Baylor Research Institute

Kandimalla, R., H. Tomihara, J. K. Banwait, K. Yamamura, G. Singh, H. Baba and A. Goel (2020). “A 15-Gene Immune, Stromal, and Proliferation Gene Signature that Significantly Associates with Poor Survival in Patients with Pancreatic Ductal Adenocarcinoma.” Clin Cancer Res 26(14): 3641-3648.

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PURPOSE: Pancreatic ductal adenocarcinoma (PDAC) is a lethal disease with dismal survival rates. Tumor microenvironment (TME), comprising of immune cells and cancer-associated fibroblasts, plays a key role in driving poor prognosis and resistance to chemotherapy. Herein, we aimed to identify a TME-associated, risk-stratification gene biomarker signature in PDAC. EXPERIMENTAL DESIGN: The initial biomarker discovery was performed in The Cancer Genome Atlas (TCGA, n = 163) transcriptomic data. This was followed by independent validation of the gene signature in the International Cancer Genome Consortium (ICGC, n = 95), E-MTAB-6134 (n = 288), and GSE71729 (n = 123) datasets for predicting overall survival (OS), and for its ability to detect poor molecular subtypes. Clinical validation and nomogram establishment was undertaken by performing multivariate Cox regression analysis. RESULTS: Our biomarker discovery effort identified a 15-gene immune, stromal, and proliferation (ISP) gene signature that significantly associated with poor OS [HR, 3.90; 95% confidence interval (CI), 2.36-6.41; P < 0.0001]. This signature also robustly predicted survival in three independent validation cohorts ICGC [HR, 2.63 (1.56-4.41); P < 0.0001], E-MTAB-6134 [HR, 1.53 (1.14-2.04); P = 0.004], and GSE71729 [HR, 2.33 (1.49-3.63); P < 0.0001]. Interestingly, the ISP signature also permitted identification of poor molecular PDAC subtypes with excellent accuracy in all four cohorts; TCGA (AUC = 0.94), ICGC (AUC = 0.91), E-MTAB-6134 (AUC = 0.80), and GSE71729 (AUC = 0.83). The ISP-derived high-risk patients exhibited significantly poor OS in a clinical validation cohort [n = 119; HR, 2.62 (1.50-4.56); P = 0.0004]. A nomogram was established which included the ISP, CA19-9, and T- and N-stage for eventual clinical translation. CONCLUSIONS: We report a novel gene signature for risk-stratification and robust identification of patients with PDAC with poor molecular subtypes.

Guerrero-Miranda, C. Y. and S. A. Hall (2020). “Rethinking the Future with Evolving Technology: It’s Time to Empower Change in Heart Transplantation.” Am J Transplant 2020 Jul 27. [Epub ahead of print.].

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According to the National Institutes of Health (NIH) Biomarker Definition Working Group, biomarkers are characteristics objectively measured and indicators of a physiologic or pathologic process. In 1847, the first cancer biomarker was discovered when the Bence Jones proteins were found in the urine of patients with Multiple Myeloma; since then, biomarkers have played a crucial role in modern medicine. An ideal biomarker should be non-invasive, low cost, quantifiable, consistent across ethnic and gender groups, and reflect correlation in different diseases or conditions.

Rinchai, D., B. Syed Ahamed Kabeer, M. Toufiq, Z. Tatari-Calderone, S. Deola, T. Brummaier, M. Garand, R. Branco, N. Baldwin, M. Alfaki, M. C. Altman, A. Ballestrero, M. Bassetti, G. Zoppoli, A. De Maria, B. Tang, D. Bedognetti and D. Chaussabel (2020). “A modular framework for the development of targeted Covid-19 blood transcript profiling panels.” J Transl Med 18(1): 291.

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BACKGROUND: Covid-19 morbidity and mortality are associated with a dysregulated immune response. Tools are needed to enhance existing immune profiling capabilities in affected patients. Here we aimed to develop an approach to support the design of targeted blood transcriptome panels for profiling the immune response to SARS-CoV-2 infection. METHODS: We designed a pool of candidates based on a pre-existing and well-characterized repertoire of blood transcriptional modules. Available Covid-19 blood transcriptome data was also used to guide this process. Further selection steps relied on expert curation. Additionally, we developed several custom web applications to support the evaluation of candidates. RESULTS: As a proof of principle, we designed three targeted blood transcript panels, each with a different translational connotation: immunological relevance, therapeutic development relevance and SARS biology relevance. CONCLUSION: Altogether the work presented here may contribute to the future expansion of immune profiling capabilities via targeted profiling of blood transcript abundance in Covid-19 patients.

Mistry, P., M. Balwani, D. Barbouth, T. A. Burrow, E. I. Ginns, O. Goker-Alpan, G. A. Grabowski, R. V. Kartha, P. S. Kishnani, H. Lau, C. U. Lee, G. Lopez, G. Maegawa, S. Packman, C. Prada, B. Rosenbloom, T. R. Lal, R. Schiffmann, N. Weinreb and E. Sidransky (2020). “Gaucher disease and SARS-CoV-2 infection: Emerging management challenges.” Mol Genet Metab 130(3): 164-169.

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Effective treatments for Gaucher disease are available that successfully reverse many of the systemic non-neurological manifestations of the disease. Administration of the two therapies, enzyme replacement therapy (ERT) and therapy preventing substrate accumulation (SRT) (for GD1) are widely used. Each has specific considerations that may be impacted by aspects of the COVID-19 pandemic. [No abstract available; excerpt from article.].

Van Nguyen, H., M. Van Hoang, A. T. M. Dao, H. L. Nguyen, T. Van Nguyen, P. T. Nguyen, L. Q. Khuong, P. M. Le and S. Gilmour (2020). “An adaptive model of health system organization and responses helped Vietnam to successfully halt the Covid-19 pandemic: What lessons can be learned from a resource-constrained country.” Int J Health Plann Manage Jun 18. [Epub ahead of print.].

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Coping with the COVID-19 pandemic has been painful and no single model for such a purpose is perfect. However, sharing experiences is the best way for countries to learn real-time lessons and adapt to this rapidly changing pandemic. This commentary shares with the international community how an adaptive model of health system organization and responses helped Vietnam to break transmission of coronavirus. We find that an effective model is adaptive to time and context, and mobilizes and engages the wider society. We identify merging of different health system units into Center for Diseases Controls as a health system organization that saved massive resources. The early establishment of a formal committee responding to the pandemic helped unify every public health strategy. The mobilization of different stakeholders and communities added resources and facilitated a synchronous implementation of response strategies, even where those strategies involved significant personal or financial sacrifice. National training on Covid-19 treatment for healthcare professionals across the entire hospital system was useful to expand the health service availability. Quickly published response guidelines helped to activate every level of the health system and involve every sector of society. A strategy of keeping high alert and preemptive action is also essential for coping with the pandemic.