Semi-Supervised Methods to Predict Patient Survival from Gene Expression Data

An important goal of DNA microarray research is to develop tools to diagnose cancer more accurately based on the genetic profile of a tumor. There are several existing techniques in the literature for performing this type of diagnosis. Unfortunately, most of these techniques assume that different subtypes of cancer are already known to exist. Their utility is limited when such subtypes have not been previously identified. Although methods for identifying such subtypes exist, these methods do not work well for all datasets. It would be desirable to develop a procedure to find such subtypes that is applicable in a wide variety of circumstances. Even if no information is known about possible subtypes of a certain form of cancer, clinical information about the patients, such as their survival time, is often available. In this study, we develop some procedures that utilize both the gene expression data and the clinical data to identify subtypes of cancer and use this knowledge to diagnose future patients. These procedures were successfully applied to several publicly available datasets. We present diagnostic procedures that accurately predict the survival of future patients based on the gene expression profile and survival times of previous patients. This has the potential to be a powerful tool for diagnosing and treating cancer

Comparison of referring and final pathology for patients with T‐cell lymphoma in the National Comprehensive Cancer Network

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/107537/1/cncr28676.pd

The standardization of immunohistochemical detection and interpretation of CD30 expression in lymphomas

CD30 can be expressed in a variety of lymphoma subtypes, among which classical Hodgkin lymphoma (CHL) and anaplastic large cell lymphoma (ALCL) are the most common ones. Recently, Brentuximab vedotin, the antibody-drug conjugate targeting CD30, has been approved in the treatment of patients with refractory and relapsed CHL and ALCL, and has achieved significant curative effect. However, whether CD30-targeted therapy could benefit patients with other types of lymphoma remains largely unknown. Accurate evaluation of the expression level of CD30 may thus have important guiding significance for the clinical trials and individualized treatment of patients with those lymphomas. To date, CD30 detection is mainly via immunohistochemical staining, however, with no unified and standardized process and interpretation method. We herein described the current status on CD30 testing, and explored the procedures of immunohistochemical detection and interpretation of the results through multicentric studies. A consensus was finally reached, which was based on the combination of our research results, literature review, experts’ experience, and internal discussion among the panel members, and might hopefully contribute to standardization of the immunohistochemical detection and interpretation of CD30 expression in lymphomas

Genetic Immunization with CDR3-Based Fusion Vaccine Confers Protection and Long-Term Tumor-Free Survival in a Mouse Model of Lymphoma

Therapeutic vaccination against idiotype is a promising strategy for immunotherapy of B-cell malignancies. We have previously shown that CDR3-based DNA immunization can induce immune response against lymphoma and explored this strategy to provide protection in a murine B-cell lymphoma model. Here we performed vaccination employing as immunogen a naked DNA fusion product. The DNA vaccine was generated following fusion of a sequence derived from tetanus toxin fragment C to the VHCDR3109−116 epitope. Induction of tumor-specific immunity as well as ability to inhibit growth of the aggressive 38C13 lymphoma and to prolong survival of vaccinated mice has been tested. We determined that DNA fusion vaccine induced immune response, elicited a strong protective antitumor immunity, and ensured almost complete long-term tumor-free survival of vaccinated mice. Our results show that CDR3-based DNA fusion vaccines hold promise for vaccination against lymphoma

Primary cutaneous B-cell lymphoblastic lymphoma in an elderly man

Precursor B-cell lymphoblastic lymphoma (B-LBL) is an uncommon high-grade neoplasm of immature B cells. It occurs predominantly in childhood with extranodal involvement such as skin and bone. Therefore, primary cutaneous involvement in elderly adults is a very rare manifestation of B-LBL. Here, we report a 78-year-old man with B-LBL presenting as a single cutaneous lesion which was immunohistochemically positive for leukocyte common antigen (LCA), CD79a, paired box 5 (PAX5), B cell lymphoma-2 (bcl-2), and terminal deoxynucleotidyl transferase (TdT) staining, but was without systemic involvement. The patient was treated using cyclophosphamide, adriamycin, vincristine, and prednisolone (CHOP), and achieved complete response (CR) at the first response assessment conducted after 3 CHOP cycles. After an additional cycle of CHOP treatment, radiotherapy was administered at a total dose of 3,600 cGy over 4 weeks. At the 21-month follow-up, he had maintained CR

