Exploring SARS-CoV-2 infection and vaccine-induced immunity in chronic myeloid leukemia patients: insights from real-world data in Brazil and the United States.

This study investigates COVID-19 outcomes and immune response in chronic myeloid leukemia (CML) patients post-SARS-CoV-2 vaccination, comparing effectiveness of various vaccine options. Data from 118 CML patients (85 in Brazil, 33 in the US) showed similar infection rates prior (14% Brazil, 9.1% US) and post-vaccination (24.7% vs. 27.3%, respectively). In Brazil, AstraZeneca and CoronaVac were the most commonly used vaccine brands, while in the US, Moderna and Pfizer-BioNTech vaccines dominated. Despite lower seroconversion in the Brazilian cohort, all five vaccine brands analyzed prevented severe COVID-19. Patients who received mRNA and recombinant viral vector vaccines (HR: 2.20; 95%CI 1.07-4.51; p < .031) and those that had achieved at least major molecular response (HR: 1.51; 95% CI 1.01-3.31; p < .0001) showed higher seroconversion rates. Our findings suggest that CML patients can generate antibody responses regardless of the vaccine brand, thereby mitigating severe COVID-19. This effect is more pronounced in patients with well-controlled disease.

Gene Regulatory Network Analysis of Post-Mortem Lungs Unveils Novel Insights into COVID-19 Pathogenesis.

The novel coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has emerged as one of the most significant global health crises in recent history. The clinical characteristics of COVID-19 patients have revealed the possibility of immune activity changes contributing to disease severity. Nevertheless, limited information is available regarding the immune response in human lung tissue, which is the primary site of infection. In this study, we conducted an extensive analysis of lung tissue to screen for differentially expressed miRNAs and mRNAs in five individuals who died due to COVID-19 and underwent a rapid autopsy, as well as seven control individuals who died of other causes unrelated to COVID-19. To analyze the host response gene expression, miRNA microarray and Nanostring's nCounter XT gene expression assay were performed. Our study identified 37 downregulated and 77 upregulated miRNAs in COVID-19 lung biopsy samples compared to the controls. A total of 653 mRNA transcripts were differentially expressed between the two sample types, with most transcripts (472) being downregulated in COVID-19-positive specimens. Hierarchical and PCA K-means clustering analysis showed distinct clustering between COVID-19 and control samples. Enrichment and network analyses revealed differentially expressed genes important for innate immunity and inflammatory response in COVID-19 lung biopsies. The interferon-signaling pathway was highly upregulated in COVID-19 specimens while genes involved in interleukin-17 signaling were downregulated. These findings shed light on the mechanisms of host cellular responses to COVID-19 infection in lung tissues and could help identify new targets for the prevention and treatment of COVID-19 infection.

Single episode of moderate to severe traumatic brain injury leads to chronic neurological deficits and Alzheimer's-like pathological dementia.

Traumatic brain injury (TBI) is one of the foremost causes of disability and mortality globally. While the scientific and medical emphasis is to save lives and avoid disability during acute period of injury, a severe health problem can manifest years after injury. For instance, TBI increases the risk of cognitive impairment in the elderly. Remote TBI history was reported to be a cause of the accelerated clinical trajectory of Alzheimer's disease-related dementia (ADRD) resulting in earlier onset of cognitive impairment and increased AD-associated pathological markers like greater amyloid deposition and cortical thinning. It is not well understood whether a single TBI event may increase the risk of dementia. Moreover, the cellular signaling pathways remain elusive for the chronic effects of TBI on cognition. We have hypothesized that a single TBI induces sustained neuroinflammation and disrupts cellular communication in a way that results later in ADRD pathology. To test this, we induced TBI in young adult CD1 mice and assessed the behavioral outcomes after 11 months followed by pathological, histological, transcriptomic, and MRI assessment. On MRI scans, these mice showed significant loss of tissue, reduced CBF, and higher white matter injury compared to sham mice. We found these brains showed progressive atrophy, markers of ADRD, sustained astrogliosis, loss of neuronal plasticity, and growth factors even after 1-year post-TBI. Because of progressive neurodegeneration, these mice had motor deficits, showed cognitive impairments, and wandered randomly in open field. We, therefore, conclude that progressive pathology after adulthood TBI leads to neurodegenerative conditions such as ADRD and impairs neuronal functions.

