Exploration of the MSI landscape in Chinese pan-cancer patient by Next-Generation Sequencing.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e14576-e14576
Author(s):  
Xinlu Liu ◽  
Jiasheng Xu ◽  
Jian Sun ◽  
Deng Wei ◽  
Xinsheng Zhang ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Correlation Analysis ◽  
Cancer Patients ◽  
Cancer Type ◽  
Multiple Tumor ◽  
Treatment Plans ◽  
Cancer Types ◽  
Chinese Cancer Patients ◽  
Colorectal Cancer Patients ◽  
Pan Cancer

e14576 Background: Clinically, MSI had been used as an important molecular marker for the prognosis of colorectal cancer and other solid tumors and the formulation of adjuvant treatment plans, and it had been used to assist in the screening of Lynch syndrome. However, there were currently few reports on the incidence of MSI-H in Chinese pan-cancer patients. This study described the occurrence of MSI in a large multi-center pan-cancer cohort in China, and explored the correlation between MSI and patients' TMB, age, PD-L1 expression and other indicators. Methods: The study included 8361 patients with 8 cancer types from multiple tumor centers. Use immunohistochemistry to detect the expression of MMR protein (MLH1, MSH2, MSH6 and PMS2) in patients with various cancer types to determine the MSI status and detect the expression of PD-L1 in patients. Through NGS technology, 831 genes of 8361 Chinese cancer patients were sequenced and the tumor mutation load of the patients was calculated. The MSI mutations of patients in 8 cancer types were analyzed and the correlation between MSI mutations of patients and the patient's age, TMB and PD-L1 expression was analyzed. Results: The test results showed that MSI patients accounted for 1.66% of pan-cancers. Among them, MSI-H patients accounted for the highest proportion in intestinal cancer, reaching 7.2%. The correlation analysis between MSI and TMB was performed on patients of various cancer types. The results showed that: in each cancer type, MSI-H patients had TMB greater than 10, and 26.83% of MSI-H patients had TMB greater than 100 in colorectal cancer patients. The result of correlation analysis showed that there was no significant correlation between the patient's age and the risk of MSI mutation ( P> 0.05). In addition to PAAD and LUAD, the expression of PD-L1 in MSI-H patients was higher than that in MSS patients in other cancer types( P< 0.05). The correlation analysis between PD-L1 expression and TMB in patients found that in colorectal cancer, the higher the expression of PD-L1, the higher the patient's TMB ( P< 0.05). Conclusions: In this study, we explored the incidence of MSI-H in pan-cancer patients in China and found that the TMB was greater than 10 in patients with MSI-H. Compared with MSS patients, MSI-H patients have higher PD-L1 expression, and the higher the PD-L1 expression in colorectal cancer, the higher the TMB value of patients.

The prevalence of CDK12 alterations in Chinese cancer patients and the association with tumor mutation burden(TMB) and survival.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e13663-e13663
Author(s):  
Ke Li ◽  
Xi Guo ◽  
Yunhua Mao ◽  
Mengmei Yang ◽  
Mengli Huang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Molecular Subtype ◽  
Prostate Adenocarcinoma ◽  
Chinese Patients ◽  
Cyclin Dependent Kinase ◽  
Poor Prognostic Factor ◽  
Cancer Types ◽  
Chinese Cancer Patients ◽  
Pan Cancer

