Loss of heterozygosity related to TMB and TNB may predict PFS for patients with SCLC received the first line setting

Zhang, Chenyue; Wang, Kai

doi:10.1186/s12967-021-03019-6

Cited by 3 publications

(3 citation statements)

References 6 publications

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“…Besides such an approach can identify the concomitant presence of LOH and HR mutations in certain cases, which could be a more valuable predictive marker of PARPi sensitivity compared to the analysis of each of these events individually (10) Furthermore, in our cohort, no statistically significant association was observed in our cohort between LOH and other non-HR gene mutations or high TMB values. This is in agreement with other studies (27).…”

Section: Discussionsupporting

confidence: 94%

The Utility of Comprehensive NGS Analysis in Homologous Recombination Deficiency Tracking

Tsantikidi¹,

Papadopoulou²,

Tsaousis³

et al. 2023

Preprint

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Several tumor types have been efficiently treated with PARPis, which are now approved for the treatment of ovarian, breast, prostate, and pancreatic cancer. The BRCA1/2 genes and mutations in many additional genes involved in the HR pathway may be responsible for the HRD phenomenon. In the present study, an NGS assay was used to analyze 513 genes associated with targeted and immuno-oncology therapies in 406 samples. In addition, the %gLOH values of 24 samples were also calculated using the Affymetrix technology to compare the results obtained by the two methodologies. HR variations occurred in 20.93% of the malignancies, while BRCA1/2 gene alterations in 5.17%. %LOH was highly correlated with alterations in the BRCA1/2 genes since 76.19% (16/21) of the BRCA1/2 positive tumors had a high %LOH value (p=0.007). Moreover, the LOH status was highly correlated with the TP53 and KRAS statuses, but there was no association with the TMB value. Lin's Concordance Correlation Coefficient for the 24 evaluable samples simultaneously examined by both assays was 0.87, indicating a nearly perfect agreement. In conclusion, the addition of gLOH analysis could assist the detection of additional patients eligible for PARPis

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Section: Discussionsupporting

confidence: 94%

The Utility of Comprehensive NGS Analysis in Homologous Recombination Deficiency Tracking

Tsantikidi¹,

Papadopoulou²,

Tsaousis³

et al. 2023

Preprint

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show abstract

“…Enhanced sensitivity to ICI could, therefore, be predicted for HRD-positive tumors, which is under investigation in a number of ongoing clinical trials. In our cohort, however, in agreement with other studies, no statistically significant association was observed between LOH and other non-HR gene mutations or high TMB values [ 32 ]. In breast and ovarian cancer tumors with a known mutation in HR genes, such as BRCA1 or BRCA2 , a higher tumor mutational burden and a greater number of tumor-infiltrating lymphocytes have been observed [ 33 ]; however, this outcome did not occur in our cohort.…”

Section: Discussionsupporting

confidence: 93%

The Utility of NGS Analysis in Homologous Recombination Deficiency Tracking

Tsantikidi,

Papadopoulou,

Metaxa-Mariatou

et al. 2023

Diagnostics

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Several tumor types have been efficiently treated with PARP inhibitors (PARPis), which are now approved for the treatment of ovarian, breast, prostate, and pancreatic cancers. The BRCA1/2 genes and mutations in many additional genes involved in the HR pathway may be responsible for the HRD phenomenon. The aim of the present study was to investigate the association between genomic loss of heterozygosity (gLOH) and alterations in 513 genes with targeted and immuno-oncology therapies in 406 samples using an NGS assay. In addition, the %gLOHs of 24 samples were calculated using the Affymetrix technology in order to compare the results obtained via the two methodologies. HR variations occurred in 20.93% of the malignancies, while BRCA1/2 gene alterations occurred in 5.17% of the malignancies. The %LOH was highly correlated with alterations in the BRCA1/2 genes, since 76.19% (16/21) of the BRCA1/2 positive tumors had a high %LOH value (p = 0.007). Moreover, the LOH status was highly correlated with the TP53 and KRAS statuses, but there was no association with the TMB value. Lin’s concordance correlation coefficient for the 24 samples simultaneously examined via both assays was 0.87, indicating a nearly perfect agreement. In conclusion, the addition of gLOH analysis could assist in the detection of additional patients eligible for treatment with PARPis.

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“…HRD leads to genomic instability and is indicative of the response to chemotherapy and polyadenosine diphosphate ribose polymerase (PARP) inhibition, particularly with platinum-based therapies [ 46 , 47 ]. LOH, characterized by the loss of one allele, is an irreversible genetic alteration often associated with the loss of tumor suppressor gene function and plays a pivotal role in tumor development [ 48 , 49 ]. Figure 11 A shows that WDHD1 expression was significantly and positively correlated with TMB scores in 14 types of cancer.…”

Section: Resultsmentioning

confidence: 99%

Integrative bioinformatics analysis of WDHD1: a potential biomarker for pan-cancer prognosis, diagnosis, and immunotherapy

Cui,

Zou,

Wang

et al. 2023

World J Surg Onc

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Background Although WD repeat and high-mobility group box DNA binding protein 1 (WDHD1) played an essential role in DNA replication, chromosome stability, and DNA damage repair, the panoramic picture of WDHD1 in human tumors remains unclear. Hence, this study aims to comprehensively characterize WDHD1 across 33 human cancers. Methods Based on publicly available databases such as TCGA, GTEx, and HPA, we used a bioinformatics approach to systematically explore the genomic features and biological functions of WDHD1 in pan-cancer. Results WDHD1 mRNA levels were significantly increased in more than 20 types of tumor tissues. Elevated WDHD1 expression was associated with significantly shorter overall survival (OS) in 10 tumors. Furthermore, in uterine corpus endometrial carcinoma (UCEC) and liver hepatocellular carcinoma (LIHC), WDHD1 expression was significantly associated with higher histological grades and pathological stages. In addition, WDHD1 had a high diagnostic value among 16 tumors (area under the ROC curve [AUC] > 0.9). Functional enrichment analyses suggested that WDHD1 probably participated in many oncogenic pathways such as E2F and MYC targets (false discovery rate [FDR] < 0.05), and it was involved in the processes of DNA replication and DNA damage repair (p.adjust < 0.05). WDHD1 expression also correlated with the half-maximal inhibitory concentrations (IC50) of rapamycin (4 out of 10 cancers) and paclitaxel (10 out of 10 cancers). Overall, WDHD1 was negatively associated with immune cell infiltration and might promote tumor immune escape. Our analysis of genomic alterations suggested that WDHD1 was altered in 1.5% of pan-cancer cohorts and the “mutation” was the predominant type of alteration. Finally, through correlation analysis, we found that WDHD1 might be closely associated with tumor heterogeneity, tumor stemness, mismatch repair (MMR), and RNA methylation modification, which were all processes associated with the tumor progression. Conclusions Our pan-cancer analysis of WDHD1 provides valuable insights into the genomic characterization and biological functions of WDHD1 in human cancers and offers some theoretical support for the future use of WDHD1-targeted therapies, immunotherapies, and chemotherapeutic combinations for the management of tumors.

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Loss of heterozygosity related to TMB and TNB may predict PFS for patients with SCLC received the first line setting

Cited by 3 publications

References 6 publications

The Utility of Comprehensive NGS Analysis in Homologous Recombination Deficiency Tracking

The Utility of Comprehensive NGS Analysis in Homologous Recombination Deficiency Tracking

The Utility of NGS Analysis in Homologous Recombination Deficiency Tracking

Integrative bioinformatics analysis of WDHD1: a potential biomarker for pan-cancer prognosis, diagnosis, and immunotherapy

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