Comprehensive Analysis of Clinically Relevant Copy Number Alterations (CNAs) Using a 523-Gene Next-Generation Sequencing Panel and NxClinical Software in Solid Tumors.

Copy number alterations (CNAs) are significant in tumor initiation and progression. Identifying these aberrations is crucial for targeted therapies and personalized cancer diagnostics. Next-generation sequencing (NGS) methods present advantages in scalability and cost-effectiveness, surpassing limitations associated with reference assemblies and probe capacities in traditional laboratory approaches. This retrospective study evaluated CNAs in 50 FFPE tumor samples (breast cancer, ovarian carcinoma, pancreatic cancer, melanoma, and prostate carcinoma) using Illumina's TruSight Oncology 500 (TSO500) and the Affymetrix Oncoscan Molecular Inversion Probe (OS-MIP) (ThermoFisher Scientific, Waltham, MA, USA). NGS analysis with the NxClinical 6.2 software demonstrated a high sensitivity and specificity (100%) for CNA detection, with a complete concordance rate as compared to the OS-MIP. All 54 known CNAs were identified by NGS, with gains being the most prevalent (63%). Notable CNAs were observed in MYC (18%), TP53 (12%), BRAF (8%), PIK3CA, EGFR, and FGFR1 (6%) genes. The diagnostic parameters exhibited high accuracy, including a positive predictive value, negative predictive value, and overall diagnostic accuracy. This study underscores NxClinical as a reliable software for identifying clinically relevant gene alterations using NGS TSO500, offering valuable insights for personalized cancer treatment strategies based on CNA analysis.

Incorporating Novel Technologies in Precision Oncology for Colorectal Cancer: Advancing Personalized Medicine.

Colorectal cancer (CRC) is one of the most heterogeneous and deadly diseases, with a global incidence of 1.5 million cases per year. Genomics has revolutionized the clinical management of CRC by enabling comprehensive molecular profiling of cancer. However, a deeper understanding of the molecular factors is needed to identify new prognostic and predictive markers that can assist in designing more effective therapeutic regimens for the improved management of CRC. Recent breakthroughs in single-cell analysis have identified new cell subtypes that play a critical role in tumor progression and could serve as potential therapeutic targets. Spatial analysis of the transcriptome and proteome holds the key to unlocking pathogenic cellular interactions, while liquid biopsy profiling of molecular variables from serum holds great potential for monitoring therapy resistance. Furthermore, gene expression signatures from various pathways have emerged as promising prognostic indicators in colorectal cancer and have the potential to enhance the development of equitable medicine. The advancement of these technologies for identifying new markers, particularly in the domain of predictive and personalized medicine, has the potential to improve the management of patients with CRC. Further investigations utilizing similar methods could uncover molecular subtypes specific to emerging therapies, potentially strengthening the development of personalized medicine for CRC patients.

Optical Genome Mapping for Oncology Applications.

Optical genome mapping (OGM) is a next-generation cytogenomic technology that has the potential to replace standard-of-care technologies used in the genetic workup of various malignancies. The ability to detect various classes of structural variations that include copy number variations, deletions, duplications, balanced and unbalanced events (insertions, inversions, and translocation) and complex genomic rearrangements in a single assay and analysis demonstrates the utility of the technology in tumor research and clinical application. Herein, we provide the methodological details for performing OGM and pre- and post-analytical quality control (QC) checks and describe critical steps that should be performed with caution, probable causes for specific QC failures, and potential method modifications that could be implemented as part of troubleshooting. The protocol description and troubleshooting guide should help new and current users of the technology to improve or troubleshoot the problems (if any) in their workflow. © 2023 Wiley Periodicals LLC. Basic Protocol: Optical genome mapping.

Ethno-demographic disparities in humoral responses to the COVID-19 vaccine among healthcare workers.

