scholarly journals Developmental Deconvolution for Classification of Cancer Origin

2021 ◽  
Author(s):  
Enrico Moiso ◽  
Alexander Farahani ◽  
Hetal Marble ◽  
Austin Hendricks ◽  
Samuel Mildrum ◽  
...  
Keyword(s):  
Developmental Trajectories ◽  
Unknown Primary ◽  
Tumor Type ◽  
Developmental Origins ◽  
Developmental Programs ◽  
Patients With Cancer ◽  
Type D ◽  
Cancer Types ◽  
Mlp Classifier

Cancer is a disease manifesting in abrogation of developmental programs, and malignancies are named based on their cell or tissue of origin. However, a systematic atlas of tumor origins is lacking. Here we map the single cell organogenesis of 56 developmental trajectories to the transcriptomes of over 10,000 tumors across 33 cancer types. We use this map to deconvolute individual tumors into their constituent developmental trajectories. Based on these deconvoluted developmental programs, we construct a Developmental Multilayer Perceptron (D-MLP) classifier that outputs cancer origin. The D-MLP classifier (ROC-AUC: 0.974 for top prediction) outperforms classification based on expression of either oncogenes or highly variable genes. We analyze tumors from patients with cancer of unknown primary (CUP), selecting the most difficult cases where extensive multimodal workup yielded no definitive tumor type. D-MLP revealed insights into developmental origins and diagnosis for most patient tumors. Our results provide a map of tumor developmental origins, provide a tool for diagnostic pathology, and suggest developmental classification may be a useful approach for otherwise unclassified patient tumors.

scholarly journals Management of cancer of unknown primary

2020 ◽  
Vol 48 (2-3) ◽  
pp. 85-88
Author(s):  
Iva Andrašek ◽  
◽  
Mirna Ravlić ◽  
Martina Mikulandra ◽  
Franjo Cmrečak ◽  
...  
Keyword(s):  
Metastatic Tumor ◽  
Cancer Of Unknown Primary ◽  
Primary Site ◽  
Unknown Primary ◽  
Combined Modality Treatment ◽  
Tumor Type ◽  
Patients With Cancer ◽  
Poorly Differentiated ◽  
Primary Origin ◽  
Chemotherapy Agents

Cancer of an unknown primary site is most commonly an aggressive metastatic tumor with a median patient survival of 6 to 9 months. Histologically, it is predominantly adenocarcinoma, and if the primary site is subsequently diagnosed, it is usually the pancreas or lung. Biopsy should be performed whenever possible to classify a tumor of unknown primary origin into one of the following entities: adenocarcinoma, poorly differentiated carcinoma with characteristics similar to adenocarcinoma, squamous cell carcinoma, neuroendocrine carcinoma, poorly differentiated neoplasm. After determining the primary tumor type, the subtype is determined by immunohistochemical staining. In oligometastatic disease, there is a possibility of surgical treatment. Radiotherapy is used as a part of combined modality treatment. Most patients with cancer of unknown primary have an unfavorable prognosis despite multiple chemotherapy agents, and no protocol can be recommended as standard therapy.

scholarly journals The Value of PD-L1 Expression in Predicting the Efficacy of Anti-PD-1 or Anti-PD-L1 Therapy in Patients with Cancer: A Systematic Review and Meta-Analysis

2020 ◽  
Vol 2020 ◽  
pp. 1-14
Author(s):  
Xiao-Jiang Chen ◽  
Shu-Qiang Yuan ◽  
Jin-Ling Duan ◽  
Yong-Ming Chen ◽  
Shi Chen ◽  
...  
Keyword(s):  
Overall Survival ◽  
Hazard Ratio ◽  
Cochrane Library ◽  
Tumor Type ◽  
Combination Therapies ◽  
Advanced Cancer Patients ◽  
Scoring Method ◽  
Patients With Cancer ◽  
Risk Of Death ◽  
Cancer Types

