Team:XHD-WS-Wuhan-A/Description
Description
Project Inspiration and Description
During the past 7 months, we worked on our project, which is about early diagnose and future therapy of Gastric Cancer. Our goal is to find out a cost efficient, painless and convenient way to diagnose Gastric Cancer through measuring the amount of micro-RNA in a Gastric Cancer cell.
The Background Story
The topic of our project came up from a simple conference. During the winter holiday, when our team sat together and discussed the project, one of our group members, Zimo, brought up the topic of Gastric Cancer.
She told us that one of her middle school classmates discovered that she had Gastric Cancer just after graduating. Her classmate had a bad eating habit, she would only eat lunch on some days, while eating four to five meals on other days. She loved spicy food, and would always eat them with ice cream. Her classmate was diagnosed with depression two years before, and she almost broke down after knowing that she was diagnosed with Gastric Cancer. She started to text Zimo in the middle of the night, saying words like “goodbye” and “take care”. This made Zimo very nervous. About a month later, she told Zimo that the hospital had misdiagnosed, she only had gastritis instead of Gastric Cancer.
Just as she finished the sentence, another group member, Shiqing commented that her cousin went to the hospital last week to get his stomach checked. He was complaining to me hop much pain the gastroscope had caused him.
After hearing the two girls we raised a question about Gastric Cancer. Is there a diagnosing method, that not only the result will be more accurate, but also the patient would feel better?”
After our director heard about our chat, she thought that it was a great topic that worth researching, it would also be a good idea to add in a future therapy plan. Therefore, we determined our project topic—Early Diagnose of Gastric Cancer and Future Therapies.
Gastric Cancer
To work on the project, first we need to have a basic knowledge of Gastric Cancer. Gastric Cancer (or sometimes referred as GC), is one of the most commonly diagnosed cancers worldwide. It is develops from the cell lining of the stomach. A contributing factor of GC is the Helicobacter Pylori, which is a type of bacteria that could remain in the stomach and cause chronic inflammation (also called gastritis) or ulceration[1]. The symptoms of GC would be abdominal pain or discomfort, unexplained weight loss, a sense of fullness even after a small meal, heartburn, indigestion, vomiting blood, poor appetite and digestion, anemia and sometimes visible swelling in the abdomen.
Incidence and Mortality of Gastric Cancer
After knowing the basics of Gastric Cancer, we discovered the morbidity of Gastic Cancer. Overall, gastric cancer incidence and mortality have fallen dramatically over the past 70 years. However, despite its recent decline, gastric cancer is still the fourth most common cancer and the second leading cause of cancer-related death worldwide. In 2000, about 880 000 people were diagnosed with gastric cancer and approximately 650 000 died of the disease[2].
The highest stomach cancer incidence and mortality rates among both males and females are found in Eastern and Western Asia, Latin America, and some former Soviet European countries [3] .
Japan has the highest incidence rate for GC — 69.2 per 100,000 men and 28.6 per 100,000 women[4]. In China alone, an estimated number of 0.4 million cases of GC were diagnosed in 2005, and the mortality to incidence rate ratio was at a high value of 0.75[5].On the other hand, comparing with East Asian countries, the United States has a relative lower incidence for GC — based on the 2012-2016 cases, 10 and 5.3 out of 100,000 men and women respectively were diagnosed with the disease; 4.2 and 2.3 out of 100,000 men and women respectively died from it. The 2019 estimated new cases of GC is 27,510, only ranked 15th and accounts for 1.6% of all cancer types across the U.S[6].
Current Detection methods For Gastric Cancer
There are, currently, numerous detection methods for Gastric Cancer, such as histopathology, endoscopy, upper gastrointestinal series, and other methods including computed tomography and magnetic resonance imaging. Of these methods, histological study of gastric mucosa is recognized as a common approach for detecting atrophic gastritis (AG) and intestinal metaplasia (IM), which are the most symbolic risk factors of GC[7]. However, this method is too invasive for the body therefore not fit to be applied in population screening. As a result, endoscopy becomes a good substitution because it could detect symptoms of GC without performing a biopsy. Nevertheless, endoscopy comes with its drawback as well: its results are highly uncorrelated with those of the histological studies. Another early detection method could be an upper gastrointestinal series, which is a radiologic test that is widely used for diagnosis of GC for its high sensitivity and non-invasiveness[8]. An upper gastrointestinal series generally requires the patient to swallow a highly concentrated barium solution which will coat the organs of the gastrointestinal tract and reflect the motion, inside wall lining, and shape of these organs through fluoroscopy[9].