e13663 Background: Cyclin-dependent kinase 12 (CDK12) is a cyclin-dependent kinase that regulates transcription and RNA splicing, thereby modulating multiple cellular processes. It has been suggested that CDK12 loss-of-function mutations lead to a higher neoantigen burden and favorable responses to PD-1 inhibitors in advanced prostate cancer. Given this potentially actionable molecular subtype, we sought to determine the prevalence of CDK12 alterations in Chinese cancer patients and the association with TMB and overall survival(OS). Methods: The prevalence of CDK12 alterations were queried in 3D Medicines database with 15,745 Chinese cancer patients involved. Whole-exome sequencing data of 464 patients with prostate adenocarcinoma(PRAD) from the Cancer Genome Altas (TCGA) were downloaded to explore the association between CDK12 gene alteration and OS. And the association with TMB were analyzed in a cohort of 731 patients with various cancer types published by Memorial Sloan Kettering (MSKCC) (Samstein et al., Nature Genetics, 2019). Results: Any CDK12 and known or likely deleterious CDK12 mutations were identified in 598(3.8%) and 98(0.62%) patients, respectively. Across all cancer types, prostate adenocarcinoma(PRAD) was found to have the highest frequency of deleterious mutations(8.75%, 23/263), followed by breast cancer (4.97%, 25/503). Mutations were also detected in multiple cancer types including bladder cancer, ovarian cancer, lung cancer, colorectal cancer and so on with a frequency of less than 1%. CDK12 mutations were associated with shorter OS (HR = 15.25; 95% CI, 2.88-80.73; p < 0.001) in TCGA PRAD and cholangiocarcinoma datasets, which was not seen in other cancer types. Patients harboring CDK12 mutation had a significant higher TMB(p < 0.001) in the pan-cancer study of publicly-available cohort from MSKCC. Conclusions: CDK12 alterations existed across tumor types in Chinese patients with relatively high frequencies detected in PRAD and breast cancer and represent extremely rare events in multiple cancers. CDK12 mutation was a poor prognostic factor in PRAD and cholangiocarcinoma. In a pan cancer analysis patients with CDK12 mutation tended to have a significant higher TMB and may benefit from PD-1/L1 blockade immunotherapy.

Assessing adherence to the American College of Chest Physicians’ (ACCP) recommendations for thromboprophylaxis in hospitalized cancer patients

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 9047-9047
Author(s):  
A. N. Amin ◽  
S. A. Stemkowski ◽  
J. Lin ◽  
G. Yang
Keyword(s):  
Colorectal Cancer ◽  
At Risk ◽  
Cancer Patients ◽  
Significant Risk ◽  
Minimum Length ◽  
Cancer Type ◽  
Specific Recommendation ◽  
Inclusion Criteria ◽  
Vte Prophylaxis ◽  
Cancer Types

9047 Background: This study evaluates whether clinicians are providing appropriate VTE prophylaxis to at-risk surgical and non- surgical cancer patients in accordance with ACCP guidelines. Methods: Premier's inpatient administrative data were used to assess VTE prophylaxis rates in fourteen cancer types. Patients age 40 or older, with a minimum length of stay of six days, and no contraindications for anti-coagulation were included in the study. Two rates were determined; the rate of discharges receiving any level of anticoagulation and the rate of patients receiving appropriate prophylaxis by comparing daily use of anti-coagulants and compression devices, dosage, and prophylaxis duration with ACCP recommendations. The 6th guidelines were used due to their release prior to the study period. Rates based on the 7th guidelines were calculated for the same patient cohort to assess how the revised guidelines affect our findings. Trends were assessed by comparing prophylaxis rates by quarter. Results: 72,391 discharges from 225 hospitals between January 2002 and September 2005 met the inclusion criteria. 29% of all at-risk cancer discharges received the recommended prophylaxis regimen. Rates varied by cancer type ranging from 18.7% in prostate to 36.3% in colorectal cancer discharges. 55% did not receive any anti-coagulation prophylaxis, 9.5% received insufficient dosage and 5.8% did not receive prophylaxis for the appropriate duration. The appropriate VTE prophylaxis rate is higher for surgical cancer than for non-surgical cancer discharges (32.3% vs. 27.7%). Trends suggest a slight increase in appropriate prophylaxis rates for all types of cancer discharges. Appropriate prophylaxis rates based on 7th guidelines are lower than rates based on the 6th guidelines due to the more specific recommendation in the 7th guidelines. Conclusions: Cancer patients are known to have significant risk for VTE, yet VTE prophylaxis for at-risk non-surgical cancer patients in hospitals is not optimal. Rates for surgical cancer patients were only slightly higher. Using the 7th recommendations results in lower prophylaxis rates. More effort is required to increase awareness of the ACCP recommendations for thromboprophylaxis in cancer patients. No significant financial relationships to disclose.