Objectives. Recent trials have shown an overall survival (OS) benefit in 10-40% advanced cancer patients treated with programmed cell death 1 (PD-1) or programmed death-ligand 1 (PD-L1) inhibitors. Here, we aimed to evaluate the relationship between PD-L1 expression and the therapeutic efficacy of PD-1 or PD-L1 inhibitors in patients with cancer with recurrent or metastatic disease, compared with control treatments. Methods. We systematically searched Medline (PubMed), Embase, and Cochrane Library databases up to Jan 2019 and pooled the treatment effects (hazard ratio or relative ratio) of PD-1/PD-L1 inhibitors in patients with different PD-L1 expression. Results. Overall, twenty-four qualifying trials with over 14,860 subjects were eligible in this study. Compared with conventional agents, anti-PD/PD-L1 drugs significantly reduced the risk of death (hazard ratio 0.72, 95% CI 0.66 to 0.78), irrespective of the tumor type. Additionally, when PD-L1 expression ≥1% was defined as positive, anti-PD-1/PD-L1 monotherapy correlated with prolonged overall survival in patients with nonsmall cell lung cancer (NSCLC) (0.72, 0.61 to 0.86) and other cancer types (0.66, 0.57 to 0.76) patients with PD-L1 positive, rather than those with PD-L1 negative (hazard ratio for NSCLC and other cancer types: 0.84 and 0.87, respectively; all P > 0.05 ). The subgroup analyses to experimental agents, PD-1/PD-L1 inhibitors, PD-L1 antibody clone, and type of IHC scoring method validated the robustness of these findings. However, anti-PD-1/PD-L1 combination therapies can reduce the risk of death for patients with different cancer types, regardless of PD-L1 expression ( P < 0.05 for all PD-L1 expression status). Conclusions. We recommend PD-L1 expression as a predictive biomarker in patient selection for anti-PD-1/PD-L1 monotherapy, but not for combination therapies.

scholarly journals Hierarchical Classification of Cancers of Unknown Primary Using Multi-Omics Data

2019 ◽  
Vol 18 ◽  
pp. 117693511987216 ◽  
Author(s):  
Elham Bavafaye Haghighi ◽  
Michael Knudsen ◽  
Britt Elmedal Laursen ◽  
Søren Besenbacher
Keyword(s):  
Metastatic Cancer ◽  
Hierarchical Classification ◽  
Molecular Data ◽  
Unknown Primary ◽  
Cancer Type ◽  
Omics Data ◽  
Data Types ◽  
Cancer Types ◽  
Hierarchical Classifier

A cancer of unknown primary (CUP) is a metastatic cancer for which standard diagnostic tests fail to locate the primary cancer. As standard treatments are based on the cancer type, such cases are hard to treat and have very poor prognosis. Using molecular data from the metastatic cancer to predict the primary site can make treatment choice easier and enable targeted therapy. In this article, we first examine the ability to predict cancer type using different types of omics data. Methylation data lead to slightly better prediction than gene expression and both these are superior to classification using somatic mutations. After using 3 data types independently, we notice some differences between the classes that tend to be misclassified, suggesting that integrating the data might improve accuracy. In light of the different levels of information provided by different omics types and to be able to handle missing data, we perform multi-omics classification by hierarchically combining the classifiers. The proposed hierarchical method first classifies based on the most informative type of omics data and then uses the other types of omics data to classify samples that did not get a high confidence classification in the first step. The resulting hierarchical classifier has higher accuracy than any of the single omics classifiers and thus proves that the combination of different data types is beneficial. Our results show that using multi-omics data can improve the classification of cancer types. We confirm this by testing our method on metastatic cancers from the MET500 dataset.

STEROIDSTOFFWECHSEL BEI BRUSTKREBS. III.

1959 ◽  
Vol XXXII (I) ◽  
pp. 23-32 ◽  
Author(s):  
Kurt Schubert ◽  
Hans Schröder
Keyword(s):  
Advanced Cancer ◽  
Liver Damage ◽  
Adsorption Chromatography ◽  
Hepatic Insufficiency ◽  
Loading Test ◽  
Patients With Cancer ◽  
Urinary Steroids ◽  
Normal Women

ABSTRACT A testosterone test using two different dosages was carried out simultaneously in 7 women suffering from metastasizing carcinoma of the mamma and in 3 normal women. In each case the urinary steroids were estimated before the beginning of the test and after administration of 50 mg and 100 mg of testosterone respectively; the interval between the single estimations being one week. The use of fractionated hydrolysis enabled a mild fission of the conjugates and the classification of the products into free steroids, glucuronosides, sulfates and unknown conjugates. The 17-ketosteroids and the testosterone were estimated by means of Girard's separation and adsorption chromatography. During the loading test with testosterone different behaviours became evident, which had not been realized before. The behaviour of the 17-ketosteroids rendered possible the differentiation of normal women from patients with cancer of the breast yet without hepatic insufficiency, and furthermore of these latter ones from those with a liver damage in addition to the cancer of the breast. The glucuronosides of the 17-ketosteroids are only depressed, when there exists a pronounced damage of the liver; the loading test making possible an extension of the range of recognizable damages. Furthermore, the behaviour of dehydroepiandrosterone (II/III), of androsterone (IV), and of aetiocholanolone (V) lends itself to this differentiation. In advanced cancer of the breast the values of II/III are invariably low, whilst IV and V often increase temporarily. The relation of IV to V may be altered in a different way. The excretion of not transformed testosterone is less in patients than in normal women and especially low in patients with liver damage.

