Multiple Myeloma in the Black Community – Everyday Health

For many Black Americans with multiple myeloma, socioeconomic status can stand in the way of even standard care, especially for those who live in rural areas, according to Calloway-Campbell.

Youre not close to an academic center, she says. And local doctors may not have even heard of multiple myeloma. Getting to a doctor can be near-impossible for people who dont have a car or other means of transportation, as well, and even gathering information can be challenging without easy access to Wi-Fi.

Treatment for myeloma is exorbitantly expensive too. According to a study published in JAMA Open Network in July 2021, the average lifetime cost of treating multiple myeloma was upwards of $185,000 an intimidating price tag for most people, much less for those who may be unemployed or underpaid, lacking health insurance, or inadequately covered.

The National Cancer Institute (NCI)reports that while 67 percent of white Americans under 65 and 44 percent over 65 have private health insurance, only 51 percent of African Americans under 65 and 28 percent over 65 are insured. And private health insurance is key to quality myeloma care.

According to the NCI, for instance, non-white recipients of Medicaid or Medicare are less likely to be prescribed new drugs or treated with stem cell transplants compared to non-white patients who have private insurance. This is significant, given a quarter of Medicare and Medicare Advantage recipients are African American.

Financial assistance for myeloma treatment is available though. On the IMF websites Financial Assistance page, for instance, are a list of options ranging from small stipends, which can be put directly toward treatment, to sources of help for non-medical expenses, such as transportation and childcare. The organization also has a page with information about drug reimbursement and help with copays.

Other sources for financial aid for people of all ethnicities living with multiple myeloma include:

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Multiple Myeloma in the Black Community - Everyday Health

Diamyd Medical partners with JDRF to advance the DIAGNODE-3 … – PR Newswire

STOCKHOLM, April 4, 2023 /PRNewswire/ -- Diamyd Medical and JDRF, the leading global type 1 diabetes research and advocacy organization, have entered into a four-year research and development collaboration including a non-dilutive $5 million award to Diamyd Medical to support its ongoing Phase 3 trial with the precision medicine antigen-specific immunotherapy Diamyd. The grant will be funded under JDRF's Industry Discovery & Development Partnerships program that focuses on commercialization of therapeutics and devices for the treatment, cure, and prevention of type 1 diabetes and its complications.

"We could not have a better partner than JDRF as we are focusing on rapid advancement of our antigen-specific immunotherapy towards the market," said Ulf Hannelius, CEO of Diamyd Medical. "We expect this collaboration to significantly boost patient recruitment to this international study as well as our commercial preparations."

"JDRF is committed to supporting and advancing disease modifying therapies to delay and reverse type 1 diabetes," said Sanjoy Dutta, Ph.D., chief scientific officer at JDRF. "We are excited about Diamyd Medical's groundbreaking Phase 3 trial and its potential advancements in the preservation of insulin production for people recently diagnosed with type 1 diabetes."

"JDRF has played a crucial role in many of the most novel therapeutics and devices that have been approved in the field for those with type 1 diabetes," said Mark Atkinson, Ph.D., director of the Diabetes Institute at the University of Florida and Diamyd Medical Board Member. "JDRF's commitment to this Phase 3 program is a validation of the scientific and clinical value of the antigen-specific immunotherapy Diamyd. It also emphasizes the importance of making disease modifying therapies available to everyone affected by this disease."

About Diamyd MedicalDiamyd Medical develops precision medicine therapies for Type 1 Diabetes. Diamyd is an antigen-specific immunotherapy for the preservation of endogenous insulin production. DIAGNODE-3, a confirmatory Phase III trial is actively recruting patients with recent-onset Type 1 Diabetes in eight European countries and is being preparedto start recruiting patients in the US this summer. Significant results have previously been shown in a large genetically predefined patient group in a large-scale meta-analysis as well as in the Company's European Phase IIb trial DIAGNODE-2, where the Diamyd was administered directly into a lymph node in children and young adults with recently diagnosed Type 1 Diabetes. A biomanufacturing facility is being set up in Ume for the manufacture of recombinant GAD65, the active ingredient in the antigen-specific immunotherapy Diamyd. Diamyd Medical also develops the GABA-based investigational drug Remygen as a therapy for regeneration of endogenous insulin production and to improve hormonal response to hypoglycaemia. An investigator-initiated Remygen trial in individuals living with Type 1 Diabetes for more than five years is ongoing at Uppsala University Hospital. Diamyd Medical is one of the major shareholders in the stem cell company NextCell Pharma AB as well as in the artificial intelligence company MainlyAI AB.

