Predictive Biomarker For Development Research Articles

Biomarkers for therapy selection in metastatic urothelial cancer

The treatment of metastatic urothelial cancer (mUC) has been transformed by recent progress in clinical trials and drug development. There are now three therapeutic classes with proven benefits in mUC: chemotherapy, immunotherapy, and targeted therapy. The optimal sequence and combination of these classes remain to be defined. Biomarker development is essential to guide treatment selection at each therapeutic juncture. Two biomarkers, programmed death-ligand 1 expression and fibroblast growth factor receptor alterations, have been incorporated into the mUC treatment paradigm thus far. This review discusses predictive biomarkers in development and their potential to influence mUC treatment selection moving forward.

Somatosensory dysfunction in patients with posttraumatic headache: A systematic review.

Aim of the review is to summarize the knowledge about the sensory function and pain modulatory systems in posttraumatic headache and discuss its possible role in patients with posttraumatic headache. Posttraumatic headache is the most common complication after traumatic brain injury, and significantly impacts patients' quality of life. Even though it has a high prevalence, its origin and pathophysiology are poorly understood. Thereby, the existing treatment options are insufficient. Identifying its mechanisms can be an important step forward to develop target-based personalized treatment. We searched the PubMed database for studies examining pain modulation and/or quantitative sensory testing in individuals with headache after brain injury. The studies showed heterogenous alterations in sensory profiles (especially in heat and pressure pain perception) compared to healthy controls and headache-free traumatic brain injury-patients. Furthermore, pain inhibition capacity was found to be diminished in subjects with posttraumatic headache. Due to the small number of heterogenous studies a distinct sensory pattern for patients with posttraumatic headache could not be identified. Further research is needed to clarify the underlying mechanisms and biomarkers for prediction of development and persistence of posttraumatic headache.

Foveal crack sign as a predictive biomarker for development of macular hole in fellow eyes of patients with full-thickness macular holes

To investigate the prevalence and predictive value of the foveal crack sign (FCS) in fellow eyes of patients with full-thickness macular holes (FTMH) regarding future macular hole (MH) formation. In a retrospective observational case series, 113 fellow eyes of 113 patients with FTMH have been observed during a mean follow-up time of 21 months. According to baseline SD-OCT images, patients were divided into 4 separate groups: patients with FCS and vitreous adhesion, patients with FCS and vitreous detachment, patients without FCS with vitreous adhesion, patients without FCS with vitreous detachment. Progression rate to MH formation, predictive value of FCS and of vitreous interface status were calculated and compared across the four groups. FCS was observed in 19 of 113 fellow eyes (17%) of patients with FTMH, 10 of them with progression to MH during the mean follow up time of 21 months. 2 other eyes with progression to MH showed no FCS at baseline. Progression rate was shown to be 77% (10 of 13 eyes) in patients with FCS and vitreous adhesion, 0% (none of 6 eyes) in patients with FCS and vitreous detachment, 4% (2 of 48 eyes) in patients without FCS with vitreous adhesion, 0% (none of 46 eyes) in patients without FCS with vitreous detachment. FCS had sensitivity of 83.3% (95% CI 50.9–97.1%) and specificity of 91.1% (95% CI 83.3–95.6%) in predicting MH formation, positive predictive value of FCS was 52.6% (95% CI 29.5–74.8%) and negative predictive value 97.9% (95% CI 91.8–99.6%). Having simultaneously FCS and vitreous adhesion showed 83.3% (95% CI 50.9–97.1%) sensitivity and 97.1% (95% CI 91.1–99.2%) specificity in predicting macular hole formation; positive predictive value was 76.9% (95% CI 46.0–93.8%) and negative predictive value was 98.0% (95% CI 92.4–99.7%). Fellow eyes of patients with FTMH with foveal crack sign are at a very high risk (77%) of FTMH development, as long as posterior vitreous adhesion is present.

Exosomal miRNAs as circulating biomarkers for prediction of development of haematogenous metastasis after surgery for stage II/III gastric cancer.