scholarly journals Pan-cancer analysis of CD274 (PD-L1) mutations in 314,631 patient samples and subset correlation with PD-L1 protein expression

2021 ◽  
Vol 9 (6) ◽  
pp. e002558
Author(s):  
Richard S.P. Huang ◽  
Brennan Decker ◽  
Karthikeyan Murugesan ◽  
Matthew Hiemenz ◽  
Douglas A. Mata ◽  
...  
Keyword(s):  
Protein Expression ◽  
Checkpoint Inhibitors ◽  
Endometrial Adenocarcinoma ◽  
Primary Melanoma ◽  
B Cell Lymphoma ◽  
Unknown Primary ◽  
Future Research ◽  
Tumor Type ◽  
Missense Mutations ◽  
L1 Protein

BackgroundThe effects of non-amplification short variant (SV) mutations in CD274 (programmed death-ligand 1 (PD-L1)) on PD-L1 protein expression and immune checkpoint inhibitors (ICPIs) therapy are unknown. Here, we present a retrospective analysis of CD274 mutations detected by comprehensive genomic profiling (CGP) and correlate these results with tumor-cell PD-L1 immunohistochemistry (IHC)-based expression assessment to better understand the relationship between mutations and protein expression of PD-L1.MethodsCGP was performed on hybridization-captured, adaptor ligation-based libraries using DNA and/or RNA extracted from 314,631 tumor samples that were sequenced for up to 406 cancer-related genes and select gene rearrangements. PD-L1 IHC was performed on a subset of cases (n=58,341) using the DAKO 22C3 PD-L1 IHC assay and scored with the tumor proportion score (TPS).ResultsOverall, the prevalence of CD274 SV mutations was low (0.3%, 1081/314,631) with 577 unique variants. The most common CD274 SV mutations were R260H (n=51), R260C (n=18), R125Q (n=12), C272fs*13 (n=11), R86W (n=10), and R113H (n=10). The prevalence of CD274 mutations varied depending on tumor type with diffuse large B-cell lymphoma (1.9%, 19/997), cutaneous squamous cell carcinoma (1.6%, 14/868), endometrial adenocarcinoma (1.0%, 36/3740), unknown primary melanoma (0.9%, 33/3679), and cutaneous melanoma (0.8%, 32/3874) having the highest frequency of mutations. Of the R260H cases concurrently tested with PD-L1 IHC, most (81.8%, 9/11) had no PD-L1 expression, which contrasts to the five E237K cases where most (80%, 4/5) had PD-L1 expression. In addition, we saw a significantly lower level of PD-L1 expression in samples with a clonal truncating variant (nonsense or frameshift indel) when compared with samples with a subclonal truncating variants (mean: TPS=1 vs TPS=38; p<0.001), and also in clonal versus subclonal missense mutations (mean: TPS=11 vs TPS=22, respectively; p=0.049)ConclusionsWe defined the landscape of CD274 mutations in a large cohort of tumor types that can be used as a reference for examining CD274 mutations as potential resistance biomarkers for ICPI. Furthermore, we presented novel data on the correlation of CD274 mutations and PD-L1 protein expression, providing important new information on the potential functionality of these mutations and can serve as a basis for future research.

scholarly journals Cancer Vaccines: Promising Therapeutics or an Unattainable Dream

Vaccines ◽  
2021 ◽  
Vol 9 (6) ◽  
pp. 668
Author(s):  
Howard Donninger ◽  
Chi Li ◽  
John W. Eaton ◽  
Kavitha Yaddanapudi
Keyword(s):  
Stem Cell ◽  
Immune System ◽  
Tumor Immunity ◽  
Cancer Vaccines ◽  
Tumor Antigens ◽  
Host Immune System ◽  
Tumor Type ◽  
Therapeutic Vaccines ◽  
Cancer Types ◽  
Prophylactic Vaccines