Diamyd Medical's B-share is traded on Nasdaq First North Growth Market under the ticker DMYD B. FNCA Sweden AB is the Company's Certified Adviser.

About JDRF JDRF's mission is to accelerate life-changing breakthroughs to cure, prevent and treat T1D and its complications. To accomplish this, JDRF has invested more than $2.5 billion in research funding since our inception. We are an organization built on a grassroots model of people connecting in their local communities, collaborating regionally and globally for efficiency and broader fundraising impact, and uniting on a global stage to pool resources, passion, and energy. We collaborate with academic institutions, policymakers, and corporate and industry partners to develop and deliver a pipeline of innovative therapies to people living with T1D. Our staff and volunteers throughout the United States and our five international affiliates are dedicated to advocacy, community engagement, and our vision of a world without T1D. For more information, please visit jdrf.org or follow us on Twitter (@JDRF), Facebook (@myjdrf), and Instagram (@jdrfhq).

About Type 1 Diabetes Type 1 diabetes is an autoimmune condition that causes the pancreas to make very little insulin or none at all. This leads to dependence on insulin therapy and the risk of short or long-term complications, which can include highs and lows in blood sugar; damage to the kidneys, eyes, nerves, and heart; and even death if left untreated. Globally, it impacts nearly 9 million people. Many believe T1D is only diagnosed in childhood and adolescence, but diagnosis in adulthood is common and accounts for nearly 50% of all T1D diagnoses. The onset of T1D has nothing to do with diet or lifestyle. While its causes are not yet entirely understood, scientists believe that both genetic factors and environmental triggers are involved. There is currently no cure for T1D.

For further information, please contact:Ulf Hannelius, President and CEOPhone: +46 736 35 42 41E-mail: [emailprotected]

The following files are available for download:

SOURCE Diamyd Medical AB

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Diamyd Medical partners with JDRF to advance the DIAGNODE-3 ... - PR Newswire

Rejuvenation Roundup March 2023 – Lifespan.io News

March marks the beginning of spring and the time for renewal, and this month, labs around the world have looked into renewing older concepts of aging and discovered potential methods for renewing our bodies.

Partnership Opportunities for the 5th Annual Age-Related Disease Therapeutics Summit: This conference is seeking partners who want to showcase their companies to biotechnology and investment leaders, listing contract research, biomarkers of aging, epigenetics, and preclinical services as the preferred areas of interest.

Thank you to OneSkin, one of our philanthropic partners who has generously agreed to donate a percentage of their monthly revenue to Lifespan.io, to support our mission of longevity biotechnology advocacy and education.

OneSkin is a longevity company developing products designed to extend skin and body health by targeting aging at its source.

Team and activities

Rep. Bilirakis on the Longevity Science Caucus: We in the longevity field have received powerful allies on Capitol Hill with the creation of the bipartisan Congressional Caucus for Longevity Science. We had the opportunity to ask questions of one of its co-chairs.

Lifespan News

Human Brain Organoids in Rats: Emmett Short talks about how human neurons in rat brains can actually fulfill critical functions in these animals.

NAD+, Fat, and Muscle: On this episode, Emmett Short goes over a new study showing that nicotinamide riboside (NR) increases both fat and muscle.

Best Time to Exercise: This episode features some rather surprising results gleaned from examining the effects of regular morning exercise on UK Biobank participants.

Protein and Muscle: This Lifespan News is on a study showing that diets with less protein are connected to better muscle maintenance with aging.

Exercise and Supplements: Emmett Short talks about a recent meta-study of exercise and supplements, which showed inconclusive results despite its large dataset.

Young Blood for Brain Boosting: This episode discusses a study showing that the brains of old mice benefit by receiving the blood of young mice.

Prof. Tzipi Strauss on the Upcoming Longevity Center: In Sheba Medical Center in Israel, the first-of-its-kind Longevity Center will soon open its doors. We spoke with its future director, Prof. Tzipi Strauss, who is also leading the Department of Neonatology at Sheba.

