Gastric Cancer
Gastric cancer is a major health burden worldwide. It is the second cause of cancer deaths after lung cancer [1-2]. Gastric cancer (also known as stomach cancer) is an abnormal growth of cells that begins in the stomach.
In this article, we introduce information related to gastric cancer, including its definition and classification, pathogenesis, molecular biology, signaling pathways, biomarkers, and research advances.
1. Definition and Classification of Gastric Cancer
Gastric cancer is a malignant tumor originating from the tissues of the stomach, usually characterized by abnormal proliferation and uncontrolled cell division of normal gastric tissues. The classification of this cancer is typically based on the tissue type, pathological characteristics, and the extent of spread. Here are some key classifications of gastric cancer:
1.1 Histological Types:
Adenocarcinoma: Adenocarcinoma is the most common type, accounting for the majority of cases. It originates from the glandular cells of the gastric mucosa, forming glandular structures.
Leiomyosarcoma: A rare type that originates from the smooth muscle layer of the stomach.
Gastrointestinal stromal tumor (GIST): Arises from neuroendocrine cells or muscle layers and is distinct from adenocarcinoma.
1.2 Staging System
Gastric cancer is often staged using the TNM staging system, which includes:
T (Tumor): Describes the size and extent of the primary tumor.
N (Node): Describes whether lymph nodes are involved.
M (Metastasis): Describes the presence of distant organ metastasis.
1.3 Other Classifications:
Mucinous Adenocarcinoma: Characterized by glandular cells producing mucus.
Infiltrative Small Cell Carcinoma: A rare but highly invasive subtype.
2. Pathogenesis of gastric cancer
The pathogenesis of gastric cancer is a complex process involving the interaction of many factors. The following are some common pathogenesis of gastric cancer:
Genetic factors: Genetic factors play an important role in the development of gastric cancer. Mutations or genetic variations in certain genes may increase the risk of developing gastric cancer. For example, mutations in TP53 (tumor suppressor gene) are closely associated with the development of gastric cancer.
Helicobacter pylori infection: Helicobacter pylori (H. pylori) is a common bacterium found in the stomach and has been associated with chronic gastritis, ulcers, and some cases of gastric cancer. H. pylori infections cause inflammation of the mucous membranes, which may contribute to the malignant transformation of normal cells in the long term.
Environmental Factors: A number of environmental factors have also been implicated as risk factors for gastric cancer. These include prolonged exposure to strong food preservatives, consumption of unclean foods, prolonged smoking and alcohol consumption. A diet high in salt is also associated with the development of stomach cancer.
Dietary Factors: Diet plays a key role in the development of stomach cancer. Diets high in salt, fat and fiber are believed to increase the risk of stomach cancer. On the contrary, fresh vegetables, fruits and high-fiber foods may be beneficial in preventing stomach cancer.
Inflammation and ulcers: Chronic gastritis and gastric ulcers are precursors to stomach cancer. Long-standing inflammatory conditions may encourage malignant transformation of normal cells.
Chronic anemia: Chronic anemia is highly associated with stomach cancer. Gastric cancer may lead to chronic bleeding, which causes anemia.
The pathogenesis of gastric cancer is a multifactorial process, and the genetic background, lifestyle, and dietary habits of individual patients may all play a role in the development of gastric cancer. Early identification and control of these risk factors are important for the prevention of gastric cancer.
3. Molecular biology
3.1 Genetic variation
Genetic variation in gastric cancer plays an important role in tumor development and progression. Some key genetic variants are closely related to the pathogenesis of gastric cancer.
TP53: TP53 is a gene encoding a tumor suppressor protein, which plays a key role in maintaining genomic stability and preventing cancer progression. In gastric cancer, the mutation frequency of TP53 is high, which may lead to the loss of effective monitoring and control of abnormal cells, thus promoting tumor development.
HER2: HER2 (Human Epidermal Growth Factor Receptor 2) is another gene that has been strongly associated with gastric cancer. Overexpression of HER2 has been linked to the development of some gastric cancers and poor prognosis. Therapeutic agents targeting HER2, such as three thrush and trastuzumab, have been used in some patients with HER2-positive gastric cancer.
3.2 Signaling pathways
Key signaling pathways play a critical role in the regulation of cell growth, differentiation and apoptosis. The following are some important signaling pathways in gastric cancer:
Wnt/β-catenin pathway: This pathway is involved in the development and metastasis of gastric cancer. Under normal conditions, this pathway maintains tissue stability by regulating cell adhesion, proliferation and differentiation. However, in gastric cancer, the Wnt/β-catenin pathway may be over-activated, leading to abnormal cell proliferation and cancer progression.
Ras-MAPK pathway: The Ras-MAPK pathway plays a critical role in cell growth, differentiation and survival. Abnormal activation of the Ras-MAPK pathway has been associated with the development and growth of gastric cancer. This may affect tumor development by promoting abnormal cell proliferation and inhibiting apoptosis.
3.3 Epigenetics
Epigenetics regulates the activity of genes, including DNA methylation and histone modifications. In gastric cancer, aberrant regulation of epigenetics is closely associated with cancer development.
DNA Methylation: DNA methylation is a way of regulating gene activity by adding methyl groups to the DNA molecule. In gastric cancer, hypermethylation of certain key oncogenes may lead to silencing of these genes, thereby promoting tumorigenesis.
Histone Modifications: Histone modifications involve specific chemical modifications to histone proteins that affect chromatin structure and gene expression. In gastric cancer, aberrant changes in some histone modifications may lead to overexpression of oncogenes and promote tumor progression.
These studies at the molecular biology level provide important clues for an in-depth understanding of the pathogenesis of gastric cancer, as well as a basis for the development of targeted and individualized therapeutic strategies.
