scholarly journals Machine learning of genomic features in organotropic metastases stratifies progression risk of primary tumors

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Biaobin Jiang ◽  
Quanhua Mu ◽  
Fufang Qiu ◽  
Xuefeng Li ◽  
Weiqi Xu ◽  
...  
Keyword(s):  
Early Stage ◽  
Metastatic Cancer ◽  
Disease Free Survival ◽  
Risk Groups ◽  
Sequencing Data ◽  
Primary Tumors ◽  
Genomic Features ◽  
Stratification Method ◽  
Organ Specific ◽  
Spatiotemporal Behavior

AbstractMetastatic cancer is associated with poor patient prognosis but its spatiotemporal behavior remains unpredictable at early stage. Here we develop MetaNet, a computational framework that integrates clinical and sequencing data from 32,176 primary and metastatic cancer cases, to assess metastatic risks of primary tumors. MetaNet achieves high accuracy in distinguishing the metastasis from the primary in breast and prostate cancers. From the prediction, we identify Metastasis-Featuring Primary (MFP) tumors, a subset of primary tumors with genomic features enriched in metastasis and demonstrate their higher metastatic risk and shorter disease-free survival. In addition, we identify genomic alterations associated with organ-specific metastases and employ them to stratify patients into various risk groups with propensities toward different metastatic organs. This organotropic stratification method achieves better prognostic value than the standard histological grading system in prostate cancer, especially in the identification of Bone-MFP and Liver-MFP subtypes, with potential in informing organ-specific examinations in follow-ups.

scholarly journals Machine learning of genomic features in organotropic metastases stratifies progression risk of primary tumors

2020 ◽  
Author(s):  
Jiguang Wang ◽  
Biaobin Jiang ◽  
Quanhua Mu ◽  
Fufang Qiu ◽  
Weiqi Xu
Keyword(s):  
Early Stage ◽  
Metastatic Cancer ◽  
Risk Groups ◽  
Sequencing Data ◽  
Computational Framework ◽  
Primary Tumors ◽  
Genomic Features ◽  
Organ Specific ◽  
Spatiotemporal Behavior ◽  
Prostate Cancers

Abstract Metastasis leads to most cancer deaths, but its spatiotemporal behavior remains unpredictable at early stage. Here, we developed MetaNet, a computational framework that integrates clinical and sequencing data from 32,176 primary and metastatic cancer cases, to assess metastatic risks of primary tumors. MetaNet achieved high accuracy in distinguishing the metastasis from the primary in breast and prostate cancers. From the prediction, we identified Metastasis-Featuring Primary (MFP) tumors, a subset of primary tumors with genomic features enriched in metastasis, and demonstrated their high metastatic risks with significantly shorter disease-free survivals and higher migratory potential. In addition, we identified genomic alterations associated with organ-specific metastases, and employed them to stratify patients into the risk groups with propensities toward different metastatic organs. Remarkably, this organotropic stratification achieved better prognostic value than standard histological grading system in prostate cancer, especially between Bone-MFP and Liver-MFP subtypes, with organotropic insights to inform organ-specific examinations in follow-ups.

Clinical characteristics, genomic features, and recurrence risk of early-stage MET exon 14 mutant non-small cell lung cancer (NSCLC).

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 9042-9042
Author(s):  
Gonzalo Recondo ◽  
Robin Guo ◽  
Paola Cravero ◽  
Biagio Ricciuti ◽  
Christina Falcon ◽  
...  
Keyword(s):  
Molecular Subtype ◽  
Early Stage ◽  
Smoking Status ◽  
Disease Free Survival ◽  
Stage I ◽  
Cancer Center ◽  
Early Stage Disease ◽  
Genomic Features ◽  
Metastatic Setting ◽  
Resected Stage