Prof. George Church on Cellular Reprogramming and Longevity: Professor of Genetics at Harvard Medical School, a veteran geroscientist, and a serial entrepreneur, George Church hardly needs an introduction. While we are always happy to discuss the present and future of geroscience with him, this interview focuses on the two gene therapy papers that he recently co-authored.

Ashley Zehnder on Harnessing Animal Genes Against Aging: Many species have developed amazing mechanisms to cope with various drivers of aging. A handful of bold entrepreneurs are trying to go commercial, and one of them is Ashley Zehnder, DVM, PhD, co-founder and CEO of Fauna Bio, a biotech startup that looks for protective genotypes in animals in order to weaponize them against human diseases.

Ryan OShea of Future Grind hosts this months podcast, showcasing the events and research discussed here.

Human Fasting Modulates Macrophage Function: This month, Dr. Oliver Medvedik explored a recent study that looked at the effects of prolonged fasting on human macrophages and how metabolites from that fasting increased median lifespan in Caenorhabditis elegans.

Insider Insight: Meet the Organizers of LongHack: LongHack, the longevity hackathon hosted by DeSci organization VitaDAO, was held on January 20th-23rd, 2023. Gathering researchers, developers, and other interested parties to create new tools and solutions for longevity, ten teams competed to impress the judging panel and take home prizes.

A Lasting Rise in Investment in the Longevity Sector: 2021 marked one of the biggest years in longevity financing, with 2022 following closely behind. Over the past ten years, the industry has grown in financing from $500 million in 2013 to a peak of $6.2 billion in 2021.

Dr. Nir Barzilai on How to Age Later: In Age Later: Healthspan, Lifespan, and the New Science of Longevity, Dr. Nir Barzilai provides an insightful and comprehensive overview of the latest research on aging and longevity.

Research Roundup

Association Between BMI and Mortality Revisited: Ryan K. Masters, professor at CU Boulder, suggests that when adjusted for body shape and lifelong shifts, the relationship between BMI and mortality is more linear and robust than previously thought, with normal BMI being the healthiest.

Exercise and Supplements Against Age-Related Inflammation: In a new systematic review, researchers have shown that combining some dietary supplements and exercise might be beneficial for people over the age of 60.

How NAD+ Relates to Smell Loss with Age: Researchers publishing in Aging Cell have elucidated a relationship between aging, the loss of smell, and NAD+ in a mouse model. Roughly half of people over the age of 65 experience a decreased ability to smell, and research has shown that it is an early biomarker for neurodegenerative diseases.

Extracellular Vesicles as a Hallmark of Aging: A review paper published in Cells has described multiple ways in which the secretion of extracellular vesicles changes with aging, leading the authors to propose it as its own hallmark.

New Small Molecule Alleviates Alzheimers in Mouse Model: Scientists have developed a custom-made molecule that targets a post-translationally modified kinase linked to Alzheimers, improving symptoms in a murine model of the disease.

Metformin and Rapamycin Rejuvenate Stem Cells in Mice: In a new study published in Aging Cell, researchers have shown that two promising anti-aging agents, the antibiotic rapamycin and the anti-diabetic drug metformin, reverse aging in a population of intestinal stem cells.

Young Blood Alters Gene Expression in Old Brain Cells: Research published in Nature Aging has shown that heterochronic parabiosis, the circulatory joining of young and old organisms, has rejuvenative effects on the gene expression of multiple types of brain cells in mice.

New Treatment Alleviates Depression Symptoms in Mice: Scientists have shown that the protein GDF11 can reverse depression-like symptoms in naturally aged mice and in a mouse model of depression.

Mitochondria, DNA, and Oxidative Stress: A paper published in Experimental Gerontology has provided a fresh and detailed look at the effects of oxidative stress on longevity. The free radical theory of aging, which purports that reactive oxygen species (ROS) are the core driver of aging, was developed all the way back in 1956.

Epigenetic Biomarker for Measuring Aging Through Fitness: A new biomarker for measuring biological aging based on physical fitness has been published in Aging, and it has been found to be useful in predicting health issues.

Excessive Fat, Not Sugar, Leads to Obesity in Mice: In a new study published in Endocrinology and Metabolism, researchers have shown that fat rather than sugar is the macronutrient that drives obesity and other detrimental metabolic changes if it constitutes a large proportion of dietary calories.

