The US Cancer Genome Map study found that cancers on some different organs have strong molecular similarities, and some cancers have completely different molecular subtypes although they occur in the same organ.
The “small nodules covered with soybeans and mung beans†“grey white on the cut surface and grayish yellow on the surface of the necrosis†have been used by clinicians as the basis for judging cancer. At the same time, the occurrence of cancer naturally divides treatment methods based on cancerous sites, and lung cancer and gastric cancer belong to different departments for different diagnosis and treatment.
"Cells" recently published the results of the United States Cancer Genome Atlas (TCGA) study but gave a number of different voices. They studied 33 cancer types and more than 10,000 cancer cases and found that some cancers on different organs have Strong molecular similarities, while some cancers occur in the same organ, but they have completely different molecular subtypes.
With the improvement of the level of gene sequencing, people have explored changes in the level of “cancer†DNA molecules to prove that the phenomenon of “homogeneous and heterogeneous†has indeed existed. The deepening of human cognition of life makes the “old language system†that used to describe cancer as an apparent feature, and may face the impact of the “new language system†at the molecular level due to the lack of expression accuracy. What influence does the interaction between "new and old" have on the existing clinical and research?
The classification of cancer is based on the times
"Clear cell papillary renal cell carcinoma" "Thyroid follicular renal cell carcinoma" ... In the 2016 World Health Organization (WHO) kidney tumor classification, kidney cancer includes different subtypes, and cancer cells can be seen from the name. The anatomical shape is used as an important basis for cancer classification.
According to data, the WHO tumor typing standard is a well-recognized type of tumor classification program. It is usually diagnosed by the main histological type of the tumor (>50% of the tissue structure), and it targets different tissues and organs such as lung cancer, colon cancer, Gastric cancer, etc. have corresponding classification standard documents.
In the traditional classification, it is not the WHO's classification standard "unified." Different organs also have different classification criteria of their own characteristics, such as gastric cancer, Lauren classification is widely used in the study. “Lauren is a Nordic pathologist. He proposed Lauren's classification in 1965. According to his own diagnosis and treatment experience and research, he classified the predilection age, the predilection sex, growth and transfer methods.†Shanghai Jiaotong University School of Medicine Yu Yingyan, a professor at Ruijin Hospital of the affiliated company, said that this classification has been highly praised in practice in the field of gastric cancer because of its ease of use and high doctor reproducibility.
Yu Yingyan had conducted a large-sample Lauren categorization study of diagnosed cases in China. After more than 600 patients were followed up for 5 years, the study concluded that the clinical treatment guided by Lauren classification can be used to evaluate the prognosis of gastric cancer. The role.
"The WHO classification scheme is superior to the Lauren classification scheme in that it is advancing with the times." Yu Yingyan said that the WHO will publish a classification scheme based on the latest developments in pathological development, immunopathology and molecular pathology. Revisions are made. In the recent revisions, there will also be a description of the molecular mechanism.
It can be seen that the accurate and comprehensive classification of cancer is one aspect. It is easy to grasp, and different doctors make the same judgment based on the standard, and it will determine whether the classification has greater practical value.
Molecular Technology Creates a New "Language System"
"The concept of tumor molecular typing appeared in a research project published by the National Cancer Institute in the late 1990s." Yu Yingyan said that for the first time it proposed to use molecular techniques to provide more information for tumor classification.
In the process of information acquisition, researchers conduct different levels of research on cancer through technologies such as genomics (DNA), transcriptomics (RNA), proteomics, and metabolomics. In other words, starting from the deepest level of gene mutations, the mechanisms leading to canceration are found layer by layer, and are classified by the “omnidirectional, multifaceted†information obtained.
With the deepening and widespread application of technology, a broader range of plans for precision medical treatment was initiated. Zhu Yanmei, executive vice president of Huada Gene, introduced that the precision medicine program initiated by the United States in January 2015 was actually aimed at cancer. The Second Human Genome Project places great emphasis on the role of the personal genome in precision medicine.
