Hepatocellular carcinoma with ARID1A mutation is associated with higher TMB and poor survival.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e16667-e16667 ◽  
Author(s):  
Yaorong Peng ◽  
Bowen Gao ◽  
Zhenyu Zhou ◽  
Tingting Chen ◽  
Wenzhuan Xie ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cancer Patients ◽  
Gene Mutation ◽  
Sequencing Data ◽  
Coding Region ◽  
Poor Prognostic Factor ◽  
Synonymous Mutations ◽  
Significant Difference ◽  
Chinese Cohort ◽  
Pan Cancer

e16667 Background: Hepatocellular carcinoma (HCC) is a heterogeneous disease that lacks molecular predictors of response to available treatments. AT-rich interactive domain 1A (ARID1A), a SWI/SNF chromatin remodeling gene, is commonly mutated in human cancers and hypothesized to be a tumor suppressor gene. In recent years, immune checkpoint blockade immunotherapies (ICIs) are promising therapies for multiple cancers including HCC, and tumor mutation burden (TMB) was an important biomarker to predict the efficacy of ICIs. Besides, previous research reported that ARID1A deficiency was associated with mismatch repair (MMR) in cancer, and may cooperated with ICIs. Methods: Whole exome sequencing data of 10336 pan-cancer patients including 353 HCC patients was obtained from the Cancer Genome Altas (TCGA). Next generation sequencing (NGS) data of 15849 pan-cancer patients including 1926 HCC patients from Chinese clinical dataset were analyzed to explore the correlation between ARID1A gene mutation and TMB. TMB was defined as total number of somatic non-synonymous mutations in coding region. Prognostic data of 136 HCC patients were obtained from the MSK-IMPACT Clinical Sequencing Cohort (MSKCC). Results: In total, 8.62% (891/10336) of pan-cancer patients in TCGA harboring ARID1A mutation and 8.47% (3188/37628) in Chinese cohort, while mutant percentage of HCC was 9.35% (33/353) in TCGA, 9.03% (174/1926) in Chinese cohort, the alternation frequency of ARID1A in two cohorts was no significant difference (P = 0.3334). The medium TMB level of ARID1A mutant group was higher than wild-type group with significant difference both in Chinese pan-cancer and HCC (medium TMB level, P < 0.0001). Results of 18 kinds of ARID1A mutated tumors patients in TCGA cohort indicated that ARID1A mutation was an independent risk factor in liver cancer affecting overall survival (OS, HR 2.43, 95% IC 1.07-5.54, P = 0.0286). Besides, Kaplan-Meier analysis was performed on HCC patients in MSKCC cohort, ARID1A statue resulted in significantly shorter OS (median, 12.2 vs 21.43 months; HR 2.5; P = 0.0092). Conclusions: The results indicated that ARID1A gene mutation was a poor prognostic factor in hepatocellular carcinoma, and these mutational states were associated with higher TMB level, which might be a potential positive biomarker of immunotherapy.

A pan-cancer analysis of ARID1A as a potential biomarker for immune checkpoint therapy.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 3540-3540
Author(s):  
Dongyong Yang ◽  
Yuan Xu ◽  
Linlin Huang ◽  
Zhifeng Guo ◽  
Jimin Fan ◽  
...  
Keyword(s):  
Cancer Patients ◽  
Gene Mutation ◽  
Immune Checkpoint ◽  
Immune Checkpoint Blockade ◽  
Study Cohort ◽  
Tumor Type ◽  
Significant Difference ◽  
Chinese Cohort ◽  
Ngs Data ◽  
Pan Cancer

