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Tumor Discovery                                                   HRD genomic alterations in Chinese NSCLC




            A                                                B


















            C                                                D


















            Figure 5. KEGG pathway analysis. (A and B) KEGG pathway analysis for TCGA databases. (C and D) KEGG pathway analysis for our study participant’s
            RNA-seq data. (A and C) Bar plots display the number of genes involved in significantly enriched KEGG pathways for HRD-H tumors compared to HRD-L
            tumors. The bar color gradient indicates the adjusted p-value significance, from yellow (less significant) to purple (more significant). (B and D) Bubble
            plots summarizing KEGG pathway enrichment, with the y-axis listing pathways and the x-axis showing the Rich factor, a measure of pathway enrichment.
            Abbreviations: HRD-H: Homologous recombination deficiency-high; HRD-L: Homologous recombination deficiency-low; KEGG: Kyoto Encyclopedia of
            Genes and Genomes; RNA-seq: RNA sequencing; TCGA: The Cancer Genome Atlas.

              However, there are several limitations in this study. First,   our study provides valuable insights into the genomic
            the sample size was relatively small for certain subgroups,   landscape of HRD in Chinese NSCLC patients and lays
            such as HRD-H and LUSC, limiting the statistical power to   important groundwork for future investigations into
            detect additional associations. Second, this is a retrospective   targeted therapeutic approaches.
            study. Without prospective data collection, we were unable
            to systematically capture important clinical outcomes   5. Conclusion
            such  as  survival  data  and  treatment response  rates.  The   The present study provides preliminary evidence supporting
            retrospective design also precluded the assessment of the   the implementation of HRD status to subclassify NSCLC and
            HRD score as a direct predictor of treatment efficacy or   to guide precision therapy strategies. HRD may serve not only
            as a prognostic factor under specific therapeutic regimens.   as a biomarker for selecting patients likely to benefit from PARP
            Moreover, the discrepancy between our cohort’s data and
            the TCGA-LUAD data on PD-L1 mainly implies that    inhibitors but also as a potential predictor of immunotherapy
            genetic factors such as ancestry, tumor microenvironment,   efficacy. Future large-scale, prospective studies that integrate
            and immune system might affect the association between   comprehensive clinical data and evaluate combination
            HRD and immunogenicity on a population level. These   treatment regimens are warranted to further validate the
            limitations underscore the necessity for larger, prospective,   prognostic and therapeutic value of HRD in NSCLC.
            population-specific studies to fully elucidate the clinical   Acknowledgments
            utility of HRD as a biomarker in NSCLC and to validate
            our preliminary findings. Despite these constraints,   None.


            Volume 4 Issue 3 (2025)                         41                           doi: 10.36922/TD025180032
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