In the March 08 issue of Zealotific Daily, we deciphered 9 articles focusing on: metastatic colorectal cancer, diagnostic markers, liver transplantation, ketogenic diet, breast cancer, esophageal cancer, adjuvant chemotherapy, E. coli, mitochondria, microsatellite stabilization.
<h1>Sun Yat-sen University: A novel diagnostic marker for colorectal cancer</h1>
Genome Medicine——[10.675]
(1) Plasma tDR expression profiles of 105 colorectal cancer patients and 90 healthy controls were compared by small RNA sequencing; (2) the expression of 5′-tRF-GlyGCC in the plasma of colorectal cancer patients was significantly increased by qPCR verification; (3) the AUC based on 5′-tRF-GlyGCC distinguishing colorectal cancer from healthy control was 0.882, and the AUC of colorectal cancer and healthy control combined with 5′-tRF-GlyGCC and carcinoembryonic antigen could be increased to 0.926; (4) In colorectal cancer cell lines and mouse models inoculated colorectal cancer cells, the 5′-tRF-GlyGCC level was significantly elevated; (5) the increase in expression of 5′-tRF-GlyGCC was dependent on the upregulation of ALKBH3, a tRNA demethylase.
【Editor-in-Chief's Comments】
Small TRNAs (tDRs) derived from tRNA are widely distributed in human tissues, including blood and urine, and play an important role in cancer progression. A new study published in Genome Medicine by Hongsheng Wang's team, Jiexin Li's team at Sun Yat-sen University, and Huanliang Liu's team from the Sixth Affiliated Hospital of Sun Yat-sen University found that the expression of a specific tDR- 5′-tRF-GlyGCC was significantly elevated in the plasma, colorectal cancer cell lines, and colorectal cancer mouse models of colorectal cancer patients. 5′-tRF-GlyGCC alone, or in combination with 5′-tRF-GlyGCC and carcinoembryonic antigen, can accurately distinguish colorectal cancer patients from healthy controls. The findings suggest that 5′-tRF-GlyGCC may be used as a novel biomarker for the diagnosis of colorectal cancer. （@szx）
【Original information】
5′-tRF-GlyGCC: a tRNA-derived small RNA as a novel biomarker for colorectal cancer diagnosis
2021-02-09, doi: 10.1186/s13073-021-00833-x
<h1>Sun Yat-sen University: A new marker predicting the prognosis of adjuvant chemotherapy for colorectal cancer</h1>
Journal for ImmunoTherapy of Cancer——[9.913]
(1) CMTM6 expression in colorectal cancer was higher than in normal colonic tissue, and CMTM6 expression in advanced colorectal cancer was lower than in early tumor tissue; (2) high expression of CMTM6 was associated with lower tumor stage, more CD4+/CD8+ tumor infiltrating lymphocytes, and better colorectal cancer prognosis; (3) positive PD-L1 expression in tumor matrix (rather than tumor cells) was associated with increased density and better prognosis of CD4+ tumor infiltrating lymphocytes; (4) in patients receiving adjuvant chemotherapy, According to the co-expression of CMTM6 and PD-L1, patients can be divided into three groups: the risk of progression and death is low, moderate, and high, and patients with high expression of CMTM6 and PD-L1 have the longest survival.
CMTM6 is a regulator of PD-L1, expressed in a variety of tumors, regulating the tumor immune microenvironment. A new study published by Ranyi Liu's team at Sun Yat-sen University in the Journal for ImmunoTherapy of Cancer, which included 156 colorectal cancer patients who received adjuvant chemotherapy and 77 who did not receive chemotherapy, found that high expression of CMTM6 and PD-L1 in tumor tissue was associated with more lymphocyte tumor infiltration and better prognosis. （@szx）
CMTM6 and PD-L1 coexpression is associated with an active immune microenvironment and a favorable prognosis in colorectal cancer
2021-02-12, doi: 10.1136/jitc-2020-001638
<h1>JAMA: An article on the diagnosis and treatment of metastatic colorectal cancer (review</h1>).
JAMA——[45.54]
(1) Colonoscopy confirms primary colorectal cancer, biopsy confirms liver, lung, and lymphatic metastases, MRI, and PET can help identify metastases; (2) oxaliplatin or irinotecan-based chemotherapy is the first-line treatment for metastatic colorectal cancer; (3) 50% of patients are KRAS/NRAS/BRAF wild type, which can receive monoclonal antibody/fusion proteins targeting VEGF or EGFR and combined chemotherapy; (4) 35%-40% of patients are KRAS/NRAS mutant types, and there is no effective treatment; (5) 5%- 10% of patients have BRAF V600E mutant, with EGFR monoclonal antibodies and BRAF inhibitors, and (6) 5% of patients have microsatellite instability/mismatch repair defects, and immunotherapy can significantly prolong survival.