3540 Background: AT-rich interactive domain 1A (ARID1A), encoding a subunit of the BAF (SWI/SNF) chromatin remodeling complex, is correlated with the origination and progress of tumor. Previous research on ARID1A gene revealed that ARID1A deficiency was associated with mismatch repair (MMR) and higher tumor mutation burden (TMB) level in cancer, which might cooperate with immune checkpoint blockade therapy. Methods: Next generation sequencing (NGS) data of 10336 pan-cancer patients were obtained from the MSK-IMPACT Clinical Sequencing cohort (MSKCC). NGS data of 15849 pan-cancer patients from Chinese clinical dataset were analyzed to explore the association between ARID1A gene mutation and TMB. TMB was defined as total number of somatic non-synonymous mutations in coding region. 853 advanced NSCLC patients from two independent cohorts (OAK study cohort and POPLAR study cohort) were used to analyze the correlation between ARID1A alteration and the efficacy of immune checkpoint blockade immunotherapies (ICIs). Results: In total, 8.62% (891/10336) of pan-cancer patients in MSKCC harbored ARID1A mutation and 8.47% (3188/37628) in Chinese cohort. In MSKCC cohort, the highest ARID1A mutation frequency tumor type was endometrial cancer (31.64%, 69/218), bladder cancer (26.95%, 114/423) and hepatobiliary cancer (17.18%, 61/355) come in second and third, respectively. While in Chinese cohort, the top three ARID1A mutation frequency tumor types were endometrial cancer (39.29%, 88/224), gastric carcinoma (17.80%, 318/1787) and urothelial carcinoma (17.18%, 83/483), respectively. ARID1A gene mutation was also associated with higher TMB in the Chinese pan-cancer cohort (P < 0.0001). The highest medium TMB level of ARID1A mutation tumor type was Urothelial carcinoma with 18.63 Muts/Mb (n = 65). In addition, the TMB level and prognositic analysis were performed on patients in two independent NSCLC cohorts with ICIs, TMB level of ARID1A mutant group was higher than wild-type group with significant difference (P < 0.0001). The overall survival (OS) of ARID1A mutation group were significantly shorter than wild-type group (OS, median, 6.80 vs 10.28 months; HR, 1.47; P = 0.0474), and a decreasing trend on progression-free survival (PFS) without significant difference (median, 1.46 vs 2.99 months; HR, 1.27; P = 0.1584). Conclusions: The results indicated that ARID1A gene mutation was associated with a higher TMB level in Chinese pan-cancer patients, and patients harboring these genes mutations might easily benefit from ICIs.

A pan-cancer study on characteristic of CDK4/6 amplification between Chinese and Western patients.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e15074-e15074
Author(s):  
Yamin Zhang ◽  
Zilin Cui ◽  
Rui Shi ◽  
Xiaolong Liu ◽  
Yang Li ◽  
...  
Keyword(s):  
Soft Tissue ◽  
Liver Cancer ◽  
Soft Tissue Sarcoma ◽  
Lung Adenocarcinoma ◽  
Ovarian Carcinoma ◽  
Cancer Patients ◽  
Stomach Carcinoma ◽  
Chinese Cohort ◽  
Cancer Types ◽  
Pan Cancer

e15074 Background: CDK4/6 kinases associate with cyclin D proteins during transition from G1 to S phase of the cell cycle. Amplification of CDK4/6 may elicit the activity of cyclin D, which hyperphosphorylates RB, ultimately leading to uncontrolled cell proliferation. Currently, three CDK4/6 inhibitors are used in breast cancer, ovarian cancer and sarcoma. Herein, we investigate the prevalence of CDK4/6 amplification in Chinese and Western cancer patients, hope to find more cancer subtypes with CDK4/6 amplification. Methods: Next-generation sequencing data and clinical data were collected from 10828 TCGA pan-cancer patients (Western cohort). A 539-gene panel targeted sequencing assay was performed on FFPE tumor samples from 4181 Chinese pan-cancer patients (Chinese cohort). CDK4 and CDK6 amplification were calculated on the two cohorts following the same criteria. Results: In total, 182 (4.4%) of the 4181 Chinese patients and 529 (4.9%) of the 10828 Western patients had CDK4 amplification, 133 (3.2%) of the 4181 Chinese patients and 475 (4.4%) of the 10828 Western patients had CDK6 amplification. In Western cohort, the top 5 CDK4 amplification-associated cancer types were sarcoma, glioblastoma multiforme, lung adenocarcinoma, ovarian carcinoma, and adrenocortical carcinoma, and the top 5 CDK6 amplification-associated cancer types were esophageal carcinoma, ovarian carcinoma, lung squamous cell carcinoma, stomach adenocarcinoma, sarcoma. In Chinese cohort, the top 5 CDK4 amplification-associated cancer types were lung adenocarcinoma, melanoma, sarcoma, stomach carcinoma, liver cancer, and the top 5 CDK6 amplification-associated cancer types were lung adenocarcinoma, stomach carcinoma, liver cancer, melanoma, glioma. In addition, CDK4 amplification in Chinese cohort, 22 (11%) of the 203 Chinese bone and soft tissue sarcoma patients had CDK4 amplification, and 4 (2%) of the 203 had CDK6 amplification. Bone and soft tissue sarcoma types with CDK4 / 6 amplification including soft tissue sarcoma, bone cancer, fibrosarcoma, chondrosarcoma, rhabdomyosarcoma, liposarcoma, synovial sarcoma. Conclusions: Our study provided a characteristic of CDK4/6 amplification in Chinese and Western pan-cancer patients. Analysis revealed frequent CDK4 / 6 amplification in lung cancer, sarcoma, stomach carcinoma, ovarian carcinoma and liver cancer. It is suggested patient with these cancer types may potentially benefit from CDK4/6 inhibitor.