Spanish Lymphoma Group (GELTAMO) guidelines for the diagnosis, staging, treatment, and follow-up of diffuse large B-cell lymphoma

Diffuse large B-cell lymphoma (DLBCL) accounts for approximately 30% of non-Hodgkin lymphoma (NHL) cases in adult series. DLBCL is characterized by marked clinical and biological heterogeneity, encompassing up to 16 distinct clinicopathological entities. While current treatments are effective in 60% to 70% of patients, those who are resistant to treatment continue to die from this disease. An expert panel performed a systematic review of all data on the diagnosis, prognosis, and treatment of DLBCL published in PubMed, EMBASE and MEDLINE up to December 2017. Recommendations were classified in accordance with the Grading of Recommendations Assessment Development and Evaluation (GRADE) framework, and the proposed recommendations incorporated into practical algorithms. Initial discussions between experts began in March 2016, and a final consensus was reached in November 2017. The final document was reviewed by all authors in February 2018 and by the Scientific Committee of the Spanish Lymphoma Group GELTAMO

Data Mining Approaches to Diffuse Large B–Cell Lymphoma Gene Expression Data Interpretation

This paper presents a comprehensive study of gene expression patterns originating from a diffuse large B–cell lymphoma (DLBCL) database. It focuses on the implementation of feature selection and classification techniques. Thus, it firstly tackles the identification of relevant genes for the prediction of DLBCL types. It also allows the determination of key biomarkers to differentiate two subtypes of DLBCL samples: Activated B–Like and Germinal Centre B–Like DLBCL. Decision trees provide knowledge–based models to predict types and subtypes of DLBCL. This research suggests that the data may be insufficient to accurately predict DLBCL types or even detect functionally relevant genes. However, these methods represent reliable and understandable tools to start thinking about possible interesting non–linear interdependencies

mRNA in exosomas as a liquid biopsy in non-Hodgkin Lymphoma: a multicentric study by the Spanish Lymphoma Oncology Group

Purpose: To determine the feasibility of mRNAs (C-MYC, BCL-XL, BCL-6, NF-κβ, PTEN and AKT) in exosomes of plasma as a liquid biopsy method for monitoring and prognostic evolution in B-cell lymphomas. Patients and Methods: Exosomes were isolated from 98 patients with B-cell Lymphoma and 68 healthy controls. mRNAs were analyzed by quantitative PCR. An additional 31 post-treatment samples were also studied. Results: In the general and follicular lymphoma series, the presence of AKT mRNA was associated with poor response to rituximab-based treatment. Patients with first relapse or disease progression showed a lower percentage of PTEN and BCL-XL mRNA. The presence of BCL-6 mRNA was associated with a high death rate. The absence of PTEN mRNA in the general series, and presence of C-MYC mRNA in follicular lymphomas, were associated with short progression-free survival. BCL-6 and C-MYC mRNA were independent prognostic variables of overall survival. C-MYC mRNA may provide prognostic information with respect to overall survival. BCL-XL mRNA and increase of BCL-6 mRNA in post-treatment samples could serve as molecular monitoring markers. Conclusions: This is the first large study to evaluate the prognostic and predictive values of pretreatment tumor-associated mRNA in exosomes. BCL-6 and C-MYC mRNA positivity in pretreatment samples were predictors of worse PFS compared to patients with mRNA negativity. C-MYC mRNA positivity was also a statistically significant predictor of inability to obtain complete response with first-line therapyThis study was supported by grants FIS-PI08/0862, and SAF2010-20750. During this study, V. García received Fundación AECC and RTICC-RD2012/0036/0006 fellowship