Exploration of the TMB and hypermutation landscape in Chinese pan-cancer patient by next-generation sequencing.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e14575-e14575
Author(s):  
Shuo Wang ◽  
Jiasheng Xu ◽  
Jian Sun ◽  
Deng Wei ◽  
Xinsheng Zhang ◽  
...  
Keyword(s):  
Cancer Patient ◽  
Cancer Patients ◽  
Age And Gender ◽  
Tumor Mutation Burden ◽  
Mutation Burden ◽  
Cancer Types ◽  
And Gender ◽  
Chinese Cancer Patients ◽  
Pan Cancer ◽  
Generation Sequencing

e14575 Background: Among a variety of malignant tumors, the level of the patient's TMB was currently an important criterion for clinical judgment whether to adopt immunotherapy. Hypermutation could produce many nearby mutation sites at the same time, which seriously damages genetic material and may cause cancer. Therefore, performing TMB detection on cancer patients and understanding the occurrence of hypermutation in pan-cancer patients will help clinical researchers to further understand the disease characteristics of cancer patients and helped the choice of treatment methods. Previously, TMB and Hypermutation had been tested and studied in pan-cancer patients in the United States and Europe, but rare research was reported in China. In this study, we explored the TMB and hypermutation landscape in Chinese pan-cancer patient by next-generation sequencing. Methods: A total of 8,361 cancer patients from multiple cancer hospitals and research centers in China were included in the study. We sequenced 8,361 Chinese cancer patients from 8 cancer types using the oncopanscan product of Genetron Health Co., Ltd. and calculated the tumor mutation burden of the patients. We separately analyzed the tumor mutation burden of patients in 8 cancer types and analyzed the relationship between the occurrence of hypermutation and the patient's age and gender. Results: The results showed that in pan-cancer, hypermutation patients accounted for 16.97%, and ultrahypermutation patients accounted for 0.78%. Among them, patients with lung cancer have the highest proportion of hypermutation, reaching 27.72%, and patients with colorectal cancer have the highest proportion of ultrahypermutation, reaching 2.86%. Correlation analysis between TMB and age and gender was carried out on 8336 patients. The results showed that in the patients with intrahepatic bile duct cancer, the proportion of men and women was the same. Among the other cancer types, hypermutation patients were more male, and the proportion of men with liver cancer was the largest, with 90 percent. We further explored the correlation between the TMB of pan-cancer patients and the patient’s age, and found that in gastric cancer, liver cancer, and melanoma, the older patients have higher TMB; however, the younger the patients in brain cancer, the higher the TMB ( P<0.05). Conclusions: In this study, we explored the TMB and hypermutation landscape in Chinese pan-Cancer patient for the first time. We found that among Chinese cancer patients, lung cancer patients have the highest proportion of hypermutation. In a variety of cancers, hypermutation patients account for a higher proportion of men, and the older the patient, the higher the TMB.

scholarly journals Building personalized treatment plans for early-stage colorectal cancer patients

Oncotarget ◽  
2017 ◽  
Vol 8 (8) ◽  
pp. 13805-13817 ◽  
Author(s):  
Hung-Hsin Lin ◽  
Nien-Chih Wei ◽  
Teh-Ying Chou ◽  
Chun-Chi Lin ◽  
Yuan-Tsu Lan ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cancer Patients ◽  
Early Stage ◽  
Personalized Treatment ◽  
Treatment Plans ◽  
Colorectal Cancer Patients

scholarly journals Frequency of Morphologic Prognostic Factors in Surgically Treated Colorectal Cancer

