Malignant tumor, which is the medical term for cancer, grows quickly and has a high mortality. The effects of cancer on individuals' physical, psychological, and financial status have been severe. According to the International Agency for Research on Cancer's (IARC) most recent report on the worldwide burden of cancer in 2020[1], China accounts for the largest population in the world in both new cases of cancer and cancer-related deaths. There are an estimated 19.29 million new cancer cases globally in 2020, of which 4.57 million (23.7% of the total) are in China. 9.96 million people are estimated to die from cancer worldwide in 2020, with 3 million of those deaths occurring in China, which takes the top spot globally with 30% of all cancer-related deaths.
In light of the current considerations, we felt urged to take action to make the current situation better. We discovered through research and interviews that cancer patients have difficulties to be tested in time because of the expensive diagnosis procedures in qualified hospitals. So the development of a simpler cancer detection system was in urgent need and that’s what our team intended to concentrate on.
Even though not all malignancies have the chances to be cured, individuals frequently have the highest chance of recovery when they receive an early diagnosis. The use of multiple screening models has made it possible to detect cancer earlier. Early breast cancer, colon cancer, cervical cancer, and lung cancer may all be found with mammography, colonoscopy, Pap tests, and low-dose CT scans, respectively.[2] While the aforementioned screening technologies can identify tumors at an early stage, the majority of malignancies are not discovered until symptoms start to show. This is mostly due to the fact that many malignancies do not have noticeable early signs, and individuals frequently dismiss these minor symptoms. And many individuals, especially those who live in underdeveloped areas without access to tertiary hospitals, believe that going to the hospital for a checkup is bothersome if the symptoms are not quite severe. It is also hard to screen for cancer in early stages outside hospitals because these methods for doing so are very expensive, complicated, and only able to identify one type of cancer at a time. Additionally, reliable screening guidelines for many malignancies are still lacking. Overall, simplifying cancer detection approaches and screening for a number of high-risk malignancies are particularly crucial.
Our objective is to use our products in township health facilities. Township health centers are comprehensive institutions constructed by counties or townships for the health management and medical preventions. Located in the rural area, the township health centers cannot fully afford complicate equipment for diseases detection for the villagers. The villagers must travel a long distance to the more distant metropolitan medical institutions for testing due to the subpar medical conditions of rural health centers. As a result, some individuals miss the best timing for therapy because they cannot be tested in a timely manner. At light of the dilemma above, our goal is to give villagers easy-to-use early cancer screening tools that can be used in township health centers to conduct cancer screenings without using exquisite devices.
In order to solve the issues, we plan to develop a quick and practical early cancer screening platform that can be used in township health centers. We use bioinformatics methods to analyze the expression of LINC00857 in various cancers and reveal its potential biomarker function for detection. After collection of blood sample, RT-RPA is applied to amplify the target molecule. Then the CRISPR-Cas14a system is introduced[3], in which Cas14a can be activated by base pairing of sgRNA and target DNA to further cleave non-specific single-stranded DNA in DNA nanostructure. This causes the DNA nanostructure to break down and releases γ-amylase, which subsequently catalyzes the hydrolysis of straight-chain starch to generate quantitative glucose, corresponding to the target level. This is determined by detecting electrical impulses with the following enzyme adsorption electrode glucose sensor.
The outstanding advantages of our scheme include the convenience, specificity, and sensitivity. Because the signal molecules we screened are present in blood, they can be detected using just the subject's blood sample. Furthermore, none of our system's components require exquisite tools or complicate equipment, which makes it entirely in accord with community health centers. We chose RT-RPA amplification at room temperature because it is more effective than PCR amplification and can finish amplification of a certain order of magnitude quickly. Additionally, we selected the Cas14a protein because it has a reduced miss target rate compared to other Cas proteins and a stronger specific recognition capacity for nucleic acid molecules. Therefore, the match of RT-RPA and Cas14a helps enhance the specificity of our project. Plus, the glucose meter was altered to improve its sensitivity, and its detection limit and quantification limit were both increased.
Compared with existing cancer devices, our platform has outstanding advantages for there are no expensive or sophisticated instruments needed in the detection process and no professional requirements for the operator. Moreover, one of our most distinctive strengths is the speed of detection, it will take less than 30min in the final application, making efficient and large-scale preliminarily cancer screening possible in underdeveloped areas with poor medical care. People with cancer screening demand can get results quickly which provides great convenience for users. After adjusting hardware based on the current design, our platform also has the potential for multi-biomarker detection at one time which can further improve its accuracy. Last but not least, our platform is very flexible. In addition to LINC00857 which is used in our project, the platform is applicable to other LncRNA molecules as long as little changes are made. Therefore, this platform can be applied to screen any other diseases as well through biomarker detection, such as atherosclerosis whose biomarkers are also provided in our model part, which greatly broadens its application.
[1]Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, Bray F. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin. 2021, 71(3):209-249.
[2]Schiffman JD, Fisher PG, Gibbs P. Early detection of cancer: past, present, and future. Am Soc Clin Oncol Educ Book. 2015:57-65.
[3]]Harrington LB, Burstein D, Chen JS, Paez-Espino D, Ma E, Witte IP, Cofsky JC, Kyrpides NC, Banfield JF, Doudna JA. Programmed DNA destruction by miniature CRISPR-Cas14 enzymes. Science. 2018, 362(6416):839-842.