The COVID-19 pandemic had a profound impact on global health, but rapid vaccine administration resulted in a significant decline in morbidity and mortality rates worldwide. In this study, we sought to explore the temporal changes in the humoral immune response against SARS-CoV-2 healthcare workers (HCWs) in Augusta, GA, USA, and investigate any potential associations with ethno-demographic features. Specifically, we aimed to compare the naturally infected individuals with naïve individuals to understand the immune response dynamics after SARS-CoV-2 vaccination. A total of 290 HCWs were included and assessed prospectively in this study. COVID status was determined using a saliva-based COVID assay. Neutralizing antibody (NAb) levels were quantified using a chemiluminescent immunoassay system, and IgG levels were measured using an enzyme-linked immunosorbent assay method. We examined the changes in antibody levels among participants using different statistical tests including logistic regression and multiple correspondence analysis. Our findings revealed a significant decline in NAb and IgG levels at 8-12 months postvaccination. Furthermore, a multivariable analysis indicated that this decline was more pronounced in White HCWs (odds ratio [OR] = 2.1, 95% confidence interval [CI] = 1.07-4.08, p = 0.02) and IgG (OR = 2.07, 95% CI = 1.04-4.11, p = 0.03) among the whole cohort. Booster doses significantly increased IgG and NAb levels, while a decline in antibody levels was observed in participants without booster doses at 12 months postvaccination. Our results highlight the importance of understanding the dynamics of immune response and the potential influence of demographic factors on waning immunity to SARS-CoV-2. In addition, our findings emphasize the value of booster doses to ensure durable immunity.

Optical Genome Mapping: Integrating Structural Variations for Precise Homologous Recombination Deficiency Score Calculation.

Homologous recombination deficiency (HRD) is characterized by the inability of a cell to repair the double-stranded breaks using the homologous recombination repair (HRR) pathway. The deficiency of the HRR pathway results in defective DNA repair, leading to genomic instability and tumorigenesis. The presence of HRD has been found to make tumors sensitive to ICL-inducing platinum-based therapies and poly(adenosine diphosphate [ADP]-ribose) polymerase (PARP) inhibitors (PARPi). However, there are no standardized methods to measure and report HRD phenotypes. Herein, we compare optical genome mapping (OGM), chromosomal microarray (CMA), and a 523-gene NGS panel for HRD score calculations. This retrospective study included the analysis of 196 samples, of which 10 were gliomas, 176 were hematological malignancy samples, and 10 were controls. The 10 gliomas were evaluated with both CMA and OGM, and 30 hematological malignancy samples were evaluated with both the NGS panel and OGM. To verify the scores in a larger cohort, 135 cases were evaluated with the NGS panel and 71 cases with OGM. The HRD scores were calculated using a combination of three HRD signatures that included loss of heterozygosity (LOH), telomeric allelic imbalance (TAI), and large-scale transitions (LST). In the ten glioma cases analyzed with OGM and CMA using the same DNA (to remove any tumor percentage bias), the HRD scores (mean ± SEM) were 13.2 (±4.2) with OGM compared to 3.7 (±1.4) with CMA. In the 30 hematological malignancy cases analyzed with OGM and the 523-gene NGS panel, the HRD scores were 7.6 (±2.2) with OGM compared to 2.6 (±0.8) with the 523-gene NGS panel. OGM detected 70.8% and 66.8% of additional variants that are considered HRD signatures in gliomas and hematological malignancies, respectively. The higher sensitivity of OGM to capture HRD signature variants might enable a more accurate and precise correlation with response to PARPi and platinum-based drugs. This study reveals HRD signatures that are cryptic to current standard of care (SOC) methods used for assessing the HRD phenotype and presents OGM as an attractive alternative with higher resolution and sensitivity to accurately assess the HRD phenotype.

Clinical Utility of Optical Genome Mapping and 523-Gene Next Generation Sequencing Panel for Comprehensive Evaluation of Myeloid Cancers.

The standard-of-care (SOC) for genomic testing of myeloid cancers primarily relies on karyotyping/fluorescent in situ hybridization (FISH) (cytogenetic analysis) and targeted gene panels (usually ≤54 genes) that harbor hotspot pathogenic variants (molecular genetic analysis). Despite this combinatorial approach, ~50% of myeloid cancer genomes remain cytogenetically normal, and the limited sequencing variant profiles obtained from targeted panels are unable to resolve the molecular etiology of many myeloid tumors. In this study, we evaluated the performance and clinical utility of combinatorial use of optical genome mapping (OGM) and a 523-gene next-generation sequencing (NGS) panel for comprehensive genomic profiling of 30 myeloid tumors and compared it to SOC cytogenetic methods (karyotyping and FISH) and a 54-gene NGS panel. OGM and the 523-gene NGS panel had an analytical concordance of 100% with karyotyping, FISH, and the 54-gene panel, respectively. Importantly, the IPSS-R cytogenetic risk group changed from very good/good to very poor in 22% of MDS (2/9) cases based on comprehensive profiling (karyotyping, FISH, and 54-gene panel vs. OGM and 523-gene panel), while additionally identifying six compound heterozygous events of potential clinical relevance in six cases (6/30, 20%). This cost-effective approach of using OGM and a 523-gene NGS panel for comprehensive genomic profiling of myeloid cancers demonstrated increased yield of actionable targets that can potentially result in improved clinical outcomes.