9042 Background: MET exon 14 alterations occur in ~3% of patients (pts) with NSCLC. Although clinical and genomic features of MET exon 14 mutant (mut) NSCLC are better characterized in the metastatic setting, less is known about early-stage disease for this molecular subtype. Methods: Clinicopathologic and genomic data were collected from patients (pts) with resected stage I-III MET exon 14 mutant NSCLC at the Dana-Farber Cancer Institute (DFCI) and the Memorial Sloan Kettering Cancer Center (MSKCC). We estimated the disease-free survival (DFS) and overall survival (OS) of patients from the date of surgical resection. The prevalence of MET exon 14 mutations in stage I-III NSCLC was assessed using OncoPanel NGS v3.0 at DFCI. Results: The prevalence of MET exon 14 alterations in resected tumors of pts with stage I-III NSCLC at DFCI using Oncopanel v3 was 2.8% (17/613) overall: 2.9% (16/542) in non-squamous and 1.4% (1/71) in squamous histology. We identified 131 pts with resected stage I-III (I = 73, II = 28, III = 30) MET exon 14 mut NSCLC at DFCI (Oncopanel v1-v3) and MSKCC (MSK-IMPACT), with a median age of 71 years (yrs) (range: 43-88). There were no significant differences in sex, smoking status, or type of MET alteration across stages. In stage I resected tumors there was a higher proportion of adenocarcinoma histology compared to stages II and III (p = 0.009). The median harmonized TMB (mTMB) was similar across stages (p = 0.43). Common genomic co-alterations included MET amplification (amp) (5.3%), CDK4/ 6 amp (19.1%), MDM2 amp (35.1%), TP53 mut (17.6%) and CDKN2A/ B loss (9.2%). The median DFS in stage I, II, and III NSCLC was 8.3 yrs (95% CI: 3.1-8.3), 2.6 yrs (95% CI: 1.0-2.6), and 2.1 yrs (95% CI: 0.7-2.7), respectively (p = 0.017). The median OS in stage I, II, and III NSCLC was 9.2 yrs (95% CI: 8.5 -10.5), not reached (NR) (95% CI: NR-NR), and 4.1 yrs (95% CI: 3.6-4.1), respectively (p = 0.052). Concurrent MET amp was independently associated with worse DFS (HR: 4.9, 95% CI: 1.8-13.1; p = 0.002) in multivariate analysis. Conclusions: MET exon 14 mutations are present in 2.8% of resected stage I-III NSCLCs. Given the prevalence of this molecular alteration in early-stage NSCLC, clinical trials exploring the role of adjuvant and neoadjuvant MET targeted therapies in this population may be warranted.

scholarly journals Lymph Node Involvement in Early-Stage Cervical Cancer: Is Lymphangiogenesis a Risk Factor? Results from the MICROCOL Study

Cancers ◽  
2022 ◽  
Vol 14 (1) ◽  
pp. 212
Author(s):  
Matteo Tantari ◽  
Stefano Bogliolo ◽  
Matteo Morotti ◽  
Vincent Balaya ◽  
Florent Bouttitie ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Risk Factor ◽  
Lymph Node ◽  
Early Stage ◽  
Lymphatic Vessels ◽  
Disease Free Survival ◽  
Lymph Node Involvement ◽  
Pelvic Lymph Node ◽  
Primary Tumors ◽  
Early Stage Cervical Cancer

Background: In patients with cervical cancer, the presence of tumoral lymph-vascular space invasion (LVSI) is the main risk factor for pelvic lymph node metastasis (PLNM). The objective of this study was to evaluate the presence of several markers of lymphangiogenesis in early-stage cervical cancer and their correlation with PLNM and tumoral recurrence. Materials and Methods: Seventy-five patients with early-stage cervical carcinoma underwent sentinel lymph node (SLN) sampling in association with complete pelvic lymph node dissection. Primary tumors were stained with the following markers: Ki67, D2-40, CD31 and VEGF-C. A 3-year follow-up was performed to evaluate the disease-free survival. Results: Overall, 14 patients (18.6%) had PLNM. Positive LVSI was seen in 29 patients (38.6%). There was a significant correlation between LVSI evidenced by H/E staining and PLNM (p < 0.001). There was no correlation between high Ki67, CD31, D2-40, and VEGF-C staining with PLNM or tumor recurrence. Conclusions: Our data support that lymphatic spread does not require the proliferation of new lymphatic endothelial cells in early-stage cervical cancer. These results emphasize the importance of pre-existing peritumoral lymphatic vessels in the metastatic process in early cervical cancer. None of the markers of lymphangiogenesis and proliferation assessed in this study were predictive of PLNM or recurrence.

scholarly journals Comparison of Mismatch Repair Status Between Primary and Matched Metastatic Sites in Patients With Colorectal Cancer

