Team:YiYe-China/Description
Colorectal Cancer
Our aimed project is the non-invasive detection of colorectal cancer (CRC). Currently, irregular eating and resting habits cause CRC, one of the most common global cancers which has a soaring death rate. Indeed, CRC is the second leading factor of cancer death in the United States. According to ASCO (American Society Of Clinical Oncology), it is estimated that 149,500 adults in the United States will be diagnosed with colorectal cancer, and 52,980 deaths (28,520 men and 24,460 women) will be attributed to colorectal cancer in 2021, which makes the death rate to almost 35%.[1] Even worse, there is a clear tendency for the young to be diagnosed with CRC. Based on the statistics, incidence rose by 2% each year in adults under age 50 and 1% in adults age 50 to 64 from 2012 to 2016, and the trend seems to be increasing by year.[2] As the saying goes, "If bread is the first necessity of life, recreation is a close second," the colon and the rectum play critical roles in our digestive system; therefore, if our alimentary canal is ill, we would no longer be able to savor the food.
CRC took away lives
If we look through the previous records, there are many CRC cases that took away many people's lives. For instance, famous British actress Audrey Hepburn, providing us impressive classic movies, such as "Roman Holiday," "Wait Until Dark," Sabrina," etc., and receiving the 65th Academy Awards, passed away aged 63 in Switzerland, despite her struggle with CRC for five years.[3]
In addition, last year, on August 29th, many Marvel fans were struck by heartbroken news: Chadwick Boseman, who embodied Black icons, died of colon cancer, aged only 43 years old. Bosman had played a lot of roles, like "Black Panther," Marshall," all series of "Avengers." His sudden death, without doubt, was significant devastation for his fans. In China, famous CGTN anchor producer Xiaolin died of CRC in 2017, aged 55; Chinese woman basketball player Luyun Cheng died in 2016, aged only 38; Junyao Wang, CEO of Junyao Group, died in 2004, aged 38 as well ...
Detection
We feel distressing when so many people worldwide have been suffering from CRC, but meanwhile, it also offers us an idea for our iGEM project. We decided to focus on the detection tests of CRC. Reading through scores of documents, we found a distinct reason of the high death rate of CRC: late diagnosis. When Hepburn went to the hospital for physical checkout, the cancer polyp was found spreading in her body for five years; the cancer stage was already severely complicated. Same with Boseman. He was diagnosed with stage III colon cancer in 2016 and battled with it these last four years as it progressed to stage IV. [4]
We can't help but wonder what makes these patients miss the best time for treatment? We've learned that the symptoms of early CRC are not obvious, and some of the symptoms are similar to those of other diseases. Thus, it is common to cause misdiagnosis, delayed diagnosis, or complete failure to diagnose. [5] Though the percentage of CRC misdiagnosis for adults is 0.007, according to LiveScience, it is still important to note that a misdiagnosis'' consequences are often severe, considering that if the cancer is caught in the late stages, the survival rates aren't as high. [6]
For instance, several patients with colon cancer have been misdiagnosed with inflammatory bowel diseases (IBD) such as irritable bowel syndrome, diverticulitis, and colitis. Other conditions such as hemorrhoids may also be misdiagnosed. People also confound CRC with hemorrhoids, also known as piles.(6) With similar symptoms, such as severe abdominal pain, changes in bowel habits, and rectal bleeding, it is not surprising that patients with CRC were misdiagnosed, leading to severe consequences down the road. Besides, although the current detection tests are advanced enough, these methods frightened patients. The discomfort people feel after colonoscopy, like bloating or stomach cramping, hinders people from screening.[7] Radiation from CT/ MRI scans or certain eating restrictions before testing makes patients unwilling to get tested. All these pitfalls eventually lead to delay diagnosis for patients, resulting in cancer spreading, complications, and death.
Therefore, our project strives to use stool testing, a non-invasive method, to detect CRC.
