Author: Gao Yaoyi
Unit: Department of Clinical Laboratory, Zhongshan Hospital, Fudan University
Colorectal cancer
Colorectal cancer (CRC) has become the third largest cancer in the world[1], and the incidence of CRC in the mainland has also shown a gradual upward trend, seriously endangering the health of the Chinese people. The interim results of the first large-scale CRC patient diagnosis and treatment status survey in mainland China in 2020 showed that 83% of patients were in the middle and advanced stages when they were first diagnosed [2]. The later the CRC stage, the lower the five-year survival rate of patients (Figure 1).
Fig. 1 Five-year survival rate of patients with different stages of CRC after treatment
(Source: Monitoring Data of Cancer Hospital of Chinese Academy of Medical Sciences, Shanghai Cd-operative Center, first affiliated hospital of Sun Yat-sen University-2013)
Traditional tests for CRC include fecal occult blood testing, detection of hematological tumor markers (CEA, CA199, etc.), and colonoscopy (Table 1). Among them, colonoscopy, as the gold standard for CRC diagnosis, has entered the routine physical examination and can detect early lesions. However, due to the invasive nature of colonoscopy, complex intestinal preparation is required before examination, which makes many people daunted. Then, for people who are unwilling or unsuitable for colonoscopy, their early screening for CRC has become an urgent problem to be solved.
Table 1 Advantages and disadvantages of various CRC examination methods
DNA methylation testing
DNA methylation testing has always been a reliable method for finding lesions in the early stages of cancer. As a new non-invasive CRC screening method, plasma Septin9 gene methylation detection is simple and accurate, which can provide a new option for tested populations who are unwilling or unsuitable for colonoscopic screening, and help early screening of CRC.
Septin9 gene methylation
Participates in the early occurrence of CRC
Gene methylation plays an important role in maintaining cellular physiological function, genetic imprinting and embryonic development, and is also one of the important epigenetic modifications that drive the development of cancer. Genetic methylation patterns and levels in patients with CRC changed compared to healthy people (Figure 2).
Fig. 2 DNA methylation occurs in the early stages of CRC[3]
Septin9 is a tumor suppressor gene that encodes multiple subtypes of proteins (e.g., septin9-v1, v2, v3, v4) and functions in chromosomal isolation, DNA repair, migration, and apoptosis. Among them, CpG island methylation in the septin9-v2 promoter region is closely related to the occurrence and development of CRC. When the methylation of the Septin9 gene increases, gene expression will be inhibited, resulting in a decrease in the number of encoded proteins, a decrease in structural stability, and ultimately a cancerous caused by cells.
Septin9 gene methylation test
Supports early screening of CRCs
Methylation changes in the Septin9 gene occur in most patients with early CRC, and even exist in precancerous lesions such as polyps and adenomas. The positive detection rate of methylation of Septin9 gene increased significantly with the increase of CRC staging[4].
According to clinical data certified by the State Food and Drug Administration (CFDA), with colonoscopic/pathological results as the gold standard, the sensitivity of Septin9 gene methylation detection can reach 76.63% and the specificity can reach 95.93% [5].
It is recommended to screen for CRC
Given the application value of Septin9 gene methylation detection in the early screening of CRC, this test has been gradually incorporated into domestic and foreign guidelines.
In 2020, the CRC screening guidelines published by the National Comprehensive Cancer Network (NCCN) mentioned that plasma Septin9 methylation testing is recommended for people who refuse other recommended screening methods (Figure 3).
Figure 3 CRC screening guidelines published by the NCCN
The Guidelines for Screening and Endoscopic Diagnosis and Treatment of Early Colorectal Cancer in China, published in 2014, also stated that plasma Septin9 gene methylation testing can be used for the early diagnosis of CRC (Figure 4).
Figure 4 Guidelines for Early Colorectal Cancer Screening and Endoscopic Diagnosis and Treatment in China and the early CRC screening process
Suitable for people
Septin9 gene methylation detection only needs to collect peripheral blood, extract DNA and perform fluorescence quantitative PCR detection and analysis, which can accurately determine the risk of CRC and achieve early screening of CRC. This test offers significant advantages of simplicity, cleanliness and high detection rates.
recommend
Applicable groups of people are as follows:
Patients who are reluctant to do colonoscopy;
Colonoscopic contraindications in people;
Follow-up of the population after treatment, including assessment of treatment effect and monitoring of recurrence.
In recent years, liquid biopsy technology has become more and more widely used in early diagnosis of tumor screening, recurrence assessment, treatment monitoring and medication guidance. The Department of Clinical Laboratory, Zhongshan Hospital, Fudan University, has carried out Septin9 gene methylation detection, aiming to help early screening and early diagnosis and treatment of CRC, and ultimately improve patient prognosis.
Edited by: Yeah Reviewer: Xiao Ran