2014 ◽  
Vol 14 (1) ◽  
pp. 3-10 ◽  
Author(s):  
Inese Drike ◽  
Ilze Strumfa ◽  
Andrejs Vanags ◽  
Janis Gardovskis
Keyword(s):  
Colorectal Cancer ◽  
Prognostic Factors ◽  
Cancer Patients ◽  
Lymphatic Invasion ◽  
World Health ◽  
Cancer Type ◽  
Tumour Spread ◽  
Incidence And Mortality ◽  
Local Tumour ◽  
Colorectal Cancer Patients

Summary Introduction. Colorectal cancer is one of the most frequent malignant tumours worldwide. In Latvia, the incidence and mortality from colorectal cancer has increased over the past five years. Surgery is the mainstay of colorectal cancer treatment. However, the prognosis of an individual patient after the operation depends on many factors. Here, we report the prognostically important morphologic factors in potentially radically operated colorectal cancer patients in order to create the “morphologic prognostic portrait” - the basic morphologic characteristics of colorectal cancer in Latvian patients. Such data could be helpful in prognostic estimates. Aim of the study was to describe the local tumour spread by pT, to evaluate the occurrence of certain morphologic prognostic factors and to assess lymph node involvement in potentially radically operated colorectal cancer patients. Material and methods. In a retrospective study, 173 consecutive patients who underwent a potentially radical operation in a single university hospital within the year 2012 were identified by archive search. The pathology reports that have been created by protocol approach and diagnostic microscopy slides were reanalysed. Tumour morphology and pTN parameters were assessed according to the World Health Organization and the American Joint Committee on Cancer classifications. Results. The study included 98 women (56.6%) and 75 men (43.4%). The mean age of patients was 68.5 years [95% confidence interval: 66.9 – 70.1]. Only 4.6% [2.4 – 8.9] of patients were younger than 50 years. The most frequent histological tumour types were colorectal adenocarcinoma in 86.7% [80.8 – 90.9] patients and mucinous carcinoma in 9.2% [5.7 – 14.5] of patients. Evaluating the pT parameter, pT3 was found in 43.2% [36.1 – 50.6] and pT4 in 39.8% [32.8 – 47.2] of cases. Lymphatic invasion was found in 35.1% [25.3 – 46.2] of pT3 and 75.4% [64.0 – 84.0] of pT4 cases; p < 0.001. Perineural cancer invasion in pT3 and pT4 tumours was found in 29.9% [20.8 – 40.9] and 69.6% [57.9 – 79.2], respectively; p < 0.001. Conclusions. Colorectal cancer affects both genders with equal frequency. The tumour is mostly diagnosed after the age of 60 years. Adenocarcinoma is the predominant colorectal cancer type in radically operated patients. Perineural and lymphatic invasion in pT4 tumours is statistically significantly more frequent than in less advanced tumours and thus may be pathogenetically linked to wide local tumour spread.

scholarly journals Pan-Cancer Integrative Analysis of Whole-Genome De novo Somatic Point Mutations Reveals 17 Cancer Types

2021 ◽  
Author(s):  
Amirreza Kazemi ◽  
Amin Ghareyazi ◽  
Kimia Hamidieh ◽  
Hamed Dashti ◽  
Maedeh Tahaei ◽  
...  
Keyword(s):  
Cancer Patients ◽  
Molecular Mechanisms ◽  
High Throughput Sequencing ◽  
Specific Treatment ◽  
Cancer Drug ◽  
Cancer Type ◽  
Cancer Subtypes ◽  
Genotypic Analysis ◽  
Cancer Types ◽  
Pan Cancer