Colorectal cancer is the third largest tumor in the world, with more than 1.85 million people diagnosed with colorectal cancer and about 850,000 people dying from colorectal cancer each year. 20% of new colorectal cancers are metastatic colorectal cancers, while 25% of primary colorectal cancers are likely to develop metastatic colorectal cancers. Patients with metastatic colorectal cancer have a 5-year survival rate of less than 20%. A review article published at JAMA details the diagnosis of metastatic colorectal cancer and available treatments. （@szx）
Diagnosis and Treatment of Metastatic Colorectal Cancer: A Review
2021-02-16, doi: 10.1001/jama.2021.0106
<h1>Which populations are at high risk of colorectal and pancreatic cancer after liver transplantation? </h1>
Hepatology——[14.679]
(1) 98,679 adult liver transplant recipients were included, comparing the incidence of cancer in normal population data; (2) 866 liver transplant recipients with new malignant tumors of the gastrointestinal tract, 405 cases of colorectal cancer, and 216 cases of pancreatic cancer; (3) patients with primary sclerosing cholangitis (PSC), patients with non-alcoholic steatohepatitis (NASH) and hepatocellular carcinoma (HCC/CCA) patients over 50 years of age, and patients with alcoholic liver disease (ALD) and hepatocellular carcinoma/CCA in women over 50 years of age after liver transplantation. The cumulative incidence of colorectal cancer is highest; (4) Patients with PSC and HCC/CCA or NASH and HCC/CCA have the highest cumulative incidence of pancreatic cancer after liver transplantation, and the risk increases within 5 years of transplantation.
Patients with liver transplantation have a high incidence of gastrointestinal malignancies. A recently published study by Hepatology analyzed the incidence and development of gastrointestinal malignancies in 98,679 adult liver transplant recipients from 1997 to 2017 in order to assess the prevalence of all new gastrointestinal malignancies and to analyze the incidence and development of gastrointestinal malignancies in patients with sclerotic cholangitis, non-alcoholic steatohepatitis (NASH) and alcoholic liver disease (ALD) compared with those transplanted for other diseases, in order to assess the prevalence of all new gastrointestinal malignancies and to analyze the incidence and development of gastrointestinal malignancies in 98,679 adult liver transplant recipients from 1997 to 2017. A high-risk cohort of post-liver transplant colorectal and pancreatic cancer screening was identified. The results of this study may be used to guide screening for clinically relevant diseases. （@nana）
De novo Colorectal and Pancreatic Cancer in Liver Transplant Recipients: Identifying the Higher Risk Populations
2021-02-05, doi: 10.1002/hep.31731
<h1>Nature Sub-Journal: New Evidence for Colibactin-Producing E. Coli for Colorectal Cancer</h1>
Nature Communications——[12.121]
(1) pks+ E. coli expressing colibactin infected mouse colon organoids, producing mutant organoids that did not depend on Wnt signal growth; (2) mutations with colorectal cancer (CRC) cell characteristics: strong proliferation ability, Wnt independence and impaired differentiation; (3) typical chromosomal aberrations of mutant organoids exhibiting genomic instability; (4) mutant organoids producing genetic mutations associated with p53 signaling, such as miR-34a, Trp53 or miR-34 knockout experiments confirmed the functional interaction between the p53 and Wnt pathways; (5) larger chromosomal aberrations and aneuploidies are the basis for organoid transformation, consistent with chromosomal instabilities in the early stages of CRC.
In a mouse model of colorectal cancer (CRC), colibactin-producing pks + E. coli induce DNA double-strand breaks, mutations, and promote tumor development. It is unclear whether healthy primary colon epithelial cells respond in the same way to infection. A recently published study by Nature Communications, using mouse colonoids, demonstrated that pks+ E. coli can promote malignant transformation of colonic organoids in vitro, highlighting the correlation between the number of replication variants and the development of early colon cancer. （@nana）
Genomic aberrations after short-term exposure to colibactin-producing E. coli transform primary colon epithelial cells
2021-02-12, doi: 10.1038/s41467-021-21162-y
<h1>Microsatellites stabilize two molecular subtypes of colorectal cancer</h1>
Cancer Research——[9.727]
(1) Chr20q amplification is the most common copy number variant in colorectal cancer, present in 46% of colon cancer patients and 61% of rectal cancer patients, respectively; (2) Chr20q amplification is not present in MSI colorectal cancer patients; (3) MSS(MSS-A) colorectal cancer patients with Chr20q amplification have a longer recurrence-free survival period than MSS(MSS-N) colorectal cancer patients without Chr20q amplification; (4) (5) MSS-A and MSS-N tumors are associated with somatic mutations of different driver genes, p53 mutations are common in MSS-A, and KRAS and BRAF mutations are common in MSS-N.