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.

CD24 Gene Polymorphism - A Novel Prognostic Factor in Esophageal Cancer

2014 ◽  
Vol 29 (1) ◽  
pp. e49-e54 ◽  
Author(s):  
Eran Sadot ◽  
Sarah Kraus ◽  
Michael Stein ◽  
Ilana Naboishchikov ◽  
Ohad Toledano ◽  
...  
Keyword(s):  
Esophageal Cancer ◽  
Cancer Patients ◽  
Poor Prognosis ◽  
Statistical Significance ◽  
Rflp Analysis ◽  
Tumor Stage ◽  
Control Group ◽  
Coding Region ◽  
Regional Lymph Nodes ◽  
Significant Difference

Background The CD24 gene has been correlated with poor prognosis of various malignancies. The significance of CD24 in esophageal cancer remains unknown. Our aim was to evaluate the association between CD24 genetic polymorphism and esophageal cancer. Materials and Methods Between June 2011 and May 2012 patients with esophageal cancer and healthy controls were prospectively enrolled and clinicopathological data were collected. Genomic DNA was extracted and restriction fragment length polymorphism (RFLP) analysis was performed to determine CD24 polymorphism at the coding region of CD24, which results in a substitution of the amino acid Ala by Val. Statistical significance was determined by unpaired t-test, χ2-test, and Fisher's exact test. Results A total of 102 patients were included, of whom 51 had esophageal cancer and the rest comprised a healthy control group. The incidence of the polymorphism variant (Val/Val) among the healthy subjects and the esophageal cancer cohort was 6% in both groups. The incidence of N3 (metastasis in 7 or more regional lymph nodes) was markedly higher in those esophageal cancer patients who carried the polymorphism variant compared with those who did not carry it (66% and 2%, respectively, p=0.007). No significant difference was found between the groups with regard to age, gender, histology type, tumor location, tumor stage, and other histological characteristics of the tumor. Conclusions This CD24 polymorphism may serve as a novel prognostic marker identifying esophageal cancer patients with poor prognosis. Further studies are warranted to evaluate CD24 function and to validate its predictive potential with regard to esophageal cancer.

scholarly journals Development and validation of a LRP1B mutation-associated prognostic model for hepatocellular carcinoma

2021 ◽  
Author(s):  
Jian Xu ◽  
Xiaomin Shen ◽  
Bo Zhang ◽  
Rui Su ◽  
Mingxuan Cui ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Gene Mutation ◽  
Prognostic Model ◽  
Immune Cell ◽  
Low Risk ◽  
Cell Infiltration ◽  
Immune Checkpoints ◽  
Immune Cell Infiltration ◽  
Significant Difference ◽  
Patient Prognosis

Abstract Purpose: To develop a LRP1B gene mutation based prognostic model for hepatocellular carcinoma (HCC) patients risk prediction. Methods: The LRP1B gene mutation rate was calculated from HCC patient samples. Meanwhile, differentially expressed genes according to LRP1B mutant were screened out for prognostic model establishment. Based on this innovative model, HCC patients were categoried into high and low-risk group. The immune status including immune cell infiltration ratio and checkpoints have been explored in two groups. Results: It can be shown here 11 genes demonstrate significant differences according to LRP1B status, which can better predict HCC patient prognosis. The accuracy of the model prediction is evaluated and approved by the AUC value. From the immune cell infiltration ratio analysis, there is a significant difference in the infiltration degree of 7 types of immune cells and 2 immune checkpoints between high and low-risk HCC patients. Meanwhile, LRP1B was tested as a prognostic marker in clinic to predict different stages for HCC with satisfied accurancy. Conclusion: This study has explored a potential prognostic biomarker and developed a novel LRP1B mutation-associated prognostic model for hepatocellular carcinoma, which provides a systematic reference for future better understanding of clinical research.

scholarly journals Bone metastasis of limb segments: Is mesometastasis another poor prognostic factor of cancer patients?