2019 ◽  
Vol 17 (10) ◽  
pp. 1174-1183 ◽  
Author(s):  
Wen-Zhuo He ◽  
Wan-Ming Hu ◽  
Fang Wang ◽  
Yu-Ming Rong ◽  
Lin Yang ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Lymph Node ◽  
Metastatic Cancer ◽  
Ovarian Metastasis ◽  
Primary Cancer ◽  
Metastatic Tumors ◽  
Primary Tumors ◽  
Organ Specific ◽  
High Concordance ◽  
Node Metastases

Background: Differences between the features of primary cancer and matched metastatic cancer have recently drawn attention in research. This study investigated the concordance in microsatellite instability (MSI) and mismatch repair (MMR) status between primary and corresponding metastatic colorectal cancer (CRC). Methods: Consecutive patients with metastatic CRC who had both primary and metastatic tumors diagnosed at our institution in January 2008 through December 2016 were identified. Immunohistochemistry was used to test the MMR status of both primary and matched metastatic tumors, and PCR analysis was performed to test MSI in patients with deficient MMR (dMMR) status. Results: A total of 369 patients were included. Of the 46 patients with MSI-high primary tumors, 37 (80.4%) also had MSI-high metastatic tumors, whereas 9 (19.6%) had microsatellite stable (MSS) metastatic tumors. A high concordance was found in patients with liver, lung, or distant lymph node metastases. Interestingly, the discrepancy was more likely to be limited to peritoneal (5/20) or ovarian (4/4) metastasis (chi-square test, P<.001). These organ-specific features were also found in the pooled analysis. Along with the change of MSI-high in primary cancer to MSS in metastatic cancer, lymphocyte infiltration decreased significantly (P=.008). However, the change did not influence survival; the median overall survival of MSI-high and MSS metastatic tumors was 21.3 and 21.6 months, respectively (P=.774). The discrepancy rate was 1.6% for patients with proficient MMR primary tumors. Conclusions: For patients with dMMR primary tumors, the concordance of MSI and MMR status in primary CRC and corresponding metastatic cancer is potentially organ-specific. High concordance is found in liver, lung, and distant lymph node metastases, whereas discrepancy is more likely to occur in peritoneal or ovarian metastasis. Rebiopsy to evaluate MSI-high/dMMR status might be needed during the course of anti–PD-1 therapy in cases of peritoneal or ovarian metastasis.

scholarly journals Clinical implications of low skeletal muscle mass in early-stage breast and colorectal cancer

2018 ◽  
Vol 77 (4) ◽  
pp. 382-387 ◽  
Author(s):  
Elizabeth Cespedes Feliciano ◽  
Wendy Y. Chen
Keyword(s):  
Colorectal Cancer ◽  
Skeletal Muscle ◽  
Body Composition ◽  
Muscle Mass ◽  
Skeletal Muscle Mass ◽  
Early Stage ◽  
Metastatic Cancer ◽  
Disease Free Survival ◽  
Metastatic Breast ◽  
Metastatic Setting

Although obesity has now been widely accepted to be an important risk factor for cancer survival, the associations between BMI and cancer mortality have not been consistently linear. Although morbid obesity has clearly been associated with worse survival, some studies have suggested a U-shaped association with no adverse association with overweight or lower levels of obesity. This ‘obesity paradox’ may be due to the fact that BMI likely incompletely captures key measures of body composition, including distribution of skeletal muscle and adipose tissue. Fat and lean body mass can be measured using clinically acquired computed tomography scans. Many of the earlier studies focused on patients with metastatic cancer. However, skeletal muscle loss in the metastatic setting may reflect end-stage disease processes. Therefore, this article focuses on the clinical implication of low skeletal muscle mass in early-stage non-metastatic breast and colorectal cancer where measures of body composition have been shown to be strong predictors of disease-free survival and overall survival and also chemotherapy toxicity and operative risk.

scholarly journals An Autophagy-Related Gene Signature Predicts Prognosis of Early Stage Colorectal Cancer

2020 ◽  
Author(s):  
Yi-feng Zou ◽  
Qiu-ning Wu ◽  
Si Qin ◽  
Xi Xi Chen ◽  
Jia-wei Cai ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Validation Cohort ◽  
Early Stage ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Disease Free Survival ◽  
Risk Groups ◽  
Related Gene ◽  
Training Cohort ◽  
Inflammatory Processes

