Expected to optimize targeted and immunotherapy regimens, Shanghai experts have drawn a genetic variation map of colorectal cancer in China | Rectal Cancer | Variation

Release time:Apr 13, 2024 23:38 PM

Recently, it was reported that Professor Xu Ye from the Department of Colorectal Surgery at Fudan University Affiliated Cancer Hospital, in collaboration with Professor Hu Xin from the Precision Oncology Center, has successfully drawn the largest genome variation map of colorectal cancer in China, revealing the genomic variation characteristics of colorectal cancer in the Chinese population, and identifying genomic markers that can accurately predict the efficacy of targeted and immunotherapy for colorectal cancer. This has broadened the thinking for the basic clinical transformation of colorectal cancer. The relevant research results are published in the internationally authoritative academic journal Gastroenterology.

Colorectal cancer is a malignant disease that seriously threatens the life and health of Chinese residents. With the changes in residents' lifestyles and the improvement of health screening awareness, the number of cases of colorectal cancer in China is increasing. Xu Ye said that high chemotherapy tolerance and high recurrence and metastasis rates are still bottlenecks that hinder the long-term survival of colorectal cancer patients. About 20-25% of patients are accompanied by metastasis at initial diagnosis, while 30% of stage I-III and 65% of stage IV patients experience recurrence or secondary metastasis.

Due to the complex molecular pathogenesis of colorectal cancer, it has a high degree of tumor heterogeneity. Finding personalized tumor targets for colorectal cancer and exploring precise treatment have important clinical translational value.

The reporter learned that precise strategies represented by molecular immunotherapy, targeted therapy, and other treatment methods have been widely carried out in the field of colorectal cancer research. However, the current treatment standards and guidelines mostly refer to the Western population, and the genomic variation profile of colorectal cancer based on the Chinese population is blank.

Professor Xu Ye and Professor Hu Xin conducted a large-scale colorectal cancer specific multi gene testing cohort study based on the Chinese population. The study was based on a prospective cohort of Chinese colorectal cancer patients, including 869 cases, including 586 cases of early and 283 cases of advanced colorectal cancer. The team used 887 gene Panel sequencing to draw a systematic and germline variation map, describing the clinical pathology and genomic variation characteristics of colorectal cancer in the Chinese population. It is reported that this is also the largest prospective targeted sequencing platform and clinical sample queue for colorectal cancer in China to date.

The genetic map shows that in terms of mutations in the colorectal cancer system, the top three mutation frequencies are TP53, APC, and KRAS, respectively. The mutation map of the cancer signaling pathway is significantly different from that of the Caucasian population, presenting unique characteristics of the Chinese colorectal cancer patient population.

In terms of germline mutations, 4.6% of patients carry clear or potentially pathogenic germline mutations related to DNA damage repair pathways, with 27.5% of susceptible gene carriers experiencing "secondary strikes" caused by heterozygous loss or biallelic mutations.

The research results also indicate that BRAF and RBM10 single gene driven mutations are independent prognostic factors for shorter progression free survival in metastatic colorectal cancer. In vitro experiments have found that RBM10 expression deficiency promotes tumor cell proliferation, migration, and inhibits apoptosis. Hu Xin said, "This may be one of the triggers for the recurrence and metastasis of colorectal cancer."

Throughout the study, genomic variation interaction network analysis yielded 65 co-occurrence and 106 mutually exclusive potential functional dependent events. Among them, KRAS/AMER1 and KRAS/APC co-occurrence mutations can accelerate drug metabolism, leading to poor chemotherapy sensitivity and limited clinical benefits.

The team found that combining genomic markers can optimize the prediction of immunotherapy efficacy, and this prediction has been validated in the immune checkpoint inhibitor treatment cohort at our center. Xu Ye said that this discovery suggests that genomic biomarkers can be optimized to predict the efficacy of immunotherapy based on this, and more accurately identify the beneficiaries, providing new hope for the precise diagnosis and treatment of colorectal cancer patients.

The co first authors of the paper are Dr. Guo Linwei, Dr. Wang Yunjin, and Master Yang Wenxiao from Fudan University Affiliated Cancer Hospital.

Why is "Cancer King" immunotherapy ineffective? Fudan Cancer Hospital Reveals New Mechanisms of Immunosuppressive Environment for pancreatic cancer CRIP1 | Tumor | pancreatic cancer
Why is "Cancer King" immunotherapy ineffective? Fudan Cancer Hospital Reveals New Mechanisms of Immunosuppressive Environment for pancreatic cancer CRIP1 | Tumor | pancreatic cancer

Immunotherapy has been proven to achieve significant therapeutic effects in various solid tumors. However, for pancreatic cancer, known as the "king of cancer", immunotherapy has been ineffective. On August 4, Professor Yu Xianjun, Dean of the Cancer Hospital Affiliated to Fudan University, and Shi Si, Associate Professor of Pancreatic Surgery released a research achievement, which first found the key role of cysteine rich protein 1 in shaping the immunosuppressive microenvironment of pancreatic cancer, filled the gap in the research field of immunosuppressive microenvironment of pancreatic cancer, and provided a theoretical basis for precise immunotherapy of pancreatic cancer patients. Ductal adenocarcinoma of the pancreas is the main type of pancreatic cancer, accounting for about 90% of all pancreatic cancer. Due to its high malignancy and poor treatment effectiveness, pancreatic ductal adenocarcinoma has always been one of the most malignant tumors. In recent years, the level of surgical techniques and comprehensive treatment has been achieved