2020 ◽  
Vol 50 (6) ◽  
pp. 688-692
Author(s):  
Shoichiro Tani ◽  
Yutaka Morizaki ◽  
Kosuke Uehara ◽  
Ryoko Sawada ◽  
Hiroshi Kobayashi ◽  
...  
Keyword(s):  
Bone Metastasis ◽  
Prognostic Factor ◽  
Bone Metastases ◽  
Cancer Patients ◽  
Survival Curve ◽  
Lower Leg ◽  
Poor Prognostic Factor ◽  
Significant Difference ◽  
The University ◽  
Distal Site

Abstract Objective In contrast to acrometastasis, defined as bone metastasis to the hand or foot, the frequency and prognosis of bone metastasis of other limb segments remain unclear. To compare prognosis according to sites of bone metastasis, we defined two new terms in this study: ‘mesometastasis’ and ‘rhizometastasis’ as bone metastasis of ‘forearm or lower leg’ and ‘arm or thigh’, respectively. Methods A total of 539 patients who were registered to the bone metastasis database of The University of Tokyo Hospital from April 2012 to May 2016 were retrospectively surveyed. All patients who were diagnosed to have bone metastases in our hospital are registered to the database. Patients were categorized into four groups according to the most distal site of bone metastases: ‘acrometastasis’, ‘mesometastasis’, ‘rhizometastasis’ and ‘body trunk metastasis’. Results The frequency of rhizometastasis (22.5%) or body trunk metastasis (73.1%) was significantly higher than that of acrometastasis (2.0%) or mesometastasis (2.4%). The median survival time after diagnosis of bone metastases for each group was as follows: 6.5 months in acrometastasis, 4.0 months in mesometastasis, 16 months in rhizometastasis, 17 months in body trunk metastasis and 16 months overall. In survival curve, there was a statistically significant difference between mesometastasis and body trunk metastasis. Conclusions Our findings suggest that ‘mesometastasis’ could be another poor prognostic factor in cancer patients and that patients with mesometastasis should receive appropriate treatments according to their expected prognosis.

A DNA-mutational panel for liquid biopsy-based pan-cancer early detection.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e13687-e13687
Author(s):  
Zhao Yi ◽  
Weizhi Chen ◽  
Ji He
Keyword(s):  
Early Detection ◽  
Cancer Patients ◽  
Liquid Biopsy ◽  
Somatic Mutations ◽  
Asian Population ◽  
Plasma Samples ◽  
Sequencing Data ◽  
Cancer Early Detection ◽  
Chinese Cancer Patients ◽  
Pan Cancer