The advent of high throughput sequencing has enabled researchers to systematically evaluate the genetic variations in cancer, resulting in identifying many cancer-associated genes. Although cancers in the same tissue are widely categorized in the same group, they demonstrate many differences concerning their mutational profiles. Hence there is no &ldquo;silver bullet&rdquo; for the treatment of a cancer type. This reveals the importance of developing a pipeline to identify cancer-associated genes accurately and re-classify patients with similar mutational profiles. Classification of cancer patients with similar mutational profiles may help discover subtypes of cancer patients who might benefit from specific treatment types. In this study, we propose a new machine learning pipeline to identify protein-coding genes mutated in a significant portion of samples to identify cancer subtypes. We applied our pipeline to 12270 samples collected from the International Cancer Genome Consortium (ICGC), covering 19 cancer types. Here we identified 17 different cancer subtypes. Comprehensive phenotypic and genotypic analysis indicates distinguishable properties, including unique cancer-related signaling pathways, in which, for most of them, targeted treatment options are currently available. This new subtyping approach offers a novel opportunity for cancer drug development based on the mutational profile of patients. We also comprehensive study the causes of mutations among samples in each subtype by mining the mutational signatures, which provides important insight into their active molecular mechanisms. Some of the pathways we identified in most subtypes, including the cell cycle and the Axon guidance pathways, are frequently observed in cancer disease. Interestingly, we also identified several mutated genes and different rates of mutation in multiple cancer subtypes. In addition, our study on &ldquo;gene-motif&rdquo; suggests the importance of considering both the context of the mutations and mutational processes in identifying cancer-associated genes. The source codes for our proposed clustering pipeline and analysis are publicly available at: https://github.com/bcb-sut/Pan-Cancer.

Incidental Versus Symptomatic Pulmonary Embolism in Cancer Patients: A Multivariate Analysis of Recurrent VTE and Mortality.

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 2257-2257 ◽  
Author(s):  
Kathy Deng ◽  
Rekha Parameswaran ◽  
Benjamin P Soff ◽  
Gerald A. Soff
Keyword(s):  
Colorectal Cancer ◽  
Cancer Patients ◽  
Cancer Staging ◽  
Cancer Type ◽  
Data Set ◽  
Anatomic Location ◽  
Initial Location ◽  
All Cause Mortality ◽  
Cancer Types ◽  
Recurrent Vte

Abstract Abstract 2257 Venous thromboembolism (VTE) is a major cause of morbidity and mortality in cancer. In the context of frequent high-resolution imaging, pulmonary emboli (PE) are frequently identified incidental to other indications for imaging. Several key questions need answers. In cancer, are incidentally identified and symptomatic PEs of comparable clinical importance regarding risk of recurrent VTE and death? Can we identify a subgroup of patients with incidentally identified PEs for whom the risk of recurrent VTE is sufficiently low that long-term anticoagulation may not be necessary? Several recent studies suggest that incidental PE may result in comparable rates of recurrent VTE and death as symptomatic PE. However, those studies did not control for cancer type and anatomic distribution of the initial PE. We now report a comprehensive data set on PE in cancer, derived from MSKCC. All PE in a 2-year period (2008–9) were reviewed, with 2-year follow-up. We evaluated the cases for all cause mortality with time, as well as all recurrent VTE. There were 755 initial symptomatic PE with 122 recurrent VTE events and 574 initial incidental PEs with 124 recurrent VTE. 43.2% of all PEs were identified incidentally. The percent of total PEs that were identified incidentally varied markedly with different cancer types, pancreas (70.7%), colorectal (61.4%), hematologic (33.3%), gastro-esophageal (37.7%), lung (32.8%), breast (15.1%), gynecological (30.0%), brain (5.0%). Brain tumor patients less frequently undergo comprehensive body imaging for cancer staging, and therefore, asymptomatic PEs may be less likely identified incidentally. Because of the well-recognized differences in rates of recurrent VTE and mortality in different cancer types, differences in the percent of incidental PEs supports the necessity of considering cancer type in outcome analysis. The overall hazard ratios of death and recurrent VTE were highest in the first month after the initial PE, gradually declining with time. The cumulative rates of all cause mortality was higher for symptomatic PE in the initial 2 months, but equalized by 12 months. (All cause mortality, symptomatic PE: 1 month: 15%, 2 month: 24%, 6 month: 40%, 12 month: 53%. Incidental PE: 1 month: 6%, 2 month: 12%, 6 month: 30%, 12 month: 47%). Cumulative rates of recurrent VTE were similar in both cohorts. (Symptomatic PE: 3 month: 11.0%, 6 month: 13.6%, 12 month: 16.0%. Incidental PE: 3 month: 11.7%, 6 month: 17.1%, 12 month: 21.4%). For most major cancer types, early (1-month) mortality and 12-month recurrent VTE rates were similar regardless of the incidental versus symptomatic nature of the initial PE. However, for colorectal cancer, the 1-month mortality for symptomatic PE was 14.3% (8 of 56), but only 3.4% (3 of 89) for incidental PE, and the 12-month recurrent VTE rate was 17.9% for symptomatic PE and 5.6% for incidental PE. The anatomic location of the initial PE also evaluated. Segmental arteries were the most common initial location of symptomatic (45%) and incidental (47%) PE. Importantly, after an initial incidental PE, the risk of recurrent VTE was consistent, regardless of the initial anatomic location. For each category; main plus saddle, lobar, segmental, and subsegmental, the recurrent VTE rates were between 20 – 25%. The fact that a cancer patient exhibits a PE predicts recurrent VTE, with less relevance to the anatomic location of the initial event. Conclusions: In our institution, 43.2% of PEs in cancer patients were identified incidentally, by imaging studies performed for cancer staging, or evaluation of complaints not typically associated with PE. All cause mortality was twice as high in the first two months after a symptomatic PE as an incidental PE, but by the third month, the monthly rates became equivalent. The hazard ratio of recurrent VTE was similar between the symptomatic PE and incidental PE cohorts, including subgroups. A possible exception is in colorectal cancer, in which the 1- month mortality and 12-month recurrent VTE rates were higher for symptomatic PE. However, due to the retrospective nature of this study, and the multiple parameters considered, that observation needs confirmation. As even “small” subsegmental PEs are associated with recurrent VTE rates comparable to large proximal PEs, our data do not suggest that there are any subgroups for which anticoagulation is not justified. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Capture of Viable Circulating Tumor Cells in the Liver of Colorectal Cancer Patients