Inflammation Strongly Predicts Mortality After Statin Use: Analyzing data from three clinical trials, scientists have shown that excessive inflammation is a much stronger predictor of cardiovascular and all-cause mortality in patients on statins than excessive LDL cholesterol levels.

Sleep Apnea and Inflammatory Biomarkers of Tooth Decay: A study published in Heliyon has explained a relationship between sleep apnea and an increase of inflammatory factors in the mouth that are connected to the gum disease peridontitis.

The Human Cost of Metabolic Diseases: A new paper published in Cell Metabolism has shown the growing influence of metabolic diseases in an aging population. Metabolic diseases include hypertension, type 2 diabetes, hyperlipidemia, obesity, and non-alcoholic fatty liver disease.

Mediterranean Diet Might Lower Risk of Dementia: In a large-scale observational study, British scientists have shown that high levels of adherence to the Mediterranean diet might substantially lower the risk of dementia. The Mediterranean diet, is based on ingredients such as olive oil, vegetables, legumes, fish, and whole grains.

Vital Muscle Enzyme Declines With Aging: Research published in Nature Metabolism has described PCYT2, an enzyme essential for muscle function, and how it declines with aging. A necessary lipid synthesizer in muscle Human beings need PCYT2 as part of the Kennedy pathway to synthesize two critical components of the phosopholipid membrane that surrounds cells.

Long-Term Resistance Exercise Increases Autophagy: In a new systemic review published in Autophagy Reports, researchers have demonstrated that exercise plays a role in regulating autophagy, depending on its type. Autophagy is the way cells break down misbehaving or nonfunctional organelles and proteins in the cell.

Promoting Muscle Regeneration With an Immune Factor: A paper published today in Nature Aging has shown that a macrophage-regulating factor has a significant impact on muscle regeneration.

Vesicles from Senescent Cells Encourage Young Stem Cells: Scientists have shown that extracellular vesicles derived from senescent stem cells can improve the proliferation, viability, and migration capacity of healthy stem cells.

Senescent Cells and Loose Teeth: A team of researchers has recently published a study on the effects of senescence on periodontal tissues, which hold teeth to bone, in Aging.

Inhibiting DREAM for Enhanced DNA Damage Repair: In a new study published in Nature Structural and Molecular Biology, researchers have demonstrated that by manipulating the DREAM protein complex, a major regulator of DNA damage response, it might be possible to alter the number of DNA mutations accumulated with age.

Using AI to Measure Age Through the Eyes: An accepted manuscript in eLife Sciences has described eyeAge, a new clock that uses deep learning to analyze the eye in detail in order to predict chronological age and age acceleration.

Daily Step Count, Less Mortality, Diminishing Returns: A new study using wearable accelerometers suggests that you dont have to clock extreme numbers of steps every day to stay healthy.

Associations of sleeping, sedentary and physical activity with phenotypic age acceleration: Sedentary behavior was positively associated with aging. Replacing sedentary behaviors with walking/bicycling or moderate to vigorous physical activity was adversely associated with aging among adults.

Coenzyme Q10 supplementation improves the motor function of middle-aged mice by restoring the neuronal activity of the motor cortex: This study shows that CoQ10 improves brain mitochondrial function and physical performance in mice.

Increased SIRT1 Concentration Following Four Years of Selenium and Q10 Intervention Associated with Reduced Cardiovascular Mortality at 10-Year Follow-Up: This study suggests that this combination increases SIRT1 in a way that helps to prevent vascular aging.

Dietary magnesium intake is related to larger brain volumes and lower white matter lesions with notable sex differences: Higher dietary magnesium intake has been found to be associated with better brain health in the general population, particularly women.

Potential reversal of biological age in women following an 8-week methylation-supportive diet and lifestyle program: There was a statistically significant (p=.039) difference in the participants mean biological age before (55.83 years) and after (51.23 years) the 8-week diet and lifestyle intervention, with an average decrease of 4.60 years.

Six-Month Synbio Administration Affects Nutritional and Inflammatory Parameters of Older Adults: The PROBIOSENIOR project demonstrated how SYNBIO supplementation may positively influence some nutritional and inflammatory parameters in the elderly.

Mendelian randomization analyses reveal causal relationships between the human microbiome and longevity: These findings strongly implicate that these commensal microbes play a role in human longevity and suggest that they should be monitored to promote longevity.