About 15% of colorectal cancers are microsatellite unstable (MSI), which has better survival rates and is more sensitive to immunotherapy. Whether microsatellite-stabilized (MSS) colorectal cancer patients can be further divided into different subgroups is unclear. A new study published in Cancer Research found that MSS colorectal cancer can be divided into two different molecular subtypes, depending on whether or not it carries Chr20q amplification, which correspond to different prognosis, chromosomal stability, tumor microenvironment, and driver gene mutations. The findings suggest that further grouping of PATIENTS colorectal cancer patients can better develop precision treatment regimens. （@szx）
Chr20q amplification defines a distinct molecular subtype of microsatellite stable colorectal cancer
2021-02-22, doi: 10.1158/0008-5472.CAN-20-4009
<h1>Nature Reviews: Incidence, risk factors and prevention of esophageal cancer (review</h1>).
Nature Reviews Gastroenterology and Hepatology——[29.848]
(1) Esophageal squamous cell carcinoma (ESCC) is the most common subtype of esophageal cancer, while the incidence of esophageal adenocarcinoma (EAC) is higher in Western countries, and the incidence of EAC in men is higher but unexplained; (2) The main risk factors for EAC and Barrett's esophagus are gastroesophageal reflux disease, obesity and smoking, while alcohol consumption and smoking are risk factors for ESCC; (3) CRTC1, BARX1, GDF7 genes are associated with Barrett's esophagus and EAC; (4) Patients with EAC with a history of Barrett's esophagus had better clinical outcomes than patients with EAC without a history of Barrett's esophagus; (5) proton pump inhibitors, aspirin, statins, etc. may reduce the risk of EAC.
Esophageal cancer is a global disease, with nearly 600,000 patients diagnosed in 2018. A review article published in Nature Reviews Gastroenterology and Hepatology details the incidence, risk factors, environmental/genetic risk factors, prognosis, screening, and potential prevention of two subtypes of esophageal cancer—esophageal squamous cell carcinoma and esophageal adenocarcinoma. （@szx）
Global burden and epidemiology of Barrett oesophagus and oesophageal cancer
2021-02-18, doi: 10.1038/s41575-021-00419-3
<h1>Cell Sub-Journal: Metformin + restricted diet asparagine, or anti-cancer</h1>
Cell Metabolism——[21.567]
(1) Inhibition of electron transport chain (ETC) In addition to consuming intracellular aspartic acid, aspartate-derived asparagine is consumed, transcriptional activator 4 (ATF4) levels are increased, and mTOR complex I (mTORC1) activity is reduced; (2) exogenous asparagine can restore cell proliferation, ATF4 and mTORC1 activity, and mTORC1-dependent nucleotide synthesis with ETC inhibition, suggesting that asparagine can be linked to respiration with ATF4, mTORC1; (3) The combined effects of metformin (ETC inhibitors that restrict tumor asparagine synthesis) and asparaginase, or ETC inhibition and restriction of dietary asparagine intake, can effectively limit the growth of many tumors.
Mitochondrial respiration is essential for cell proliferation. In addition to producing ATP, respiration also produces biosynthetic precursors such as aspartic acid, which is an important substrate for nucleotide synthesis. Cell Metabolism recently published an article that found that asparagine in the environment is sufficient to restore tumor growth in the case of respiratory damage, and asparagine synthesis is the basic purpose of tumor mitochondrial respiration, which may be a therapeutic target. (@Love Choice)
Asparagine couples mitochondrial respiration to ATF4 activity and tumor growth
2021-02-19, doi: 10.1016/j.cmet.2021.02.001
<h1>The ketogenic diet may be beneficial for patients with radiation-stage breast cancer</h1>
Clinical Nutrition——[6.36]
(1) 59 women with early-stage breast cancer who received radiation therapy were included, of which 29 received a ketogenic diet (KD) and another 30 patients received a standard diet (SD) ;(2) Compared with SD, the KD group patients had significant improvements in emotional function, social function and sleep quality, and the KD group had fewer side effects of systemic therapy; (3) breast cancer symptoms in both groups were significantly worse, but the exacerbation in the KD group was not obvious; (4) the KD group had no damage to liver or kidney function and characterized metabolic health biomarkers, For example, γ-glutamyl transpeptidase, creatinine, triglycerides, insulin-like growth factor-1 and free triiodothyronine have been significantly improved.
The ketogenic diet (KD) has been proposed as a nutritional supplement for cancer patients, and it is important to understand the safety of the ketogenic diet during cancer treatment, clinical nutrition recently published an article that studied the effect of the ketogenic diet on the quality of life and blood parameters of women with early breast cancer receiving radiation therapy, and the results showed that the ketogenic diet during radiotherapy was safe for breast cancer patients and could improve the quality of life and metabolic health of patients. （@nana）
A ketogenic diet consumed during radiotherapy improves several aspects of quality of life and metabolic health in women with breast cancer
2021-01-26, doi: 10.1016/j.clnu.2021.01.023
Thanks to the creators of this issue of the daily: szx, nana, Wu Qin, Ze xinxin, Chen Binlin, Catalpa?
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