metastases, depth of invasion and the negative expression of Bcl-2 are associated with an increased chance of cancer recurrence. | [71] |
|
pRb
CCND1 |
-Cyclin D1 is a positive regulator of the cell cycle process; retinoblastoma protein (pRb) acts as cell cycle repressor, it promotes G1/S arrest and growth restriction through the inhibition of the E2F transcription factors; their higher expression is merged with cell overgrowth and cancer development. -The expression of pRb and cyclin D1 might be present in the early stages of gastric carcinogenesis, with the higher expression of Rb and cyclin D1 among nonneoplastic mucosa comprising dysplasia, intestinal metaplasia, atrophy and gastritis to carcinoma. |
[72,73] |
| p16 | The p16 gene plays a main role as a tumor suppressor gene, the deletion of the p16 gene is associated with the carcinogenesis process, as well as the progression of gastric carcinoma. | [74] |
| p27Kip1 | Cyclin-dependent kinase inhibitor 1B, called p27Kip1 with low protein expression in GC, is assigned to advanced tumors, it is importantly higher in weakly differentiated cases and is described as a negative prognostic factor for the survival of patients. | [75] |
| MUC | Mucins are a group of extracellular, huge molecular weight, strongly glycosylated proteins; they have significant characteristics assigned to cell signalling, the creation of chemical barriers, facilities to create a gel, a major function related to lubrication. One of their main roles is also as an inhibitory function, and the high expression of mucin proteins, like MUC1, MUC2, MUC5AC and MUC6 is associated with gastric carcinogenesis process. | [76,77] |
| MRP2 | The overexpression of MRP2 is significant in the initial absence of reaction to chemotherapy treatments of tumors, which allow us to consider it as an important biomarker for chemotherapy response. | [78] |
| MDR1 | MDR1 is a very significant candidate gene in the progress of GC susceptibility, as well as displaying an important impact on drug resistance response, and the knockdown of MDR1 might reverse this phenotype among GC cells. | [79,80] |
| GST-P | The expression of GST-P is visibly increased in tumors that are chemically induced, it is also associated with tumor invasion and recurrence, as well as poor prognosis. | [81,82] |
| MSI | -Microsatellite instability (MSI) is an important indicator of the DNA mismatch repair deficiency, which is an agent in the higher accumulation of genetic alterations in gastric carcinogenesis; MSI-positive patients do not have a high content of targeted mutations, some of them were detected in PIK3CA, EGFR, ERBB3 and ERBB2 genes. -GC cases with a high MSI can have long-term survival, regardless of the positive resection margin status. |
[83,84] |
Abbreviations: HER2—tyrosine kinase-type cell surface receptor, p53—tumor protein p53, PD-1—cell surface receptor programmed death-1 and its ligand (PDL1), p73—tumor protein p73, mdm2—murine double minute gene 2, Bcl-2—B-cell lymphoma 2, pRb—retinoblastoma protein, CCND1—cyclin D1 gene, p16—cyclin dependent kinase inhibitor 2A, p27Kip1—cyclin-dependent kinase inhibitor 1B, MUC—mucin, MRP2—multidrug resistance-associated protein 2, MDR1—multidrug resistance 1 gene, GST-P—glutathione S-transferases Pi, MSI—microsatellite instability, PIK3CA—phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha, EGFR – epidermal growth factor receptor, ERBB3—Erb-B2 receptor tyrosine kinase 3, ERBB2—Erb-B2 receptor tyrosine kinase 2.