Exosomes secreted by living cancer cells can regulate metastasis. Exosomal miRNAs can reflect pathological conditions of the original cancer cells. Therefore, we aim to identify exosomal miRNAs as circulating biomarkers for haematogenous metastasis of gastric cancer. Pre‐treatment serum samples of eighty‐nine patients with stage II/III gastric cancer were collected. Thirty‐four of them developed haematogenous metastasis after surgery and the other fifty‐five did not. Extraction of exosomes was validated by western blot, transmission electron microscopy and nanoparticle tracking analysis. MiRNA qPCR array was performed in three matched pairs of samples. Internal control was selected from PCR array and validated in the remaining samples. Expressions of exosomal miRNAs were evaluated in the remaining samples by RT‐qPCR, as well as in gastric cancer tissue samples and cell culture medium. Expression levels of exosomal miRNAs were analysed with clinical characteristics. The results indicated thirteen up‐regulated and six down‐regulated miRNAs were found after normalization. MiR‐379‐5p and miR‐410‐3p were significantly up‐regulated in metastatic patients (P < .01). Higher expression of exosomal miR‐379‐5p or miR‐410‐3p showed shorter progression‐free survival of the patients (P < .05). It was also found that miR‐379‐5p and miR‐410‐3p were down‐regulated in gastric cancer tissue samples, while they were significantly up‐regulated in gastric cancer cell culture medium compared with cancer cells. In conclusion, exosomal miRNAs are promising circulating biomarkers for prediction of development of haematogenous metastasis after surgery for stage II/III gastric cancer.

Inflammation in low back pain may be detected from the peripheral blood: suggestions for biomarker.

Biomarker for prediction of development of low back pain, and disease progression in chronic conditions are virtually non-existent. In the present study, we examined evidence of inflammation in the peripheral blood and demonstrated significant changes in neuroinflammation markers in subjects with chronic low back pain in comparison with control subjects. The present study was performed using peripheral blood from subjects with chronic low back pain and age-matched control subjects. Western blotting, real-time RT-PCR, cell culture and invitro assays were incorporated to perform the current study. We obtained evidence that the balance between proinflammatory and anti-inflammatory cytokines is misaligned, with decrease in interleukin-10 (IL-10) expression and increase in interleukin-6 (IL-6) expression. Furthermore, we demonstrated increase in CD16 monocyte expression. Cells were cultured under differential conditions to generate M1/M2 macrophages. In the macrophages, opioid secretory capacity was shown to be diminished. Finally, Dragon (repulsive guidance molecule b, RGMb) expression was shown diminished in M1 macrophages, which serves as a key transcriptional inhibitor of IL-6 expression. These biochemical and cellular alterations in chronic low back pain can serve as potential biomarkers for assessing disease initiation, intensity and progression.

Biomarkers in the pathogenesis, diagnosis, and treatment of psoriasis

Biomarkers in the pathogenesis, diagnosis, and treatment of psoriasis Silvia Molteni, Eva RealiLaboratory of Translational Immunology, Istituto Ortopedico Galeazzi, Milan, ItalyAbstract: Development of psoriasis results from a complex interplay between genetically predisposing factors and environmental triggers that give rise to a self-sustaining pathogenic cycle involving T cells, dendritic cells, connective tissue, and skin epithelium. From 5% to 40% of patients with psoriasis also develop psoriatic arthritis, and increasing evidence indicates an association with other systemic manifestations, including cardiovascular disease and the metabolic syndrome. In psoriatic disease, there is a need for development of biomarkers for assessment of disease severity, for prediction of the outcome of therapeutic interventions, and for distinction between the different clinical variants of the disease. A field of great importance is identification of biomarkers for prediction of development of comorbidities, such as arthritis, cardiovascular disease, and the metabolic syndrome. Genetic determinants of psoriasis and their products not only give an important insight into the pathogenesis of the disease, but may also function as markers of risk for developing cutaneous psoriasis or psoriatic arthritis. So far, there are limited validation data to support the use of candidate biomarkers in clinical practice. Here we review the data from several studies on some of the most promising candidate biomarkers for cutaneous psoriasis and psoriatic arthritis, for the detection of systemic inflammation, and for use as endpoints for therapeutic interventions. Attention is focused on the molecules that take part in the interplay giving rise to psoriasis and on gene products that may represent a link between predisposing genetic factors and the immune and inflammatory processes involved in pathogenesis of the disease. Finally, we provide an overview on how biomarkers can offer insights into the pathogenesis and natural history of psoriasis.Keywords: psoriatic disease, genetic markers, tissue-associated biomarkers, serum biomarkers, predictive factors, comorbidities

P-273 The role of Ki67, p53, EGFR, HER2 and CD31 as possible predictive biomarkers for development of lung cancer in a high-risk population

P-273 The role of Ki67, p53, EGFR, HER2 and CD31 as possible predictive biomarkers for development of lung cancer in a high-risk population