Women in science: AI unlocks genetic keys to better colorectal cancer survival

Colorectal cancer (CRC) is one of the leading causes of cancer-related deaths worldwide, with approximately 20% of patients presenting with metastatic disease at the time of diagnosis. Despite the cancer's long progression time—often 5-10 years—the majority are found late, making early detection crucial for improving survival rates. Early screening, combined with genetic testing, enables clinicians to make more informed decisions, ultimately improving patient survival.

Dr. Lin Cong, a leading research scientist from BGI Genomics' Institute of Intelligent Medical Research (IIMR), is at the forefront of a transformative CRC study. This collaborative research with Sweden's Uppsala University was published in Nature, in 2024. The cohort involves 1,063 CRC patients and genetic profiling, which could revolutionize how we approach prevention, diagnosis, and treatment. In this interview, Dr. Lin shares insights into how her research is shaping the future of personalized cancer care.

Novel Driver Genes for Early Intervention

Through the study, Dr. Lin's team identified several key genetic alterations specific to CRC, including mutations in pathways like WNT, EGFR, TGFβ, and even mitochondrial genes. These mutations play a crucial role in disease progression and could be used for better early detection and treatment.

"We've discovered mutations in genes like APC, TP53, and KRAS that tend to appear early in cancer's development, and we also identified mutations that emerge later. which could be targets for more advanced therapies," said Dr. Lin. "These findings offer critical guidance for early detection strategies and identify key events relevant to CRC invasion and metastasis."

New Prognostic Subtypes Guide Personalized Treatment

In the research, Lin Cong's team analyzed tumor gene expression profiles and identified five prognostic subtypes with distinct molecular characteristics, known as Colorectal Cancer Prognostic Subtypes (CRPS). This new system allows for more accurate prediction of patient outcomes compared to existing methods.

The widely used Consensus Molecular Subtypes (CMS) classification system categorizes CRC into four molecular subtypes based on gene expression patterns. While CMS classification provides a useful framework, the CRPS system offers more precise prognostic predictions by integrating independent cohort transcriptome data.

"By analyzing CRC at a deeper genetic level, we can personalize treatment more effectively," Dr. Lin explained. "Our system, CRPS, goes beyond the Consensus Molecular Subtypes (CMS) classification, providing a clearer picture of each patient's prognosis. Some tumors classified under CMS4, which are typically considered aggressive, were reclassified as CRPS2, a subtype with a better prognosis." This study presents a more refined prognostic stratification system, which holds significant potential for clinical precision treatment.

Early Screening for Better Survival Outcomes

Dr. Lin emphasizes the importance of early detection of CRC, which is often diagnosed too late due to its subtle onset. She noted that, despite the disease's long progression time, patients frequently present with metastasis at diagnosis, which significantly reduces treatment effectiveness.

Sweden has made significant strides with its nationwide colorectal cancer screening program, showing promising results in reducing cancer incidence and mortality. A large Swedish study, published in JAMA Network Open in February 2024, reveals that cancer-specific mortality decreased significantly by 14% in patients who underwent early screening for CRC, as compared with a control group that received late or no invitations to participate in screening. Excess mortality decreased by 16% in the exposure group.

However, there is still room for improvement in ensuring consistent implementation across regions and boosting participation rates. Another study exploiting the time lag in the implementation of organized screening in Sweden found that areas such as Stockholm and Gotland, which began offering screening in 2008, showed a 14% reduction in long-term colorectal cancer mortality compared to regions that started screening later.

"The current trend in public education about colorectal cancer is encouraging, but we need to do more to raise awareness of early screening. In addition to conventional treatments, specific subtypes of early-stage CRC can be treated with immunotherapy, improving patient survival rates." Dr. Lin said. "Therefore, early screening and prevention are crucial for enhancing survival outcomes."

An AI-driven Future for Diagnosis and Treatment

"This is within reach," Dr. Lin said confidently. "We aim to develop a universally applicable AI model in the next 3-5 years. It will enable faster, more accurate diagnoses, offering clinicians the ability to make data-driven decisions that can transform patient care."

Dr. Lin explained that the AI model will be trained using a vast amount of spatial-temporal omics data, including information on patient cell morphologies, genetic alterations, and gene expression patterns. This technology could one day be used to determine whether a patient has cancer, identify the stage or grade of the disease, and even pinpoint specific target gene mutations from a single biopsy.

"Once we establish this model for CRC, it can be adapted for use in other cancers and diseases," Dr. Lin concluded. "This technology will allow clinicians to predict disease occurrence, monitor progression, and select the best treatments for each individual, leading to more effective, personalized healthcare."

Dr. Lin‘s work is just the beginning of what promises to be a significant shift in how CRC, and even cancer in general, is understood and treated. The integration of genetic data, AI, and lifestyle factors will not only improve patient outcomes for CRC but could eventually be expanded to other diseases in the future.

About BGI Genomics

BGI Genomics, headquartered in Shenzhen, China, is the world's leading integrated solutions provider of precision medicine. Our services cover more than 100 countries and regions, involving more than 2,300 medical institutions. In July 2017, as a subsidiary of BGI Group, BGI Genomics (300676.SZ) was officially listed on the Shenzhen Stock Exchange.