Theory
Currently, the most common detection using stool is the FOBT (fecal occult blood testing). However, its sensitivity is relatively low, and not all cancers or polyps bleed. Based on research in Taiwan, the sensitivity of detection of total colorectal neoplasia and advanced neoplasia was 6.98% and 22.1%, respectively,[8] which is not enough compared to the accuracy of colonoscopy. Besides, since the fecal occult blood test can only detect the presence or absence of blood while unable to determine what's causing the bleeding, many other diseases (like those mentioned above) all include different degrees of occult bleeding, leading to false-positive results. Likewise, the fecal occult blood test could show a negative test result when cancer is present (false-negative result) if your cancer or polyps don't bleed.[9]
We hope to detect cancer polyps through DNA methylation and a toehold switch bonding with a fluorescent protein, mCherry, on its tail to prevent any mentioned defects. Previously, reporters identified that syndecan-2 (SDC2) and tissue factor pathway inhibitor 2 (TFPI2) were two essential DNA for CRC detection. [10] People with CRC polyps have a distinct degree of TFPI-2 and SDC2 than healthy people. As the cancer polyps could excrete along with feces from the surface of our intestines, we aim at probing the role and efficiency of the methylation status of SDC2 and TFPI-2. Then by doing DNA bisulfite conversion and PCR amplification of the methylated DNA, we can compare them with a standard DNA sample to see if it is positive or negative. In addition, we aim to make the methylated DNA glow by using a toehold switch so that the detectors could easily recognize the potential cancer cells.
Compared to current detection tests, stool testing is less uncomfortable and easier to carry out for patients. There are fewer requirements for fancy equipment, so almost every health center would be able to implement this testing. In such a way, more people would be willing to get tested when feeling sick. Consequently, the death rate of CRC will decrease as the polyps would be detected earlier and more treatments could be provided.
Reference:
[1] “Colorectal Cancer: Statistics.” Cancer.Net, Jan. 2021, www.cancer.net/cancer-types/colorectal-cancer/statistics. [2] “Cancer Map Stories.” Colorectal Cancer in Young Adults, gis.cancer.gov/mapstory/CRC/index.html. [3] “Actress Audrey Hepburn Dies.” History.com, A&E Television Networks, 13 Nov. 2009, www.history.com/this-day-in-history/actress-audrey-hepburn-dies. [4] Chang, Rachel. “Chadwick Boseman's Private and Courageous Cancer Battle.” Biography.com, A&E Networks Television, 9 Dec. 2020, www.biography.com/news/chadwick-boseman-colon-cancer-battle. [5] Yuen, Vivian. “A Crisis in Colon Cancer Care: Misdiagnosis Strides for Life Colon Cancer Foundation Burlingame, CA (650) 692-3700.” Strides for Life Colon Cancer Foundation, 13 Jan. 2018, www.stridesforlife.org/crisis-colon-cancer-care-misdiagnosis. [6] “Colon Cancer Misdiagnosis - Symptoms and Treatment.” Paul & Perkins, paulandperkins.com/colon-cancer/. [7] Matta, Harshil. “Colonoscopy: Procedure, Preparation, Side Effects, Recovery, and More.” Medical News Today, MediLexicon International, 21 July 2020, www.medicalnewstoday.com/articles/colonoscopy. [8] Chen, Yi-Yuan, et al. “Accuracy of Immunochemical Fecal Occult Blood Test for Detecting Colorectal Neoplasms in Individuals Undergoing Health Check-Ups.” Advances in Digestive Medicine, No Longer Published by Elsevier, 12 July 2014, www.sciencedirect.com/science/article/pii/S2351979714000450. [9] “Fecal Occult Blood Test.” Mayo Clinic, Mayo Foundation for Medical Education and Research, 12 May 2020, www.mayoclinic.org/tests-procedures/fecal-occult-blood-test/about/pac-20394112. [10] Zhang, Weisong, et al. “SDC2 And TFPI2 Methylation in Stool Samples as an Integrated Biomarker for Early Detection of Colorectal Cancer.” Cancer Management and Research, Dove, 30 Apr. 2021, www.ncbi.nlm.nih.gov/pmc/articles/PMC8096344/. [11]Top picture citation from https://www.unitypoint.org/livewell/article.aspx?id=88319062-5f4d-41b1-bc34-e25f6d872f85.
Project Description
- Colorectal Cancer
- CRC took away lives
- Detection
- Theory
- Reference