Current Treatments For Gastric Cancer
Endoscopic treatment, including endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD), is a primary treatment method for early stage non-metastatic gastric cancer. If not suitable, patients could also be treated with laparoscopy and laparotomy, which are more invasive methods in nature than an endoscopic treatment. In addition, for locally advanced GC, a postoperative adjuvant chemotherapy should be performed following gastrectomy. For patients having metastatic GC, palliative surgery and radiotherapy are recommended to prolong and enhance the quality of life[10]. Take in consider of all the pain and great inconvenience that come along with cancer treatments, better early detection methods of such disease should be researched and brought to reality to eliminate advanced stage tumor as much as possible.
Therefore, our team is committed to design a new model based on new biomarkers that can diagnose gastric cancer with specificity, accuracy and ease, which also has the potential to be used in cancer treatment in the future.
MicroRNA and Gastric Cancer
Before introducing our project, we should first know concept of micro-RNA. MicroRNAs (miRNAs) are small (~22 bp) nucleic acids that function by regulating the expression. More and more studies indicated certain types of microRNA expression are discovered to be correlated with the progression of various cancers, including GC[11]. Their dysregulation has been reported to be involved in pathogenic processes underlying GC tumorigenesis and progression, including cell growth, invasion, metastasis, and apoptosis, which indicates that miRNA has the potential to become candidates for diagnostic, prognostic, and predictive biomarkers. Many miRNAs are differentially expressed between GC tissues and corresponding normal gastric tissue from the same patient, suggesting the diagnostic and prognostic values of miRNAs in clinical applications. miR-21 and miR-17 levels in GC were found to be significantly associated with all tumor stage[12]. In addition, some studies indicated that miR‑196a and miR‑148a were upregulated in the early GC samples. hsa‑miR‑196a and hsa‑miR‑148a have the potential to serve as candidate biomarkers for early GC[13]，[14]. That has inspired us to use miRNAs as biomarkers to be used in diagnosing and treatment of GC.
Our Project
After all the discussion about on Gastric Cancers and micro-RNA, our project should be introduced. Previous studies indicated miRNAs can serve as a potential source for biomarkers for detection of human malignancies, including GC, miRNA sensor contain complementary binding sites to a miRNA of interest, which inhibit miRNA activity. When perfectly matched, binding sites will bind to the target miRNA preventing it from binding to their target mRNAs and to perform mRNA silencing. This mechanism gives rise to our idea of fusing DNA sequences with binding sites complementary to miRNA to a plasmid that has reporter gene, for example EGFP-C1, which will monitor the expression of miRNAs in the cells.
We chose four miRNAs (miR-17, miR-21, miR-196a and miR-148a) expressed in patients serum of different stages of GC and established four miRNA sensors to detect these miRNAs in GC cells. Our project may provide a new non-invasive method to diagnosis gastric cancer in early stage in the future.
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[6]https://seer.cancer.gov/statfacts/html/stomach.html
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[8] Haeng L J,Kim J G,Hye-Kyung J,et al.Clinical Practice Guidelines for Gastric Cancer in Korea: An Evidence-Based Approach[J]. Journal of Gastric Cancer, 2014, 14(2):87-104.
[9]https://www.hopkinsmedicine.org/health/treatment-tests-and-therapies/upper-gastrointestinal-series
[10]Wang F H,Shen L,Li J,et al.The Chinese Society of Clinical Oncology (CSCO):clinical guidelines for the diagnosis and treatment of gastric cancer[J].Cancer Communications,2019,39(1):10.
[11] Ueda T,Volinia S,Okumura H,et al.Relation between microRNA expression and progression and prognosis of gastric cancer: a microRNA expression analysis[J].Lancet Oncology.2010,11(2):136-146.
[12] Chen S L,Zhu J M,Yu F F,et al.Combination of miRNA and RNA functions as potential biomarkers for gastric cancer[J]. Tumor Biology, 2015, 36(12):9909-9918.
[13] Zheng G, Xiong Y,Xu W,et al.A two-microRNA signature as a potential biomarker for early gastric cancer[J]. Oncology Letters, 2014, 7(3):679-684.
[14] Tseng C W,Lin C C,Chen C N,et al. Integrative network analysis reveals active microRNAs and their functions in gastric cancer[J]. Bmc Systems Biology, 2011, 5(1):99.
Image: Stomach Cancer Death Per Million Person in 2012
Retrieved from: www.meiyujiankang.cn/cases/53.html
Address
XHD-WS-Wuhan-A
Wuhan High School
No.538,Gongxiu Road,Xiaoshan District,
Wuhan,Hubei Province,China