e13687 Background: Early detection through liquid biopsy can significantly increase the successful chances of treatment. The sensitivity and specificity of early detection are limited by lower signal-to-noise ratio. Thus, well design of liquid biopsy panel is important. Methods: We adopted comprehensive data sources for designing the liquid biopsy panel, including databases of TCGA, ICGC, COSMIC, MSK Cancer Hotspots, while the panel of HCCscreen and CancerSeek. We also considered the database of somatic mutations in Chinese cancer patients generated by us (Genecast (Beijing) Biotechnology Co., Ltd.). We first calculated pan-cancer carrier ratio of somatic mutations in each database and constructed the distribution of mutation counts on step-wise increased carrier ratio. Then, we selected the set of somatic mutations with “elbow point” carrier ratio from each database as part of the panel. Finally, we integrated collected hotspots with the panel of HCCscreen and CancerSeek. Results: We selected 408, 521, 214, 146 and 330 hotspots from databases of TCGA, ICGC, COSMIC, MSK Cancer Hotspots and somatic mutations in Chinese cancer patients, respectively. After integration with the panel of HCCscreen and CancerSeek, this designed panel contains 3,334 bases distributed on 23 chromosomes and 915 gene models. Comparison of hotspots collected from different databases showed that few of them shared the same genomic location except for ones from the database of MSK Cancer Hotspots, indicating the well complementarity between them. Especially, there are 186 unique hotspots collected from the database of somatic mutations in Chinese cancer patients, which can improve the sensitivity of early detection for Chinese and Asian population. Next, we evaluated detected sensitivity of the designed panel based on sequencing data of plasma samples from more than 12,000 Chinese cancer patients collected in Genecast. The result showed that the maximum sensitivity is 66.67% for small cell lung cancer and the overall sensitivity is 45.71% for 26 cancer types, in which hotspots uniquely collected from the database of somatic mutations in Chinese cancer patients accounted for 5.11%. Conclusions: We designed a liquid biopsy panel for pan-cancer early detection and evaluated its sensitivity based on sequencing data of plasma samples from more than 12,000 Chinese cancer patients. Satisfactory performance of our designed panel shows its potential application in cancer screening for healthy and highly risky individuals.

scholarly journals Development and validation of a LRP1B mutation-associated prognostic model for hepatocellular carcinoma

2021 ◽  
Author(s):  
Jian Xu ◽  
Xiaomin Shen ◽  
Bo Zhang ◽  
Rui Su ◽  
Mingxuan Cui ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Gene Mutation ◽  
Prognostic Model ◽  
Immune Cell ◽  
Low Risk ◽  
Cell Infiltration ◽  
Immune Checkpoints ◽  
Immune Cell Infiltration ◽  
Significant Difference

Purpose: To develop a LRP1B gene mutation based prognostic model for hepatocellular carcinoma (HCC) patients risk prediction. Methods: The LRP1B gene mutation rate was calculated from HCC patient samples. Meanwhile, differentially expressed genes according to LRP1B mutant were screened out for prognostic model establishment. Based on this innovative model, HCC patients were categoried into high and low-risk group. The immune status including immune cell infiltration ratio and checkpoints have been explored in two groups. The functions of LRP1B and risk factors in the model were verified using both in vivo and in vitro experiments. Results: It could be demonstrated that LRP1B was a potential negative predictor for HCC patients prognosis with high mutation frequency. The functions of LRP1B was verified with ELISA assay and Quantitative Real-time PCR method based on clinical recruited HCC participants. 11 genes displayed significant differences according to LRP1B status, which could better predict HCC patient prognosis. The functions of these genes were examined using HCC cell line HCCLM3, suggesting they played a pivotal role in determining HCC cell proliferation and apoptosis. From the immune cell infiltration ratio analysis, there was a significant difference in the infiltration degree of 7 types of immune cells and 2 immune checkpoints between high and low-risk HCC patients. Conclusion: This study hypothesized a potential prognostic biomarker and developed a novel LRP1B mutation-associated prognostic model for hepatocellular carcinoma, which provided a systematic reference for future understanding of clinical research.

scholarly journals Combination of Endogenous Estradiol and Adipokine Leptin in Breast Cancer Risk and Prognosis Assessment in Postmenopausal Chinese Women

2021 ◽  
Vol 12 ◽  
Author(s):  
Yang Luo ◽  
Han-Bing Li ◽  
Yue Zhang ◽  
Yu-Xin Wu ◽  
Di Shen ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Breast Cancer Risk ◽  
Cancer Risk ◽  
Cancer Patients ◽  
Healthy Subjects ◽  
Chinese Women ◽  
Postmenopausal Breast Cancer ◽  
Breast Cancer Patients ◽  
Poor Prognostic Factor ◽  
Significant Difference