AAV1.NT-3 gene therapy prevents age-related sarcopenia: The researchers reported functional, in vivo muscle physiology improvements

Transcriptional activation of endogenous Oct4 via the CRISPR/dCas9 activator ameliorates Hutchinson-Gilford progeria syndrome in mice: These results suggest that partial rejuvenation by activating this Yamanaka factor can be used as a novel strategy in treating geriatric diseases.

Ageing as a software design flaw: Well-known aging researcher Joo Pedro de Magalhes expands on the idea that aging is the result of misguided genetic programming rather than entropic damage.

Necroptosis inhibition counteracts neurodegeneration, memory decline, and key hallmarks of aging, promoting brain rejuvenation: These results demonstrate that necroptosis, which mediates degeneration of injured axons, contributes to age-dependent brain degeneration.

Effect of peripheral cellular senescence on brain aging and cognitive decline: Preserved cognition was associated with the removal of peripheral senescent cells, which decreased the systemic inflammation that normally drives neuroinflammation, BBB breakdown, and impaired synaptic function.

Immunotherapeutic approach to reduce senescent cells and alleviate senescence-associated secretory phenotype in mice: These results show that HCW9218 represents a novel immunotherapeutic approach and a clinically promising new class of senotherapeutic agents targeting cellular senescence-associated diseases.

The Fifth Annual Age-Related Disease Therapeutics Summit: The Age-Related Disease Therapeutics Summit will once again be held in San Francisco this year, and Lifespan.io readers are encouraged to use the code 32026Lifespan when signing up.

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Rejuvenation Roundup March 2023 - Lifespan.io News

Comprehensive proteomics and platform validation of urinary … – BMC Medicine

Research over the past several years has uncovered potentially important urine biomarkers and tests for BC, including BTA and NMP22. BTA-stat, an FDA-approved urine biomarker, is used clinically to detect bladder tumor-associated antigen (human complement factor H-related protein) in the urine. A meta-analysis of BTA stat reported a specificity of 67% and a sensitivity of 75% after reviewing 13 studies [8]. The sensitivity levels of BTA-stat have been shown to positively correlate with increasing grade of BC [8]. However, BTA-stat has several limitations. These include lower specificity values and issues relating to false-positive results in benign conditions [6]. Hence, urine BTA-stat may have limitations in the diagnosis and monitoring of disease progression. Similarly, NNP22 is an FDA-approved urine biomarker designed to detect the NMP22 protein levels which are high due to cell turnover from tumor apoptosis. A meta-analysis of 19 studies has identified this marker to have a pooled specificity of 88% and a sensitivity of 56% [7].

As opposed to studies looking at an isolated protein in the urine, a few screens have been reported where multiple proteins were examined simultaneously. Summarized below are a couple of studies documenting biomarkers with both sensitivity and specificity values greater than or equal to 85%. Goodison et al. performed a validation study for the urinary concentrations of 14 proteins (A1AT, APOE, ANG, CA9, CCL18, CD44, IL-8, MMP-9, MMP-10, OPN, PAI-1, PTX3, SDC1, and VEGF) using an ELISA [30]. An 8-biomarker panel (ANG, APOE, CA-9, IL-8, MMP-9, MMP-10, PAI-1, and VEGF) achieved the most accurate BC diagnosis with a sensitivity of 92% and a specificity of 97%. However, a panel of 3 biomarkers (APOE, IL-8, and VEGF) also performed well with a sensitivity of 90% and a specificity of 97% for the detection of BC [30]. Kumar et al. identified a 5-biomarker panel consisting of Apolipoprotein A4, Coronin-1A, DJ-1/PARK7, Gamma synuclein, and Semenogelin-2. ELISA and western blot data obtained an AUC of 0.92 and 0.98, respectively, in diagnosing Ta/T1 BC (sensitivity 79.2% and 93.9% for ELISA; specificity 100% and 96.7% for western blot) [31]. For the diagnosis of T2/T3 BC, the panel of markers achieved an AUC of 0.94 and 1, respectively, using the same methods (sensitivity 86.4% and 100%; specificity 100%) [31].