The advent of cancer immunotherapy has revolutionized the field of cancer treatment and offers cancer patients new hope. Although this therapy has proved highly successful for some patients, its efficacy is not all encompassing and several cancer types do not respond. Cancer vaccines offer an alternate approach to promote anti-tumor immunity that differ in their mode of action from antibody-based therapies. Cancer vaccines serve to balance the equilibrium of the crosstalk between the tumor cells and the host immune system. Recent advances in understanding the nature of tumor-mediated tolerogenicity and antigen presentation has aided in the identification of tumor antigens that have the potential to enhance anti-tumor immunity. Cancer vaccines can either be prophylactic (preventative) or therapeutic (curative). An exciting option for therapeutic vaccines is the emergence of personalized vaccines, which are tailor-made and specific for tumor type and individual patient. This review summarizes the current standing of the most promising vaccine strategies with respect to their development and clinical efficacy. We also discuss prospects for future development of stem cell-based prophylactic vaccines.

MRI analysis and surgical treatment of Wassel Type IV duplicated thumbs

2021 ◽  
pp. 175319342098321
Author(s):  
Anyuan Wang ◽  
Jian Ding ◽  
Long Wang ◽  
Tinggang Chu ◽  
Zhipeng Wu ◽  
...  
Keyword(s):  
Type A ◽  
Surgical Reconstruction ◽  
Mri Findings ◽  
Level Of Evidence ◽  
Type D ◽  
Type Iv ◽  
Secondary Operations ◽  
Type C

We present the MRI findings for 39 Wassel Type IV duplicated thumbs in 38 patients. We found that MRI revealed the morphology of the cartilaginous connection between the thumb anlages and the location of the deviation corresponding to the classification of Horii, which allowed precise preoperative planning of corrective osteotomies. All 39 thumbs were available for follow-up after surgical reconstruction at a mean of 29 months (range 25 to 39). Four out of nine Horii Type A cases and all 12 Type B, as well as the six Type C and the six Type D cases, achieved good results according to the Tada scoring system. Five Type A cases achieved fair results with residual stiffness of the interphalangeal joint. No secondary operations were needed. We conclude that MRI proved useful in subclassifying Wassel Type IV duplicated thumbs and may aid in planning the osteotomies needed for their reconstruction. Level of evidence: IV

Retrospective Analysis of the Prognostic Factors That Influence Treatment Response and Survival of Patients with Cancer of Unknown Primary

QJM ◽  
2021 ◽  
Vol 114 (Supplement_1) ◽  
Author(s):  
Zeinab Abdlelhafeez ◽  
Dina Ragab ◽  
Nervana Hussien ◽  
Fatma El – Tabakh
Keyword(s):  
Prognostic Factors ◽  
Treatment Response ◽  
Retrospective Analysis ◽  
Clinical Oncology ◽  
Cancer Registries ◽  
Cancer Of Unknown Primary ◽  
Response To Treatment ◽  
Unknown Primary ◽  
University Hospitals ◽  
Patients With Cancer

Abstract Background Cancers of unknown primary site (CUPs) are heterogeneous group of metastatic tumors for which a standardized diagnostic work-up could not recognize the site of origin at the time of diagnosis. Cancer registries around the world report the incidence of CUP in the range of 3%–5% of all malignancies, worldwide the overall age-standardized incidence per 100.000 people per year is 4–19 cases. CUP therefore ranks among the top 10 commonest malignancies. CUP occurs equally in both males and females, at average age 60 years old. Incidence of CUP in Egypt is 6.1%in males and 5.5% in females. Aim of the Work to retrospectively identify the prognostic factors that influence treatment outcome and survival of patients diagnosed with cancer of unknown primary treated patients at Clinical Oncology departments at Ain Shams University Hospitals (ASUH) and Helwan University Hospitals by retrospective analysis. Patients and Methods At the department of clinical oncology, Ain Shams University, 102 patients with cancer of unknown primary were identified in the period between January 2012 and December 2017, all patients data was collected and reviewed. The primary end point of this study is to identify different prognostic factors that influence treatment response and OS in 102 patients with CUP in the period from January 2012 to December 2017. Results Patients with PS 1, with no comorbidities showed better treatment response, also Patients younger than 65year, presented with PS1, with no comorbidity had longer survival. Conclusion CUP has a poor prognosis. Some prognostic factors that affect response to treatment and survival in these patients, which may be identified.

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