ObjectiveOur study aims to clarify the role of estradiol and leptin in breast cancer risk and prognostic assessment in postmenopausal Chinese women.DesignThe serum circulating estradiol and leptin level was detected by ELISA. Then the correlation between estradiol, leptin level, and clinical characteristics was analyzed using Fisher’s exact test. Next, the Kaplan-Meier model was used to analyze the association between estradiol, leptin, and prognosis of postmenopausal breast cancer patients in our cohort and the TCGA dataset.SettingThe study was conducted at the National Cancer Center, Cancer Hospital, Chinese Academy of Medical Sciences, and Peking Union Medical College.PatientsA total of 182 postmenopausal breast cancer patients and 111 healthy subjects from January 2010 to August 2010 were included in the analysis. Another 702 cases with breast cancer were retrieved from The Cancer Genome Atlas (TCGA) database for subsequent analysis.Main Outcome MeasureSerum circulating estradiol and leptin level.ResultsThe level of estradiol was significantly higher (P&lt;0.001) but the level of leptin had no significant difference (P = 0.764) in postmenopausal breast cancer patients compared with healthy subjects. The level of estradiol and leptin was not significantly different between estrogen receptor (ER) positive and ER-negative groups (P&gt;0.05). Estradiol was significantly correlated with tumor T stage (P = 0.002) and leptin was significantly associated with perineural invasion (P = 0.014). In addition, the disease-free survival of patients with a high level of estradiol was significantly shorter (P = 0.025) but leptin tended to be a protective factor for overall survival in TCGA analysis (P = 0.038).ConclusionCirculating estradiol and leptin played important roles in the risk of postmenopausal breast cancer even in low-estrogen nations with an independent expression of ER status. High circulating estradiol was a poor prognostic factor and leptin may be a protection signal in Chinese postmenopausal patients with breast cancer.

Relationship of liver cancer with LRP1B or TP53 mutation and tumor mutation burden and survival.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 1573-1573 ◽  
Author(s):  
Longrong Wang ◽  
Kai Yan ◽  
Jiamin Zhou ◽  
Ning Zhang ◽  
Miao Wang ◽  
...  
Keyword(s):  
Liver Cancer ◽  
Tp53 Mutation ◽  
Liver Tumors ◽  
Checkpoint Inhibitors ◽  
Poor Prognostic Factor ◽  
Tumor Mutation Burden ◽  
Synonymous Mutations ◽  
Clinical Cohort ◽  
Mutation Burden ◽  
Significant Difference

1573 Background: Liver cancer (LC), one of the most common causes of cancer-related deaths, is a serious medical problem due to the limited treatment options available for this disease. Immune checkpoint inhibitors (ICIs) that are proved to be beneficial in the treatment of advanced LC. Similar to observations in other cancers, these ICIs as monotherapy may benefit only a fraction of HCC patients. Tumor mutation burden (TMB) is an important predictor for efficacy of ICIs in several solid tumors. However, the research on exploring the association between TMB and mutant genes with high frequency of liver cancer is limited. Besides, previous research on prognostic factors primarily focus on pathological features, probing the effects of genetic variations are urgently needed to study. Methods: Whole-exome sequencing data of 377 liver tumors from the Cancer Genome Altas (TCGA) and next generation sequencing (NGS) data of 655 liver tumors from Chinese clinical dataset were analyzed to explore the associated between LRP1B or TP53 gene alteration and TMB. TMB was defined as total number of somatic non-synonymous mutations in coding region. Results: In total, 9.3% (35/377) of hepatic tumors in TCGA and 7.8% (51/655) in clinical cohort harboring LRP1B mutation. LRP1B mutation was significantly associated with higher TMB in both TCGA cohort (P = 0.0003) and clinical cohort (P = 0.0005). The frequency of TP53 mutation was 28.1% (106/377) in TCGA cohort, however, TP53 mutation represented a greater rate of 54.5% (357/655) in Chinese clinical cohort. TP53 mutation was also associated with higher TMB in the two cohort (P = 0.0005 for the TCGA cohort and P = 0.0010 for the clinical cohort). In addition, prognosis analysis was performed on patients in TCGA cohort. LRP1B statue resulted in significantly shorter overall survival (OS, median, 20.9 vs 61.7 months; HR, 2.22; P = 0.0012), and a decreasing trend on progression-free survival (PFS) without significant difference (median, 8.7 vs 16.6 months; HR, 1.28; P = 0.2839). TP53 mutation was an independent risk factors affecting both OS (HR 1.58, P = 0.0109) and PFS (HR 1.59, P = 0.0027), respectively. Conclusions: The results indicated that LRP1B or TP53 mutation was a poor prognostic factor in LC, and patients harboring any of these two gene mutations might easily benefit from the immunotherapy.

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