The research involved the acquisition of probes, the acquisition of specific molecular markers, the identification of mutations or deletion fragments, and the effects of changes in these genetic basal substances on levels of RNA and cellular pathways, including their Correspondence with organs, pathology.
TCGA is the first project to study a wide range of cancers at the molecular level, but it is not the only one.
The Asian Cancer Research Group (ACRG) also published a large sample of gastric cancer molecular level study data in May 2015. The analysis of gene expression profiles and gene mutations in gastric cancer specimens of the Samsung Medical Center of Korea was performed, and the gene-related classifications of gastric cancer were performed. Through long-term follow-up, the study also proved that this classification method has a predictive effect on the most concerned issue of the doctor and the patient with “how to treat it to produce better resultsâ€.
“China has also started relevant research and focused on hospitals, medical institutions, and other medical units within the system.†Zhu Yanmei said that BGI has cooperation with a number of research institutes in Shanghai and Guangzhou, and also has cooperation with foreign medical institutions. Whether or not they have jointly deepened the study of tumors from the genetic level.
Large samples, long time, and high investment are the “three mountains†for tumor molecular typing research. Therefore, many research centers are often used for collaborative research.
In May 2017, the United States Food and Drug Administration (FDA) approved for the first time a cross-cancerous immunotherapeutic drug targeting a specific genetic marker: PD-1 monoclonal antibodies pembrolizumab and nivolumab, regardless of whether it is lung cancer, kidney cancer or intestine Cancer, stomach cancer... This is considered the most directly applied clinically approved molecular typing.
"However, this molecular marker does not include most cancer patients." Lu Zhihao, deputy chief physician of Peking University Cancer Hospital explained that, for example, only 4 percent of patients with IV colon cancer are included in this type of treatment.
The data mastered by Yu Yingyan also explains the problem of “a small proportion of people benefiting from it.†“In the current targeted gene therapy for tumors in the United States, 30% to 50% of patients can undergo molecular sequencing techniques such as tumor genome sequencing. Finding genetic mutations in the drive, but only 3% -13% of patients can find the corresponding listed drugs. Overall, the beneficiaries are only less than 5% of the patients."
There is an urgent need for "simultaneous interpretation" of new and old "language" dialogues
Traditional classification is based on the interpretation of imaging and pathology. It is "visible and tangible." For clinicians, through the diagnosis of the patient in the actual diagnosis, you can get "What you see is what you get." Information, used to guide treatment programs, is simple and easy.
Molecular typing is a new concept. In addition to breaking the "consciousness barrier" in existing concepts, the cost and convenience in use are also a necessary "level". "The price of sequencing technology is still high, and it is difficult to popularize applications." Yu Yingyan said, "High-end equipment for molecular typing is not a routine device for clinical testing in general medical institutions."
Not only is the hardware "blocking", "software" is also unsatisfactory.
In fact, more than three years ago TCGA published a new molecular classification for gastric cancer, and gave a molecular probe for judgment. "But it has not been widely adopted in clinical treatment of gastric cancer." Yu Yingyan said, "The reason is that there is no effective dialogue between the two areas of cancer genome detection and clinical diagnosis and treatment. It is difficult for clinicians to determine the molecular subtypes and their familiar clinical pathology. What kind of symmetrical relationship?"
The language basis of one side is "ABC", while the other side is "æ’‡, æº, 横". It is necessary to "simultaneously pass" to match different "languages."
“Needs a genetic information interpreter or genetic information translator somewhere in between.†Yu Yingyan believes that pathologists can play this role by linking molecular typing to traditional clinical pathology types and issuing In the pathology report, both the molecular typing based on gene mutation and the histopathological typing result are shown. "This kind of report is like a movie's 'Chinese-English subtitle' version, which will make it easier for clinicians to choose the right molecular target therapy."
In addition, the molecular classification study itself also has problems that have not yet constituted a complete system. Yu Yingyan believes that the new classification system should be closely linked with clinical pathology information, which can reflect changes in the molecular level, but also instruct clinical diagnosis and personalized treatment or predict prognosis. (Reporter Zhang Jiaxing)
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