Comprehensive genomic and immunohistochemical profiles and outcomes of immunotherapy in patients with recurrent or advanced cervical cancer

Kim, Yoo-Na; Lee, Kyunglim; Park, Eunhyang; Park, Junsik; Lee, Yong Jae; Nam, Eun Ji; Kim, Sang Wun; Kim, Sung Hoon; Kim, Young Tae; Lee, Jung‐Yun

doi:10.3389/fonc.2023.1156973

Cited by 3 publications

(1 citation statement)

References 27 publications

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“…The clinical utility of targeted genomic panels, encompassing both germline susceptibility and known "actionable" somatic mutations (including TSO500), has been welldocumented [27][28][29][30][31][32][33]. For some cancer types, targeted panel sequencing is becoming standard practice [31].…”

Section: Discussionmentioning

confidence: 99%

Target-enhanced whole-genome sequencing (TE-WGS) shows clinical validity equivalent to commercially available targeted oncology panel

Lee,

Roh,

Park

et al. 2023

Preprint

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Cancer poses a significant global health challenge, with increasing incidence rates demanding precise genomic testing for individualized treatment strategies. Targeted-panel sequencing (TPS) has improved personalized oncology but often lacks comprehensive coverage of crucial cancer alterations. Whole-genome sequencing (WGS) addresses this gap, offering extensive genomic testing. This study demonstrates the potential medical application of WGS.MethodsThis study evaluates the power of target-enhanced WGS (TE-WGS), a clinical-grade WGS method sequencing both cancer and matched normal tissues. A cohort of forty-nine patients with various solid cancer types underwent both TE-WGS and TruSight Oncology 500 (TSO500), one of the mainstream TPS approaches currently used in the clinic.ResultsTE-WGS methods detected all the variants reported from TSO500 (100%, 498/498). A high correlation in the detection of variant allele fractions (VAF) was observed between the TE-WGS and TSO500 methodologies (r=0.977). Notably, within the pool of 498 variants commonly detected by both approaches, 223 variants (44.8%) were discerned within peripheral blood samples exclusively through the TE-WGS technique, suggesting their presence as constitutional variants inherent to the germline. Conversely, the remaining subset of 275 variants (55.2%) were not detected in peripheral blood using the TE-WGS method, signifying them as bona fide somatic variants. Further, TE-WGS provided accurate copy number profiles, fusion-genes, MSI- and homologous-recombination deficiency (HRD) scores, which were essential for clinical decision making.ConclusionTE-WGS proves to be a comprehensive approach in personalized oncology, matching the key biomarker detection capabilities of the established TSO500 panel. Additionally, TE-WGS uniquely identifies germline variants and genomic instability markers, offering additional clinical actions. Its adaptability and cost-effectiveness further underscore its clinical utility, making TE-WGS a valuable tool in personalized cancer treatment.

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Section: Discussionmentioning

confidence: 99%

Target-enhanced whole-genome sequencing (TE-WGS) shows clinical validity equivalent to commercially available targeted oncology panel

Lee,

Roh,

Park

et al. 2023

Preprint

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An innovative predictive model for cervical cancer constructed around a gene profile associated with cholesterol metabolism

Pu,

Jin,

Tang

et al. 2023

Environmental Toxicology

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Cholesterol metabolism is crucial for cell survival and cancer progression. The prognostic patterns of genes linked to cholesterol metabolism (CMAGs) in CESC, however, have received very little attention in research. From public databases, TCGA‐CESC cohorts with mRNA expression patterns and the accompanying clinical information of patients were gathered. Consensus clustering was used to find the molecular subtype connected to cholesterol metabolism. In the TCGA‐CESC cohort, a predictive risk model with 28 CMAGs was created using Lasso‐Cox regression. The function enrichment analysis between groups with high‐and low‐risk were investigated by employing GO, KEGG, and GSVA software. The immune cell infiltration was analyzed using ESTIMATE, CIBERSORT, and MCPCOUNTER methods. Finally, we select 7 genes in risk model for further multivariate Cox analysis, and ultimately a hub gene, CHIT1, was identified. Meanwhile, the function of CHIT1 was preliminarily verified in cell and mice tumor model. In conclusion, the abundance of the CHIT1 gene might be beneficial for forecasting the prognosis of CESC, demonstrating that cholesterol metabolism could be a promising treatment target for CESC.

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Associations between ADC histogram analysis values and tumor-micro milieu in uterine cervical cancer

Surov,

Borggrefe,

Höhn

et al. 2024

Cancer Imaging

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Background The complex interactions of the tumor micromilieu may be reflected by diffusion-weighted imaging (DWI) derived from the magnetic resonance imaging (MRI). The present study investigated the association between apparent diffusion coefficient (ADC) values and histopathologic features in uterine cervical cancer. Methods In this retrospective study, prebiopsy MRI was used to analyze histogram ADC-parameters. The biopsy specimens were stained for Ki-67, E-cadherin, vimentin and tumor-infiltrating lymphocytes (TIL, all CD45 positive cells). Tumor-stroma ratio (TSR) was calculated on routine H&E specimens. Spearman’s correlation analysis and receiver-operating characteristics curves were used as statistical analyses. Results The patient sample comprised 70 female patients (age range 32–79 years; mean age 55.4 years) with squamous cell cervical carcinoma. The interreader agreement was high ranging from intraclass coefficient (ICC) = 0.71 for entropy to ICC = 0.96 for ADCmedian. Several ADC-histogram parameters correlated strongly with the TSR. The highest correlation coefficient achieved p10 (r = -0.81, p < 0.0001). ADCmean can predict tumors with high TSR, AUC: 0.91, sensitivity: 0.91 (95% CI 0.77;0.96), specificity: 0.91 (95% CI 0.78;0.97). Several ADC-histogram parameters correlated slightly with the proliferation index Ki-67. No associations were found with TIL, E-Cadherin and vimentin. In well and moderately differentiated cancers, ADC histogram values showed stronger correlations with Ki-67 and TSR than in poorly differentiated tumors. Conclusion ADC values are strongly associated with tumor-stroma ratio. The ADC mean can be used to predict tumors with high TSR. Associations between histopathology and ADC values depend on tumor differentiation. ADC values show only weak associations with Ki-67 and none with TIL, vimentin and E-cadherin.

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Comprehensive genomic and immunohistochemical profiles and outcomes of immunotherapy in patients with recurrent or advanced cervical cancer

Cited by 3 publications

References 27 publications

Target-enhanced whole-genome sequencing (TE-WGS) shows clinical validity equivalent to commercially available targeted oncology panel

Target-enhanced whole-genome sequencing (TE-WGS) shows clinical validity equivalent to commercially available targeted oncology panel

An innovative predictive model for cervical cancer constructed around a gene profile associated with cholesterol metabolism

Associations between ADC histogram analysis values and tumor-micro milieu in uterine cervical cancer

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