Reduction of SARS-CoV-2 salivary viral load with pre-procedural mouth rinses: a randomised, controlled, clinical trial.

Introduction The purpose of this study was to test the short-term efficacy of four commercial mouthwashes versus water in reducing SARS-CoV-2 viral load in the oral cavity over clinically relevant time points.Methods In total, 32 subjects that were proven SARS-CoV-2-positive via polymerase chain reaction (PCR)-based diagnostic test were recruited and randomised into five parallel arms. Cycle threshold (Ct) values were compared in saliva samples between the groups, as well as within the groups at baseline (pre-rinse), zero hours, one hour and two hours post-rinse, using SARS-CoV-2 reverse transcription-PCR analysis.Results We observed a significant increase in Ct values in saliva samples collected immediately after rinsing with all the four mouthwashes - 0.12% chlorhexidine gluconate, 1.5% hydrogen peroxide, 1% povidone iodine, or Listerine - compared to water. A sustained increase in Ct values for up to two hours was only observed in the Listerine and chlorohexidine gluconate groups. We were not able to sufficiently power this clinical trial, so the results remain notional but encouraging and supportive of findings in other emerging mouthwash studies on COVID-19, warranting additional investigations.Conclusions Our evidence suggests that in a clinical setting, prophylactic rinses with Listerine or chlorhexidine gluconate can potentially reduce SARS-CoV-2 viral load in the oral cavity for up to two hours. While limited in statistical power due to the difficulty in obtaining this data, we advocate for pre-procedural mouthwashing, like handwashing, as an economical and safe additional precaution to help mitigate the transmission of SARS-CoV-2 from a potentially infected patient to providers.

Immune Factors Drive Expression of SARS-CoV-2 Receptor Genes Amid Sexual Disparity.

The emergence of COVID-19 has led to significant morbidity and mortality, with around seven million deaths worldwide as of February 2023. There are several risk factors such as age and sex that are associated with the development of severe symptoms due to COVID-19. There have been limited studies that have explored the role of sex differences in SARS-CoV-2 infection. As a result, there is an urgent need to identify molecular features associated with sex and COVID-19 pathogenesis to develop more effective interventions to combat the ongoing pandemic. To address this gap, we explored sex-specific molecular factors in both mouse and human datasets. The host immune targets such as TLR7, IRF7, IRF5, and IL6, which are involved in the immune response against viral infections, and the sex-specific targets such as AR and ESSR were taken to investigate any possible link with the SARS-CoV-2 host receptors ACE2 and TMPRSS2. For the mouse analysis, a single-cell RNA sequencing dataset was used, while bulk RNA-Seq datasets were used to analyze the human clinical data. Additional databases such as the Database of Transcription Start Sites (DBTS), STRING-DB, and the Swiss Regulon Portal were used for further analysis. We identified a 6-gene signature that showed differential expression in males and females. Additionally, this gene signature showed potential prognostic utility by differentiating ICU patients from non-ICU patients due to COVID-19. Our study highlights the importance of assessing sex differences in SARS-CoV-2 infection, which can assist in the optimal treatment and better vaccination strategies.

Clinical Validation and Diagnostic Utility of Optical Genome Mapping in Prenatal Diagnostic Testing.

The standard-of-care diagnostic prenatal testing includes a combination of cytogenetic methods, such as karyotyping, fluorescence in situ hybridization (FISH), and chromosomal microarray (CMA), using either direct or cultured amniocytes or chorionic villi sampling. However, each technology has its limitations: karyotyping has a low resolution (>5 Mb), FISH is targeted, and CMA does not detect balanced structural variations (SVs). These limitations necessitate the use of multiple tests, either simultaneously or sequentially, to reach a genetic diagnosis. Optical genome mapping (OGM) is an emerging technology that can detect several classes of SVs in a single assay, but it has not been evaluated in the prenatal setting. This validation study analyzed 114 samples that were received in our laboratory for traditional cytogenetic analysis with karyotyping, FISH, and/or CMA. OGM was 100% concordant in identifying the 101 aberrations that included 29 interstitial/terminal deletions, 28 duplications, 26 aneuploidies, 6 absence of heterozygosity regions, 3 triploid genomes, 4 isochromosomes, and 1 translocation; and the method revealed the identity of 3 marker chromosomes and 1 chromosome with additional material not determined by karyotyping. In addition, OGM detected 64 additional clinically reportable SVs in 43 samples. OGM has a standardized laboratory workflow and reporting solution that can be adopted in routine clinical laboratories and demonstrates the potential to replace the current standard-of-care methods for prenatal diagnostic testing.