2013 ◽  
Vol 59 (9) ◽  
pp. 1384-1392 ◽  
Author(s):  
Eric Denève ◽  
Sabine Riethdorf ◽  
Jeanne Ramos ◽  
David Nocca ◽  
Amandine Coffy ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cancer Patients ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Peripheral Blood ◽  
Tumor Resection ◽  
Reference Method ◽  
Biological Properties ◽  
Cancer Types ◽  
Colorectal Cancer Patients

BACKGROUND The incidence and number of circulating tumor cells (CTCs) in the peripheral blood of colorectal cancer patients are lower than in other cancer types, which may point to a particular biology of colorectal cancer affecting CTC detection. METHODS We detected CTCs in the peripheral and mesenteric blood of colorectal cancer patients by use of 2 independent technologies on the basis of different biological properties of colon cancer cells. Seventy-five patients diagnosed with localized (M0, n = 60) and metastatic (M1, n = 15) colorectal cancer were included. Peripheral and mesenteric blood samples were collected before tumor resection. We performed CTC enumeration with an EpCAM-independent enrichment method followed by the Epispot assay that detected only viable CK19-releasing CTCs. In parallel, we used the FDA-cleared EpCAM-dependent CellSearch® as the reference method. RESULTS The enumeration of CK19-releasing cells by the CK19-Epispot assay revealed viable CTCs in 27 of 41 (65.9%) and 41 of 74 (55.4%) (P = 0.04) patients in mesenteric and peripheral blood, respectively, whereas CellSearch detected CTCs in 19 of 34 (55.9%) and 20 of 69 (29.0%) (P = 0.0046) patients. In mesenteric blood, medians of 4 (range 0–247) and 2.7 CTCs (range 0–286) were found with Epispot and CellSearch (P = 0.2), respectively, whereas in peripheral blood, Epispot and CellSearch detected a median of 1.2 (range 0–92) and 0 CTCs (range 0–147) (P = 0.002). CONCLUSIONS A considerable portion of viable CTCs detectable by the Epispot assay are trapped in the liver as the first filter organ in CRC patients.

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