Abstract Background and aimsA certain number of early-stage colorectal cancer (CRC) patients suffer tumor recurrence after initial curative resection. In this context, an effective prognostic biomarker model is constantly in need. Autophagy exhibits a dual role in tumorigenesis. Our study aims to develop an autophagy-related gene (ATG) signature based on high-throughput data analysis for disease-free survival (DFS) prognosis of patients with stage I/II CRC.MethodsGene expression profiles and clinical information of CRC patients extracted from four public datasets were divided into training cohort (GSE39582, n=566), validation cohort (TCGA CRC, n=624), and meta-validation cohort (GSE37892 and GSE14333, n=420). Autophagy genes significantly associated with prognosis were identified.ResultsAmong 655 autophagy-related genes, a 10 gene ATG signature, which was significantly associated with DFS in the training cohort (HR, 2.76[1.56–4.82]; P=2.06×10-4), was constructed. The ATG signature, stratifying patients into high and low autophagy risk groups, was validated in the validation (HR, 2.29[1.15–4.55]; P=1.5×10-2) and the meta-validation cohorts (HR, 2.5[1.03–6.06]; P=3.63×10-2), and proved to be prognostic in a multivariate analysis. Functional analysis revealed enrichment of several immune/ inflammatory processes in the high autophagy risk group, where significantly higher infiltration of T regulatory cells (Tregs) was observed.ConclusionsOur study established a prognostic ATG signature that effectively predicted DFS for early-stage CRC patients. Meanwhile, the study also revealed the possible correlation between autophagy and immune/ inflammatory processes and tumorigenesis.

scholarly journals Myeloperoxidase Genotypes and Enhanced Efficacy of Chemotherapy for Early-Stage Breast Cancer in SWOG-8897

2009 ◽  
Vol 27 (30) ◽  
pp. 4973-4979 ◽  
Author(s):  
Christine B. Ambrosone ◽  
William E. Barlow ◽  
Wanda Reynolds ◽  
Robert B. Livingston ◽  
I-Tien Yeh ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Risk Group ◽  
Early Stage ◽  
Disease Free Survival ◽  
Risk Groups ◽  
High Risk Group ◽  
Independent Study ◽  
Prognostic Features ◽  
Fold Reduction ◽  
Cox Proportional Hazard Models

Purpose Myeloperoxidase (MPO) generates reactive oxygen species and also activates xenobiotics . In a rigorous clinical trial (Southwest Oncology Group SWOG-8897), we examined relationships between genotypes and disease-free survival (DFS) among women treated for breast cancer, as well as those who did not receive adjuvant chemotherapy. Patients and Methods Patients were assigned to risk groups according to standard prognostic features; the low-risk group (n = 753 genotyped) received follow-up only, and the high-risk group (n = 401 genotyped) was randomly assigned to adjuvant cyclophosphamide, methotrexate, and fluorouracil (CMF) or cyclophosphamide, doxorubicin, and fluorouracil (CAF), with or without tamoxifen. DNA from archived normal lymph node tissue was genotyped, and Cox proportional hazard models were used to calculate DFS associated with MPO genotypes. Results Among women in the treatment arm, those with MPO G alleles had more than a two-fold reduction in hazard of recurrence (adjusted hazard ratio [HR] for GA genotypes, 0.51; 95% CI, 0.21 to 0.99; HR for GG genotypes, 0.41; 95% CI, 0.21 to 0.77). Effects were greatest among women who were further randomly assigned to tamoxifen (HR for GA genotypes, 0.28; 95% CI, 0.12 to 0.69; HR for GG genotypes, 0.19; 95% CI, 0.08 to 0.45). There were no significant associations between genotypes and DFS among women in the untreated arm, and relationships between genotypes and DFS did not differ by CAF or CMF. Conclusion These results, observed in two independent study populations, indicate that high-activity MPO genotypes are associated with better survival among women receiving cyclophosphamide-containing therapy, particularly when followed by tamoxifen therapy. MPO can be inhibited and/or upregulated by commonly used drugs; thus, our findings merit further investigation for optimization of therapeutics for breast cancer.

scholarly journals Identification of an Autophagy-Related Gene Signature for the Prediction of Prognosis in Early-Stage Colorectal Cancer