Genetic Predisposition to Neurological Complications in Patients with COVID-19.

Several studies have identified rare and common genetic variants associated with severe COVID-19, but no study has reported genetic determinants as predisposition factors for neurological complications. In this report, we identified rare/unique structural variants (SVs) implicated in neurological functions in two individuals with neurological manifestations of COVID-19. This report highlights the possible genetic link to the neurological symptoms with COVID-19 and calls for a collective effort to study these cohorts for a possible genetic linkage.

Clinical Validation and Diagnostic Utility of Optical Genome Mapping for Enhanced Cytogenomic Analysis of Hematological Neoplasms.

The current standard-of-care cytogenetic techniques for the analysis of hematological malignancies include karyotyping, fluorescence in situ hybridization, and chromosomal microarray, which are labor intensive and time and cost prohibitive, and they often do not reveal the genetic complexity of the tumor, demonstrating the need for alternative technology for better characterization of these tumors. Herein, we report the results from our clinical validation study and demonstrate the utility of optical genome mapping (OGM), evaluated using 92 sample runs (including replicates) that included 69 well-characterized unique samples (59 hematological neoplasms and 10 controls). The technical performance (quality control metrics) resulted in 100% first-pass rate, with analytical performance (concordance) showing a sensitivity of 98.7%, a specificity of 100%, and an accuracy of 99.2%. OGM demonstrated robust technical, analytical performance, and interrun, intrarun, and interinstrument reproducibility. The limit of detection was determined to be at 5% allele fraction for aneuploidy, translocation, interstitial deletion, and duplication. OGM identified several additional structural variations, revealing the genomic architecture in these neoplasms that provides an opportunity for better tumor classification, prognostication, risk stratification, and therapy selection. Overall, OGM has outperformed the standard-of-care tests in this study and demonstrated its potential as a first-tier cytogenomic test for hematologic malignancies.

Optical Genome Mapping and Single Nucleotide Polymorphism Microarray: An Integrated Approach for Investigating Products of Conception.

Conventional cytogenetic analysis of products of conception (POC) is of limited utility because of failed cultures, as well as microbial and maternal cell contamination (MCC). Optical genome mapping (OGM) is an emerging technology that has the potential to replace conventional cytogenetic methods. The use of OGM precludes the requirement for culturing (and related microbial contamination). However, a high percentage of MCC impedes a definitive diagnosis, which can be addressed by an additional pre-analytical quality control step that includes histological assessment of H&E stained slides from formalin-fixed paraffin embedded (FFPE) tissue with macro-dissection for chorionic villi to enrich fetal tissue component for single nucleotide polymorphism microarray (SNPM) analysis. To improve the diagnostic yield, an integrated workflow was devised that included MCC characterization of POC tissue, followed by OGM for MCC-negative cases or SNPM with histological assessment for MCC-positive cases. A result was obtained in 93% (29/31) of cases with a diagnostic yield of 45.1% (14/31) with the proposed workflow, compared to 9.6% (3/31) and 6.4% (2/31) with routine workflow, respectively. The integrated workflow with these technologies demonstrates the clinical utility and higher diagnostic yield in evaluating POC specimens.

Clinical validation of a multiplex PCR-based detection assay using saliva or nasopharyngeal samples for SARS-Cov-2, influenza A and B.

