Persistent exposure to low-dose of cadmium is strongly linked to both the development and prognosis of non-small cell lung cancer (NSCLC), yet the precise molecular mechanism behind this relationship Show more
Persistent exposure to low-dose of cadmium is strongly linked to both the development and prognosis of non-small cell lung cancer (NSCLC), yet the precise molecular mechanism behind this relationship remains uncertain. In this study, cadmium-related pathogenic genes (CRPGs) in NSCLC were identified via differential expression analysis. NSCLC patient clusters related to CRPGs were constructed through univariate Cox and K-means clustering algorithms. Multivariate Cox and least absolute shrinkage and selection operator (LASSO) regression analyses were employed to determine the prognosis. Sixteen CRPGs showed a significant association with NSCLC. We found biological and prognostic differences between patients in clusters A and B. A predictive prognostic risk model for NSCLC revealed that FAM83H, MSMO1, and SNAI1 are central. Hence, the 3 hub genes were named. To further elucidate the role of CRPGs in NSCLC, A549 cells were exposed to CdCl Show less
To identify the molecular basis of inherited retinal degeneration (IRD) in a familial case of Pakistani origin using whole-exome sequencing. A thorough ophthalmic examination was completed, and genomi Show more
To identify the molecular basis of inherited retinal degeneration (IRD) in a familial case of Pakistani origin using whole-exome sequencing. A thorough ophthalmic examination was completed, and genomic DNA was extracted using standard protocols. Whole exome(s) were captured with Agilent V5 + UTRs probes and sequenced on Illumina HiSeq genome analyzer. The exomeSuite software was used to filter variants, and the candidate causal variants were prioritized, examining their allele frequency and PolyPhen2, SIFT, and MutationTaster predictions. Sanger dideoxy sequencing was performed to confirm the segregation with disease phenotype and absence in ethnicity-matched control chromosomes. Ophthalmic examination confirmed retinal degeneration in all affected individuals that segregated as an autosomal recessive trait in the family. Whole-exome sequencing identified two homozygous missense variants: c.1304G > A; p.Arg435Gln in ZNF408 (NM₀₂₄₇₄₁₎ and c.902G > A; p.Gly301Asp in C1QTNF4 (NM₀₃₁₉₀₉₎. Both variants segregated with the retinal phenotype in the PKRD320 and were absent in ethnically matched control chromosomes. Whole-exome sequencing coupled with bioinformatics analysis identified potential novel variants that might be responsible for IRD. Show less