Background: Chemotherapy is the mainstay to treat metastatic colorectal cancer (CRC). However, a sizeable proportion of patients do not respond to treatment, which leads to the recurrence of disease. This study was carried out to identify reliable gene expression-based marker(s) to predict the response to chemotherapy and the risk of recurrence. Methods: This prospective study involved the collection of tumor tissues (n = 100) and normal tissues (n = 10) from CRC patients who primarily underwent surgical treatment. Global gene expression profiles were generated on microarray (Affymetrix; n = 5) and the next-generation sequencing (NGS) (Illumina; n = 20) platforms. Patients were classified as responders (n = 13; complete response with no relapse) or non-responders (n = 12; recurrence of disease leading to death). Common dysregulated genes identified from both platforms were replicated in an independent set (n = 75; quantitative real-time polymerase chain reaction (qRT-PCR)). The area under the curve (AUC) was generated, and a combinatorial analysis was performed. Results: A total of 193 and 1351 genes were dysregulated in microarray and NGS datasets, respectively. Of the top common genes (PTGIS, LYVE1, C3, C7, CXCL12, CEACAM6, MUC13, and ST14) that were selected for replication, upregulation of five genes (PTGIS, C3, C7, LYVE1, and CXCL12) were associated with the non-responder group in validation set. Combinatorial analysis and comparison of AUC identified a significant increase (p = 0.03) in AUC by 15.2% (95% confidence interval (CI): 0.01-0.29) for two genes (PTGIS and LYVE1). Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were 88.9%, 100%, 100%, and 95.6%, respectively. Conclusion: Assessing upregulation of the PTGIS and LYVE1 genes enables identification of individuals who may not respond to adjuvant chemotherapy and the risk of recurrence. The addition of drugs targeting these genes may improve response and benefit the patients.
Coronavirus disease (COVID-19) continues to be a major health concern leading to substantial mortality and morbidity across the world. Vaccination is effective in reducing the severity and associated mortality. Data pertaining to the duration of immunity, antibody waning and the optimal timing of booster dose administration is limited. In this cross-sectional study, we assessed the antibody levels in healthcare workers who were fully vaccinated after obtaining Institutional ethics committee approval and informed consent. Whole blood was collected and enumeration of S1/S2 neutralizing antibody levels was carried out using LIAISON SARS-COV-2 S1/S2 IgG assay. A total of 1636 individuals who were vaccinated with Covaxin or Covishield were included. Of these, 52% were males with a median age of 29 years. Diabetes and Hypertension was noted in 2.32% (38/1636) and 2.87% (47/1636) of the individuals. Spike neutralizing antibodies were below the detectable range (<15 AU/ml) in 6.0% (98/1636) of the individuals. Decline in neutralizing antibody was seen in 30% of the individuals above 40 years of age with comorbidities (diabetes and hypertension) after 6 months. These individuals may be prioritized for a booster dose at 6 months.
Background: A splice variant (rs72613567:TA) in 17-beta-hydroxysteroid dehydrogenase 13 gene (HSD17B13) resulting in truncated protein was reported to confer protection against NAFLD. Furthermore, it was associated with reduced levels of liver enzymes (ALT/AST) and mitigated the risk associated with PNPLA3-I148M. This gene is being explored as a therapeutic target apart from including the variant in Polygenic risk scores to predict the risk of NAFLD. Aims: This study was envisaged to explore the association of the variant with NAFLD in the Indian ethnicity. Methods: This is a retrospective study that recruited individuals (n=583) with and without fat detected on the ultrasound and biopsy proven NASH. Demographic data and blood samples were collected. Variants in HSD17B13 and PNPLA3 were genotyped (Taqman probes/qRT-PCR). Additionally, intron-exon boundaries of the HSD17B13 gene were sequenced to identify other splice variants. Variant based protein expression was estimated (Immunohistochemistry). Student's t test, Chi- square test and odds ratio (95% CI) were done to interpret the differences between the groups. Results: Significant differences were noted in anthropometric and clinical data between the groups. No significant difference (P=0.39) was noted in the frequency of the rs72613567-A-INS between controls and patients (15.0%Vs16.4%). There was no significant difference in the ALT (64.8±4.02Vs63.1±4.7;P=0.8) and AST levels (45.9±1.8Vs51.4±3.3;P=0.12) between HSD17B13-wild and variant carriers. In addition, no difference in the liver enzymes was seen between PNPLA3-I148M/HSD17B13-wild and PNPLA3-I148M/HSD17B13-variant (93.4±5.9Vs 112.6±9.8;P=0.08). No other variants in the intron-exon boundaries were identified. Genotype based differences in expression was noted with higher expression in the wild type and relatively lower expression in the mutants. Conclusion: Although, there was a genotype based difference in the protein expression of HSD17B13, there was no association of splice variant in HSD17B13 gene with protection against NAFLD in the Indian ethnicity. The absence of protection in variant carriers is intriguing and needs to be explored.