The COVID-19 pandemic has resulted in significant diversion of human and material resources to COVID-19 diagnostics, to the extent that influenza viruses and co-infection in COVID-19 patients remains undocumented and pose serious public-health consequences. We optimized and validated a highly sensitive RT-PCR based multiplex-assay for the detection of SARS-CoV-2, influenza A and B viruses in a single-test. This study evaluated clinical specimens (n = 1411), 1019 saliva and 392 nasopharyngeal swab (NPS), tested using two-assays: FDA-EUA approved SARS-CoV-2 assay that targets N and ORF1ab gene, and the PKamp-RT-PCR based assay that targets SARS-CoV-2, influenza viruses A and B. Of the 1019 saliva samples, 17.0% (174/1019) tested positive for SARS-CoV-2 using either assay. The detection rate for SARS-CoV-2 was higher with the multiplex assay compared to SARS-specific assay [91.9% (160/174) vs. 87.9% (153/174)], respectively. Of the 392 NPS samples, 10.4% (41/392) tested positive for SARS-CoV-2 using either assay. The detection rate for SARS-CoV-2 was higher with the multiplex assay compared to SARS-specific assay [97.5% (40/41) vs. 92.1% (39/41)], respectively. This study presents clinical validation of a multiplex-PCR assay for testing SARS-CoV-2, influenza A and B viruses, using NPS and saliva samples, and demonstrates the feasibility of implementing the assay without disrupting the existing laboratory workflow.

Clinical and molecular assessment of an onco-immune signature with prognostic significance in patients with colorectal cancer.

Understanding the complex tumor microenvironment is key to the development of personalized therapies for the treatment of cancer including colorectal cancer (CRC). In the past decade, significant advances in the field of immunotherapy have changed the paradigm of cancer treatment. Despite significant improvements, tumor heterogeneity and lack of appropriate classification tools for CRC have prevented accurate risk stratification and identification of a wider patient population that may potentially benefit from targeted therapies. To identify novel signatures for accurate prognostication of CRC, we quantified gene expression of 12 immune-related genes using a medium-throughput NanoString quantification platform in 93 CRC patients. Multivariate prognostic analysis identified a combined four-gene prognostic signature (TGFB1, PTK2, RORC, and SOCS1) (HR: 1.76, 95% CI: 1.05-2.95, *p < 0.02). The survival trend was captured in an independent gene expression data set: GSE17536 (177 patients; HR: 3.31, 95% CI: 1.99-5.55, *p < 0.01) and GSE14333 (226 patients; HR: 2.47, 95% CI: 1.35-4.53, *p < 0.01). Further, gene set enrichment analysis of the TCGA data set associated higher prognostic scores with epithelial-mesenchymal transition (EMT) and inflammatory pathways. Comparatively, a lower prognostic score was correlated with oxidative phosphorylation and MYC and E2F targets. Analysis of immune parameters identified infiltration of T-reg cells, CD8+ T cells, M2 macrophages, and B cells in high-risk patient groups along with upregulation of immune exhaustion genes. This molecular study has identified a novel prognostic gene signature with clinical utility in CRC. Therefore, along with prognostic features, characterization of immune cell infiltrates and immunosuppression provides actionable information that should be considered while employing personalized medicine.

Optical genome mapping identifies rare structural variations as predisposition factors associated with severe COVID-19.

Impressive global efforts have identified both rare and common gene variants associated with severe COVID-19 using sequencing technologies. However, these studies lack the sensitivity to accurately detect several classes of variants, especially large structural variants (SVs), which account for a substantial proportion of genetic diversity including clinically relevant variation. We performed optical genome mapping on 52 severely ill COVID-19 patients to identify rare/unique SVs as decisive predisposition factors associated with COVID-19. We identified 7 SVs involving genes implicated in two key host-viral interaction pathways: innate immunity and inflammatory response, and viral replication and spread in nine patients, of which SVs in STK26 and DPP4 genes are the most intriguing candidates. This study is the first to systematically assess the potential role of SVs in the pathogenesis of COVID-19 severity and highlights the need to evaluate SVs along with sequencing variants to comprehensively associate genomic information with interindividual variability in COVID-19 phenotypes.

Gene signatures with therapeutic value: emerging perspective for personalized immunotherapy in renal cancer.

Renal cancer is one of the deadliest urogenital diseases. In recent years, the advent of immunotherapy has led to significant improvement in the management of patients with renal cancer. Although cancer immunotherapy and its combinations had benefited numerous patients, several challenges need to be addressed. Apart from the high costs of treatment, the lack of predictive biomarkers and toxic side-effects have impeded its wider applicability. To address these issues, new biomarkers are required to predict responsiveness and design personalized treatment strategies. Recent advances in the field of single-cell sequencing and multi-dimensional spatial transcriptomics have identified clinically relevant subtypes of renal cancer. Furthermore, there is emerging potential for gene signatures based on immune cells, non-coding RNAs, and pathways such as metabolism and RNA modification. In this review article, we have discussed recent progress in the identification of gene signatures with predictive and prognostic potential in renal cancer.