A 14-year-old girl suffers from a rare eye disease and receives support from a public welfare fund. Symptoms of "I haven't looked in the mirror for a long time" | Patient | Public welfare
A 14-year-old girl suffers from a rare eye disease and receives support from a public welfare fund. Symptoms of "I haven't looked in the mirror for a long time" | Patient | Public welfare

A 14-year-old girl has been experiencing symptoms such as protruding pupils, incomplete eye closure, corneal injury, restricted eye movement, and overall fatigue for several years. The physical discomfort and facial abnormalities caused by eye diseases have made her increasingly reticent, and her temperament is vastly different from before. At the Ophthalmology Department of the Ninth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, the pupil has been diagnosed with a rare thyroid ophthalmopathy combined with myasthenia gravis, which requires prompt treatment. However, considering the young age of the pupil, conventional hormone and radiation therapy cannot be used. Therefore, Zhou Huifang, Deputy Director of Ophthalmology and thyroid ophthalmology expert, has developed a targeted drug combined with surgical treatment plan for it, and targeted drug treatment will be performed first. Three months ago, I was hospitalized for one week with mydriasis and received intravenous targeted drug treatment. Afterwards, I went home for observation and followed up on time

The municipal eye disease prevention and treatment center launched the dry eye diagnosis and treatment studio, and the incidence rate of dry eye in China is about 21% to 30% of the meibomian gland | dry eye | eye disease
The municipal eye disease prevention and treatment center launched the dry eye diagnosis and treatment studio, and the incidence rate of dry eye in China is about 21% to 30% of the meibomian gland | dry eye | eye disease

According to the Statistics of Chinese Dry Eye Expert Consensus, the incidence rate of dry eye in China is about 21%~30%, and it is estimated that there are at least 300 million patients nationwide. The Dry Eye Diagnosis and Treatment Studio of Shanghai Eye Disease Prevention and Treatment Center was officially launched today. In the future, the studio will continuously improve the dry eye diagnosis and treatment standards, and form standardized diagnosis and treatment concepts and service models. Suitable technologies will be promoted to the community, allowing residents to enjoy convenient dry eye diagnosis and treatment services at their doorstep. Executive Dean and Party Secretary Gao Wei stated that this is also one of the livelihood service measures recently launched by the hospital around high-quality development and meeting the needs of the people. It is reported that dry eye syndrome is a chronic ocular surface disease caused by multiple factors. The instability of the tear film or imbalance of the ocular surface microenvironment caused by abnormal quality, quantity, and dynamics of tears can be accompanied by ocular surface inflammatory reactions, tissue damage, and nerve abnormalities, resulting in various discomforts in the eyes

The Ninth Hospital has taken the lead in formulating the world's first consensus on core indicators for clinical evaluation of dental implants, which has been officially published in clinical practice
The Ninth Hospital has taken the lead in formulating the world's first consensus on core indicators for clinical evaluation of dental implants, which has been officially published in clinical practice

The International Dental Implant Consensus Report, jointly written by the Ninth People's Hospital affiliated with Shanghai Jiao Tong University School of Medicine and renowned universities in the field of dentistry such as Harvard University, University of Zurich, University of Gothenburg, Columbia University, and University of Frankfurt, has recently been jointly published in top journals in the field of dentistry, including Clinical Periodontology and Clinical Dental Implant Research. This consensus has for the first time established an internationally unified core set of indicators for evaluating the clinical effectiveness of dental implants, covering the five key areas of the field of dental implants. It is of milestone significance for carrying out standardized clinical diagnosis, treatment, and research on dental implants. The core evaluation indicators determined by this consensus will become an important benchmark for scholars in the field of dental implants worldwide to conduct high-quality research. The consensus is composed of 8 top international experts in the field of oral implantation

Recently, autologous hematopoietic stem cell therapy was completed in Shanghai, and British girls born in the 1990s have suffered from multiple relapses of blood diseases, including stem cells, peripheral blood, and diseases
Recently, autologous hematopoietic stem cell therapy was completed in Shanghai, and British girls born in the 1990s have suffered from multiple relapses of blood diseases, including stem cells, peripheral blood, and diseases

Recently, Catherine, a British girl born in the 1990s, received autologous peripheral blood hematopoietic stem cell transfusion at the Cancer Center of Shanghai Jiahui International Hospital, and was successfully discharged from the warehouse. She is now on her way back to China after being discharged from the hospital. She is also the first patient at Shanghai Jiahui International Hospital to complete relevant treatments. In 2019, Catherine was diagnosed with Hodgkin's lymphoma in the UK, and after treatment, the disease completely improved. During her work and life in China in 2021, she went to seek medical attention due to multiple enlarged lymph nodes. Pathological biopsy confirmed a recurrence of Hodgkin's lymphoma, and through combined targeted drug treatment, her condition was temporarily under control. Last year in the second half of the year, when the disease recurred, the girl began to use immunotherapy combined with targeted drugs for treatment. Expert evaluation suggests that for young patients with hematological tumors, the risk of recurrence is high and treatment difficulty is increasing in the future. Autologous hematopoietic stem cell therapy is recommended