Professor Jun Yu: towards early detection of colorectal cancer
Gastrointestinal cancer comprises gastric cancer, colorectal cancer, and liver cancer. Colorectal cancer is the most common cancer in Hong Kong, having overtaken lung cancer. It accounted for 16.8% of all new cancer cases in 2014. Liver cancer is the third most fatal cancer and gastric cancer the sixth.
The local cancer burden continues to rise at an alarming rate of 18% over the decade. Combined with the fact that the human gut harbours approximately 20% of all cancers, advancement in study and treatment of cancer has an amplified urgency.
Early detection is key.
Yu’s team focuses on the molecular pathology, an emerging discipline within pathology that examines the molecules within the organs and bodily fluids. “Samples of blood, stool, and tissues are taken from cancer patients and lab animals, which are then tested for presence or marked prevalence of certain DNA and RNA sequences,” Yu says. Such identification of oncogene, or cancer-causing genes, has critical implications in cancer diagnosis and treatment.
For instance, a micro-RNA marker Yu has discovered is currently undergoing development by a Shenzhen based biomedical company who aims to create a detection kit for the diagnosis of colorectal cancer by testing a stool sample. Micro-RNAs are 18-25 nucleotides, or building blocks of DNA, that regulate the translation of genes. When a patient develops tumour, alterations in the molecules of RNA due to the tumour can be detected in stool. Yu and her team reported on the detection of stool-based factors such as miR-92a, miR135b and miR-221 in colorectal cancer patients.
Detection by screening for miRNA in stool samples can address the shortcomings in current methods in that it is non-invasive but sensitive. Moreover, molecular change can indicate the presence of cancer or propensity to develop cancer at an even earlier stage.
“Early detection is key. That is why we spend a lot of time and energy studying the molecular basis of cancer development so as to identify the marker,” emphasized Yu of the importance of early diagnosis. The stool-based detection kit is currently awaiting approval by the China Food and Drug Administration.
Yu also studies RNF180, a gene located in the fifth chromosome. It is implicated in various biological processes including cell growth and carcinogenesis. Patients develop cancer when the tumour-suppressing genes lose its function and instead oncogene is overexpressed. The team’s study demonstrated how RNF180 was frequently silenced or downregulated by methylation.
Methylation is a process by which methyl groups are added to the DNA molecule, which can change the activity of a DNA segment without changing the sequence. When located in a gene promoter, it can repress the transcription of genes. Changes in RNF180 methylation was detected in primary gastric cancers which dysplasia alterations is an early event in gastric carcinogenesis and hence an effective tool in early detection.
Methylated RNF180 DNA can be found in the plasma of the gene, a part of the blood that remains the same in circulation when freshly taken. The research has been developed into a circulation marker that can detect gastric cancer from blood samples. It has recently been approved and is set for clinical practice.
Study of biomarkers such as methylated DNAs and miRNAs are part of larger work Yu’s team conducts in its the larger genome project. It enables engineering on a cellular level to restore the function of cancer-suppressing genes.
“The challenge is to identify how to carry the gene from the outside into the cancer cell. There are different kinds of vectors, or carriers.” Current trend is to use a virus to carry the gene to the targeted region, but viruses have limited lifespan and off-target effect which limit its application. “We cannot have an optimal carrier to deliver the gene to the cancerous region without affecting the other organs.” Injection is also out of the question, since once the virus enters the bloodstream, it can be anywhere. The specific target gene therapy technique is a critical area of future development in the field.
Yu’s future plan aims to elucidate the link between Non-Alcoholic Fatty Liver Disease (NAFLD) and Hepatocellular carcinoma (HCC), also called malignant hepatoma. It is the most common type of liver cancer, caused by viral infection from hepatitis B or C, or the introduction of metabolic toxins such as alcohol.
Yu predicts that due to advancement in vaccination against hepatitis, the new generation will see less HCC caused by viral infection, but an increase in NAFLD induced HCC due to the rising rate of obesity. Fat accumulation in the liver can lead to inflammation and hepatitis, and from this status further develop fibrosis, and finally, liver cancer. Yu plans to clarify whether obesity increases the risk of HCC simply because it promotes inflammation or whether there is another independent factor that can unlock new potential prevention and treatment method.
Professor Jun Yu (Croucher Senior Research Fellow 2016) is a gastrointestinal cancer specialist at the Chinese University of Hong Kong (CUHK). After she completed her Doctor of Medicine (MD) and PhD in Medicine, she spent about two years in Germany and three more years in CUHK as a postdoctoral fellow before joining the University of Sydney as a Senior Research officer. She has been a professor at CUHK since 2011, and currently sits as the director of the research laboratory of the Institute of Digestive Disease at Prince of Wales Hospital.
To View Prof Yu’s Croucher profile, please click here.