Low-grade BC has a high recurrence rate; therefore, identifying biomarkers for the surveillance of BC is essential for the potential clinical management of the disease. Rosser et al. identified 10 biomarkers (ANG, APOE, CA9, IL-8, MMP-9, MMP-10, SDC1, SERPINA1, SERPINE1, and VEFGA) using ELISA for monitoring urine for recurrent BC. The complete panel achieved an AUC of 0.90, a sensitivity of 79%, and a specificity of 88% [32]. De Paoli et al. identified a panel of 6 biomarkers (cadherin-1, EN2, ErbB2, IL-6, IL-8, and VEGF-A) and three clinical parameters including BCG therapies, stage at the time of diagnosis, and past recurrences. The panel achieved an AUC of 0.91 and was identified through microarray and ELISA analysis [33].

There are several reasons to discriminate patients with bladder cancer from benign conditions. In patients with hematuria, it would be helpful to identify who needs cystoscopic evaluation which is invasive. Given that urine proteins are easily measurable and are compatible with point-of-care monitoring, a quick urine test could dramatically impact triage and workflow in urology outpatient clinics. Likewise, in bladder cancer surveillance, a reliable urine biomarker can help determine if cancer (like CIS) was missed or to avoid cystoscopy in marker-negative patients. Similarly, urine biomarkers that can reliably distinguish MIBC from NMIBC can inform us as to who has the more aggressive disease. When used as a routine point-of-care test (either at home or at outpatient visits), these urinary biomarkers may facilitate earlier identification of aggressive disease and design of tailored therapy.

The present work represents the first attempt to screen>1000 urine proteins for urine biomarker candidates in BC, using a relatively novel aptamer-based screen. Systems biology analysis implicated molecular functions related to the extracellular matrix, collagen, integrin, heparin, and transmembrane tyrosine kinase signaling in BC susceptibility, with HNF4A and NFKB1 being key regulators. STEM analysis of the dysregulated pathways implicated a functional role for the immune system, complement, and interleukins in BC disease progression (Fig.3D). This study has also uncovered urine proteins that outperform current FDA-approved markers in many respects. Several urine proteins (d-dimer, Apolipoprotein A1, MMP-1, Properdin, Calgranulin B) significantly discriminate BC from UC with AUC values from 0.85 to 0.96 (p-value<0.0001). As a single biomarker, urine d-dimer was able to discriminate BC from UC with 96% accuracy (sensitivity=95%; specificity=90%). Likewise, several urine proteins (IL-8, IgA, Fibronectin, C2, Proteinase 3) significantly discriminate MIBC from NMIBC with AUC 0.840.99 (p-value<0.001). Interestingly, several of the proteins described above have been documented to be elevated in bladder cancer tissue (at the RNA or protein level) and/or implicated in tumor biology at some level, as summarized in Additional file 1: Table S5. Considering their biomarker potential and functional properties based on the literature (Additional file 1: Table S5), these urine proteins warrant further investigation, including, d-dimer [34], Apolipoprotein A1 [35, 36], Apolipoprotein L1, Calgranulin B [37, 38], complement C2 [39], Fibronectin [40,41,42,43], Ficolin-3, IL-8 [44,45,46,47,48,49], IgA [50], MMP-1 [51, 52], Properdin, and Proteinase 3 [53]. A summary of previous research on these proteins can be found in Additional file 1: Table S6. Additional markers increased in tissues are described in Additional file 1: Table S7.d-dimer is a specific cleavage product of fibrin and a symbol of hyperfibrinolysis [34]. It is the primary diagnostic tool in various diseases, such as deep venous thrombosis, systemic illness, and cancers [54]. Previous studies have reported that molecules in the coagulation/fibrinolysis system, especially plasma fibrinogen and d-dimer, are abnormal in cancer patients [34]. In the present study, urine d-dimer levels show a significant ability to differentiate BC from UC (AUC=0.96) (p<0.0001). After correcting for patient demographics, urine d-dimer is still eligible for inclusion within the 5-biomarker panel for best distinguishing BC from UC. Perhaps most impressive is the observation that urine d-dimer demonstrates a high sensitivity for the detection of BC (95%), and at a fixed specificity of 0.8, it can achieve a sensitivity of 0.97. Hence, as a single biomarker, urine d-dimer outperforms current FDA-approved biomarkers and competing biomarkers in the research literature as a sensitive biomarker for BC detection.

