Early squamous cell lung carcinoma: prognostic biomarkers for the many

Pezzella, Francesco

doi:10.1136/thoraxjnl-2018-212829

Cited by 3 publications

(3 citation statements)

References 18 publications

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“…Nowadays, we still have no approved targeted therapies and only depend on surgery, chemotherapy, or radiotherapy for the treatment of LUSC patients [31]. Surgical intervention for patients in the early stage and adjuvant postoperative treatment for those high-risk LUSC patients would truly improve their outcome [32]. Therefore, searching for prognostic and predictive biomarkers is of vital significance and a lot of studies have been performed.…”

Section: Discussionmentioning

confidence: 99%

Switched alternative splicing events as attractive features in lung squamous cell carcinoma

Wei

Cai

et al. 2022

Cancer Cell Int

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Background Alternative splicing (AS) plays important roles in transcriptome and proteome diversity. Its dysregulation has a close affiliation with oncogenic processes. This study aimed to evaluate AS-based biomarkers by machine learning algorithms for lung squamous cell carcinoma (LUSC) patients. Method The Cancer Genome Atlas (TCGA) database and TCGA SpliceSeq database were utilized. After data composition balancing, Boruta feature selection and Spearman correlation analysis were used for differentially expressed AS events. Random forests and a nested fivefold cross-validation were applied for lymph node metastasis (LNM) classifier building. Random survival forest combined with Cox regression model was performed for a prognostic model, based on which a nomogram was developed. Functional enrichment analysis and Spearman correlation analysis were also conducted to explore underlying mechanisms. The expression of some switch-involved AS events along with parent genes was verified by qRT-PCR with 20 pairs of normal and LUSC tissues. Results We found 16 pairs of splicing events from same parent genes which were strongly related to the splicing switch (intrapair correlation coefficient = − 1). Next, we built a reliable LNM classifier based on 13 AS events as well as a nice prognostic model, in which switched AS events behaved prominently. The qRT-PCR presented consistent results with previous bioinformatics analysis, and some AS events like ITIH5-10715-AT and QKI-78404-AT showed remarkable detection efficiency for LUSC. Conclusion AS events, especially switched ones from the same parent genes, could provide new insights into the molecular diagnosis and therapeutic drug design of LUSC.

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Section: Discussionmentioning

confidence: 99%

Switched alternative splicing events as attractive features in lung squamous cell carcinoma

Wei

Cai

et al. 2022

Cancer Cell Int

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“…It is indispensable to search for reliable prognostic biomarkers that can identify patients with a higher risk of poor survival. There are a lot of researches on the prognosis-related biomarkers of lung squamous cell carcinoma, but the applicability and accuracy of these indicators are not satisfactory (17). So far, clinical guidelines are still based on tumor staging (AJCC/UICC-TNM classification), which contains data on tumor burden (T), the presence of cancer cells in draining and regional lymph nodes (N), and evidence of metastasis (M) to assess disease stage and predict survival (18).…”

Section: Discussionmentioning

confidence: 99%

Identification of an Individualized Immune-Related Prognostic Risk Score in Lung Squamous Cell Cancer

Zhuang

Liu

et al. 2021

Front. Oncol.

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Background: Lung squamous cell carcinoma (LUSC) is one of the most common histological subtypes of non-small cell lung cancer (NSCLC), and its morbidity and mortality are steadily increasing. The purpose of this study was to study the relationship between the immune-related gene (IRGs) profile and the outcome of LUSC in patients by analyzing datasets from The Cancer Genome Atlas (TCGA).Methods: We obtained publicly available LUSC RNA expression data and clinical survival data from The Cancer Genome Atlas (TCGA), and filtered IRGs based on The ImmPort database. Then, we identified risk immune-related genes (r-IRGs) for model construction using Cox regression analysis and defined the risk score in this model as the immune gene risk index (IRI). Multivariate analysis was used to verify the independent prognostic value of IRI and its association with other clinicopathological features. Pearson correlation analysis was used to explore the molecular mechanism affecting the expression of IRGs and the correlation between IRI and immune cell infiltration.Results: We screened 15 r-IRGs for constructing the risk model. The median value of IRI stratified the patients and there were significant survival differences between the two groups (p = 4.271E-06). IRI was confirmed to be an independent prognostic factor (p < 0.001) and had a close correlation with the patients' age (p < 0.05). Interestingly, the infiltration of neutrophils or dendritic cells was strongly upregulated in the high-IRI groups (p < 0.05). Furthermore, by investigating differential transcription factors (TFs) and functional enrichment analysis, we explored potential mechanisms that may affect IRGs expression in tumor cells.Conclusion: In short, this study used 15 IRGs to build an effective risk prediction model, and demonstrated the significance of IRGs-based personalized immune scores in LUSC prognosis.

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“…Late diagnosis and the lack of actionable mutations are major contributors to the poor prognosis of LUSC. Numerous efforts have been invested in identifying molecular factors with either prognostic or predictive value in LUSC; however, no biomarker has been validated for use in standard clinical practice (10,17,18). Thus, there is an urgent need to identify prognostic and predictive biomarkers to improve outcomes of patients with LUSC.…”

Section: Introductionmentioning

confidence: 99%

Investigation on the potential of circulating tumor DNA methylation patterns as prognostic biomarkers for lung squamous cell carcinoma

Liu¹,

Feng²,

Hou³

et al. 2020

Transl Lung Cancer Res

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Background: Aberrant epigenetic modifications play a key role in lung tumorigenesis. In our study, we aimed to explore the clinical implications of baseline circulating tumor DNA (ctDNA) somatic and methylation profiles in patients with lung squamous cell carcinoma (LUSC).Methods: A total of 26 patients with LUSC of various stages were included in this study. Somatic mutations and methylation levels were profiled from the plasma-derived ctDNA obtained at the time of diagnosis using unique molecular identifier (UMI)-based targeted sequencing and bisulfite sequencing, respectively.The correlation between baseline ctDNA mutation and methylation profile, and overall survival (OS), were analyzed.Results: Somatic mutations were detected in 80.8% (20/26) of the patients. Patients harboring somatic mutations with maximum allelic fraction (maxAF) of >5% had significantly shorter OS compared to those with maxAF ≤5% (7.1 vs. 54.6 months; P=0.020). ctDNA methylation level was found to be strongly correlated with maxAF (Pearson correlation =0.934; P<0.001). Consistent with maxAF, higher methylation levels were also associated with poorer OS (hazard ratio =2.377; 95% CI: 1.283-4.405; P=0.006). Moreover, a total of 1,956 ctDNA methylation blocks were differentially methylated in patients with maxAF >0 (P<0.05). Least absolute shrinkage and selection operator (LASSO) regression analysis revealed a significant correlation between methylation signatures from 5 methylation blocks and OS (hazard ratio =183.20, 95% CI: 2.74-12,243.32; P=0.015). These 5 methylation blocks could serve as an alternative to maxAF and can be explored as prognostic biomarkers.Conclusions: Our study identified several ctDNA methylation blocks that can potentially predict the prognosis of LUSC at the time of diagnosis.

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Early squamous cell lung carcinoma: prognostic biomarkers for the many

Cited by 3 publications

References 18 publications

Switched alternative splicing events as attractive features in lung squamous cell carcinoma

Switched alternative splicing events as attractive features in lung squamous cell carcinoma

Identification of an Individualized Immune-Related Prognostic Risk Score in Lung Squamous Cell Cancer

Investigation on the potential of circulating tumor DNA methylation patterns as prognostic biomarkers for lung squamous cell carcinoma

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