2021 ◽  
Vol 12 ◽  
Author(s):  
Xu-tao Lin ◽  
Qiu-ning Wu ◽  
Si Qin ◽  
De-jun Fan ◽  
Min-yi Lv ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Validation Cohort ◽  
Early Stage ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Disease Free Survival ◽  
Clinical Information ◽  
Risk Groups ◽  
Related Gene ◽  
Training Cohort

Purpose: A certain number of early-stage colorectal cancer (CRC) patients suffer tumor recurrence after initial curative resection. In this context, an effective prognostic biomarker model is constantly in need. Autophagy exhibits a dual role in tumorigenesis. Our study aims to develop an autophagy-related gene (ATG) signature-based on high-throughput data analysis for disease-free survival (DFS) prognosis of patients with stage I/II CRC.Methods: Gene expression profiles and clinical information of CRC patients extracted from four public datasets were distributed to discovery and training cohort (GSE39582), validation cohort (TCGA CRC, n = 624), and meta-validation cohort (GSE37892 and GSE14333, n = 420). Autophagy genes significantly associated with prognosis were identified.Results: Among 655 autophagy-related genes, a 10-gene ATG signature, which was significantly associated with DFS in the training cohort (HR, 2.76[1.56–4.82]; p = 2.06 × 10–4), was constructed. The ATG signature, stratifying patients into high and low autophagy risk groups, was validated in the validation (HR, 2.29[1.15–4.55]; p = 1.5 × 10–2) and meta-validation cohorts (HR, 2.5[1.03–6.06]; p = 3.63 × 10–2) and proved to be prognostic in a multivariate analysis. Functional analysis revealed enrichment of several immune/inflammatory pathways in the high autophagy risk group, where increased infiltration of T regulatory cells (Tregs) and decreased infiltration of M1 macrophages were observed.Conclusion: Our study established a prognostic ATG signature that effectively predicted DFS for early-stage CRC patients. Meanwhile, the study also revealed the possible relationship among autophagy process, immune/inflammatory response, and tumorigenesis.

scholarly journals An Autophagy-Related Gene Signature Predicts Prognosis of Early Stage Colorectal Cancer

2020 ◽  
Author(s):  
Yi-feng Zou ◽  
Qiu-ning Wu ◽  
Si Qin ◽  
Xi Xi Chen ◽  
Jia-wei Cai ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Validation Cohort ◽  
Early Stage ◽  
Expression Profiles ◽  
Disease Free Survival ◽  
Clinical Information ◽  
Risk Groups ◽  
Related Gene ◽  
Training Cohort ◽  
Inflammatory Processes

Abstract Background and aimsA certain number of early-stage colorectal cancer (CRC) patients suffer tumor recurrence after initial curative resection. In this context, an effective prognostic biomarker model is constantly in need. Autophagy exhibits a dual role in tumorigenesis. Our study aims to develop an autophagy-related gene (ATG) signature based on high-throughput data analysis for disease-free survival (DFS) prognosis of patients with stage I/II CRC.MethodsGene expression profiles and clinical information of CRC patients extracted from four public datasets were divided into training cohort (GSE39582, n=566), validation cohort (TCGA CRC, n=624), and meta-validation cohort (GSE37892 and GSE14333, n=420). Autophagy genes significantly associated with prognosis were identified.ResultsAmong 655 autophagy-related genes, a 10 gene ATG signature, which was significantly associated with DFS in the training cohort (HR, 2.76[1.56–4.82]; P=2.06×10-4), was constructed. The ATG signature, stratifying patients into high and low autophagy risk groups, was validated in the validation (HR, 2.29[1.15–4.55]; P=1.5×10-2) and the meta-validation cohorts (HR, 2.5[1.03–6.06]; P=3.63×10-2), and proved to be prognostic in a multivariate analysis. Functional analysis revealed enrichment of several immune/ inflammatory processes in the high autophagy risk group, where significantly higher infiltration of T regulatory cells (Tregs) was observed.ConclusionsOur study established a prognostic ATG signature that effectively predicted DFS for early-stage CRC patients. Meanwhile, the study also revealed the possible correlation between autophagy and immune/ inflammatory processes and tumorigenesis.

Sign in / Sign up

Export Citation Format

Share Document