Apolipoproteins (Apolipoprotein A1 and Apolipoprotein L1) are proteins known to interact with the lipids of the lipoprotein core and also the aqueous environment of the plasma. Apolipoprotein A1 is the primary protein component of high-density lipoprotein while Apolipoprotein L1 is a minor component. Previous studies have validated Apolipoprotein A1 as a novel urinary biomarker for BC [35, 36]. In the current research, Apolipoprotein A1 was the second-best performing protein in terms of the AUC value (0.91) in distinguishing BC from UC.

After adjusting for demographics, this protein ranked within a 5-marker panel for distinguishing BC from UC. Similarly, Apolipoprotein L1 also ranked within the 5-marker panel for distinguishing BC from UC and MIBC from NMIBC.

Calgranulin B (S100A9) is a zinc- and calcium-binding protein that plays a prominent role in regulating inflammatory and immune responses. Several S100 proteins, including S100A9, have received attention regarding their possible role in tumor development and progression and studies report an increased expression in a variety of tumors, including ovarian, colon, gastric, and prostate cancer [37]. Increased expression of S100A9 protein in the serum has been previously associated with tumor grade [37]. Current validation results of Calgranulin B are promising as it was among the top markers in discriminating BC from UC with an AUC of 0.85.

Complement proteins may promote tumor growth in the context of chronic inflammation [39]. Complement C2s relation to BC at this time is unknown. However, the present study identified this protein as the fourth best single protein for differentiating MIBC from the NMIBC stage. Properdin is also a member of the complement system, controlling the alternate pathway of complement activation. Research on properdin in BC is limited. However, in the current study, properdin demonstrated the third highest AUC value (AUC=0.89, p<0.0001) in discriminating BC from UC. These biomarker findings are consistent with the observation that changes in complement activation constitute one of the major pathways that predict BC disease progression, based on STEM analysis (Fig.3D).

Fibronectin is a glycoprotein component of the extracellular matrix. Tumor cells can attach to fibronectin via integrins or other cell surface receptors [55]. Its effectiveness as a urine biomarker for BC has been explored in a variety of studies [40,41,42,43]. Here, fibronectin showed the third best discriminatory ability in identifying MIBC compared to NMIBC. The marker exhibited an AUC value of 0.87 (p<0.0001).

IL-8 is a proinflammatory CXC chemokine. It has previously been associated with the promotion of neutrophil chemotaxis and degranulation [56]. Increased expression of IL-8 has been associated with endothelial cells, infiltrating neutrophils, tumor-associated macrophages, and cancer cells [56]. Therefore, IL-8 may be a significant regulatory factor within the tumor microenvironment. Previous studies have identified urinary IL-8 as a potential marker for BC [44,45,46,47,48,49]. In the present study, urine IL-8 was the best-performing protein in the MIBC vs NMIBC comparison, with an AUC of 0.99 (p<0.0001), although its specificity was modest at a fixed sensitivity of 80%. Taken together with a wealth of supporting literature, this marker has the potential to be a monitoring tool for BC disease progression and warrants further analysis in this context.

IgA is an immunoglobulin and is often the first line of defense in the resistance against infections, particularly in mucosal tissues. A correlation of intra-tumor IgA1 and poor overall survival in BC patients has been identified in a previous study [50]. However, research regarding IgA in BC urine is limited. The data presented in this study indicated that urinary IgA may differentiate MIBC from NMIBC (AUC=0.89, p<0.0001). Overall, IgA performed 2nd best out of a total of 30 urinary markers validated for this comparison. Of particular note, urine IgA exhibited the highest specificity of 80% for MIBC, at 80% sensitivity, out-performing IL-8.

Matrix metalloproteinases (MMP) are a group of zinc-dependent proteolytic enzymes. Their role involves remodeling of the extracellular matrix. Many studies have evaluated the levels of MMPs in cancer patients and have reported the vital roles of some MMPs as potential diagnostic and prognostic biomarkers in tumorigenesis [57]. The current study has uncovered MMP-1 as the fourth best-performing molecule for distinguishing BC from UC (AUC=0.89, p<0.0001). This protein was also included in a 5-marker panel for distinguishing BC from UC. At the mechanistic level, one can envision tissue matrix remodeling as an important pre-requisite for cancer progression.

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Comprehensive proteomics and platform validation of urinary ... - BMC Medicine