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.
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:
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.
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.
Mucinous Adenocarcinoma: Characterized by glandular cells producing mucus.
Infiltrative Small Cell Carcinoma: A rare but highly invasive subtype.
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.
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.
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.
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.Early diagnosis of gastric cancer is critical to improving treatment success. A variety of biomarkers play an important role in the early screening and diagnosis of gastric cancer, although they often need to be used in combination with other tests to improve accuracy. Some of the common markers are listed below:
Marker | Definition | Function | Limitations |
---|---|---|---|
CA 19-9 | A glycoprotein | Used to detect tumors of the digestive system, including gastric cancer, and may be elevated especially in advanced gastric cancer | Not specific, may be elevated in advanced stages and may be influenced by other factors |
CEA | Carcinoembryonic Antigen | Expressed in a variety of cancers, including gastric cancer, for monitoring treatment efficacy and assessing the risk of recurrence | Lacks specificity, may also be influenced by other non-cancer factors |
CA 72-4 | A glycoprotein | Used as an aid in the diagnosis of gastric cancer, especially in advanced stages | Not specific, may be elevated in other diseases |
Pepsinogen | Protease secreted by the gastric mucosa | May be decreased in early gastric cancer and is considered an early diagnostic marker | Interfered with by other gastric diseases and factors such as H. pylori infection |
AFP | Alpha-fetoprotein | May be elevated in some rare types of gastric cancer | Lacks specificity and is mainly used to detect specific subtypes of gastric cancer |
MicroRNA | A small molecule of RNA | Studied as a potential diagnostic and therapeutic marker for gastric cancer in recent years | Further research is needed for standardization of the technology and clinical validation |
These markers play an important role in the early diagnosis of gastric cancer; however, they all have limitations and need to be fully evaluated in conjunction with other clinical information and tests.
Other gastric cancer research related genes include:
Metastasis of gastric cancer is the process of spreading cancer cells from the primary site to other sites, which usually involves several complex steps and interactive factors. The following is a detailed description of the mechanisms of gastric cancer metastasis:
Invasion and invasion: The first step in metastasis is the invasion of tumor cells from the primary site into surrounding tissues. This usually involves aggressive growth of tumor cells and invasion of surrounding structures. Cancer cells gain the ability to become invasive by altering the extracellular matrix and cell-cell interactions.
Intravascular metastasis: Once tumor cells have invaded surrounding tissues, they may enter the vascular system or the lymphatic system, spreading through the bloodstream or lymphatic fluids to sites distant from the primary site. This form of metastasis allows tumor cells to establish new foci farther away in the body.
Upstream Regulatory Genes: Abnormal expression or mutation of some genes plays a key role in the metastatic process. For example, inactivation of tumor suppressor genes (TSGs) and activation of tumor promoter genes (oncogene) may prompt tumor cells to metastasize.
Cell-cell interactions: Metastasis also involves the interaction of cancer cells with surrounding normal cells. This includes interactions with immune cells, vascular endothelial cells, etc., through which tumor cells evade immune surveillance and enter the blood or lymphatic system.
Microenvironmental Influences: The characteristics of the tumor microenvironment also influence the success of metastasis. Adequate angiogenesis, a suitable stromal environment, and the presence of immune cells may all play a key role in the development of metastasis.
New organ colonization: Once tumor cells reach a site far from the primary site, they need to colonize and grow in a new organ or tissue. This requires adaptation to the new microenvironment and interaction with surrounding cells.
Studying the mechanisms of metastasis in gastric cancer is crucial for developing prevention and treatment strategies and improving patient prognosis. A deeper understanding of these processes can help develop more targeted therapies to block or intervene in the metastatic process of cancer cells.
Advances in Surgical Treatment:
Despite the fact that 5-year survival rates for early gastric cancer can be more than 90%, the majority of patients still have predominantly advanced gastric cancer due to low rates of early diagnosis.Tan (2019) aims to provide an update on the latest advances in the surgical management of advanced gastric cancer [3].
Impact of eradication therapy on future gastric cancer risk:
Ford et al. (2020) assessed the impact of H. pylori eradication therapy on future gastric cancer risk in patients undergoing endoscopic mucosal resection for gastric tumors [4]. The study included 10 randomized controlled trials of more than 8000 healthy individuals and 1841 patients with gastric tumors.
Gastric Cancer Epidemiology and Screening for Prevention:
Gastric cancer is a global health problem, with more than 1 million people newly diagnosed with gastric cancer worldwide each year.Thrift et al. (2019) reviewed the epidemiology of gastric cancer, as well as screening and prevention efforts to reduce gastric cancer morbidity and mortality globally [5].Wong et al. (2021) analyzed data from global and national cancer registries, including 1980 to 2018 with incidence and mortality data for at least 15 calendar years. Overall, the incidence of gastric cancer has decreased in 29 countries and the mortality rate has decreased in 41 countries [6].Xie et al. (2021) reviewed the current epidemiologic status of gastrointestinal cancers in China, the United States, and Europe, the main risk factors and their distributions in these regions, and described current screening strategies. Gastrointestinal cancers such as gastric, colon, and esophageal cancers are a major medical and economic burden worldwide, with the highest number of new cancer cases and cancer deaths each year [8].
References
[1] Ferlay J, Shin HR, Bray F, et al. GLOBOCAN 2008 v2.0, cancer incidence and mortality worldwide: IARC CancerBase No. 10 [Internet]. Lyon (France): International gency for Research on Cancer, 2010.
[2] Jemal A, Bray F, Center MM, et al. Global cancer statistics [J]. CA Cancer J Clin 2011,61:69–90.
[3] Zhaoyang Tan. Recent Advances In The Surgical Treatment Of Advanced Gastric Cancer: A Review [J]. MEDICAL SCIENCE MONITOR , 2019.
[4] Alexander Charles Ford, Yuhong Yuan, Paul Moayyedi. Helicobacter Pylori Eradication Therapy to Prevent Gastric Cancer: Systematic Review and Meta-analysis [J]. GUT, 2020.
[5] Aaron P Thrift, Hashem B El-Serag, Burden of Gastric Cancer [J]. CLINICAL GASTROENTEROLOGY AND HEPATOLOGY, 2019.
[6] Martin C S Wong, Junjie Huang, Paul S F Chan, et al. Global Incidence and Mortality of Gastric Cancer, 1980-2018 [J]. JAMA NETWORK OPEN, 2021.
[7] Yumo Xie, Lishuo Shi, Xiaosheng He, Yanxin Luo. Gastrointestinal Cancers in China, The USA, and Europe [J]. GASTROENTEROLOGY REPORT, 2021.
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