A Predictive 7-Gene Assay and Prognostic Protein Biomarkers for Non-small Cell Lung Cancer

Guo, Nancy Lan; Dowlati, Afshin; Raese, Rebecca; Dong, Chunlin; Chen, Guoan; Beer, David G.; Shaffer, J. Scott; Singh, Salvi; Bokhary, Ujala; Liu, Lin; Howington, John A.; Hensing, Thomas A.; Qian, Yong

doi:10.1016/j.ebiom.2018.05.025

Cited by 18 publications

(48 citation statements)

References 48 publications

(87 reference statements)

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“…To date, physicians do not have a precise tool to identify patients with resectable NSCLC that are likely to develop tumor recurrence or metastasis. Our previous study developed a 7-gene assay for NSCLC prognosis and prediction of chemotherapeutic benefits [ 6 ]. The ability of this gene assay to identify those at a high risk for recurrence or metastasis would potentially inform selection of specific adjuvant chemotherapy for these patients.…”

Section: Introductionmentioning

confidence: 99%

Molecular Analysis of ZNF71 KRAB in Non-Small-Cell Lung Cancer

Mohamed

Dukhlallah

et al. 2021

IJMS

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Our previous study found that zinc finger protein 71 (ZNF71) mRNA expression was associated with chemosensitivity and its protein expression was prognostic of non-small-cell lung cancer (NSCLC). The Krüppel associated box (KRAB) transcriptional repression domain is commonly present in human zinc finger proteins, which are linked to imprinting, silencing of repetitive elements, proliferation, apoptosis, and cancer. This study revealed that ZNF71 KRAB had a significantly higher expression than the ZNF71 KRAB-less isoform in NSCLC tumors (n = 197) and cell lines (n = 117). Patients with higher ZNF71 KRAB expression had a significantly worse survival outcome than patients with lower ZNF71 KRAB expression (log-rank p = 0.04; hazard ratio (HR): 1.686 [1.026, 2.771]), whereas ZNF71 overall and KRAB-less expression levels were not prognostic in the same patient cohort. ZNF71 KRAB expression was associated with epithelial-to-mesenchymal transition (EMT) in both patient tumors and cell lines. ZNF71 KRAB was overexpressed in NSCLC cell lines resistant to docetaxel and paclitaxel treatment compared to chemo-sensitive cell lines, consistent with its association with poor prognosis in patients. Therefore, ZNF71 KRAB isoform is a more effective prognostic factor than ZNF71 overall and KRAB-less expression for NSCLC. Functional analysis using CRISPR-Cas9 and RNA interference (RNAi) screening data indicated that a knockdown/knockout of ZNF71 did not significantly affect NSCLC cell proliferation in vitro.

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Section: Introductionmentioning

confidence: 99%

Molecular Analysis of ZNF71 KRAB in Non-Small-Cell Lung Cancer

Mohamed

Dukhlallah

et al. 2021

IJMS

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“…Lung cancer (LC) is one of the most common malignant tumors in the world (1,2). According to data compiled by the American Cancer Society, there were 234,030 estimated new LC cases and 154,050 estimated LC-associated mortalities in the USA in 2018 (3).…”

Section: Introductionmentioning

confidence: 99%

The expression, significance and function of cancer susceptibility candidate�9 in lung squamous cell carcinoma: A bioinformatics and in�vitro investigation

Guo

Zeng

et al. 2019

Int J Oncol

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The cancer susceptibility candidate 9 (CASC9) gene has been reported to exert an oncogenic effect in several types of cancer. However, its role in lung squamous cell carcinoma (LUSC) is unknown. Therefore, the present study examined the expression of CASC9 in LUSC and non-cancer tissues by reverse transcription-quantitative polymerase chain reaction assays and by data mining of high-throughput public databases, including The Cancer Genome Atlas, the Gene Expression Omnibus, ArrayExpress and the Cancer Cell Line Encyclopedia. In vitro experiments were conducted to investigate the effects of CASC9 on the viability and the proliferation of LUSC cells. Furthermore, consulting the alteration status of CASC9 in LUSC from cBioPortal, functional enrichment analysis of co-expressed genes, prediction of potential transcription factors, and inspection of adjacent protein-coding genes were conducted to explore the potential molecular mechanism of CASC9 in LUSC. The results revealed that CASC9 was overexpressed in LUSC tissue, and significantly associated with the malignant progression of LUSC. In vitro experiments demonstrated that CASC9 knockdown by RNA interference attenuated the viability and proliferation of LUSC cells. Multiple copies of CASC9 gene were detected in 4 of 179 available sequenced LUSC cases. A functional enrichment analysis of 200 co-expressed genes indicated that these genes were significantly associated with terms, including 'cell-cell junction organization', 'desmosome organization', 'epidermis development', 'Hippo signaling pathway', 'pathogenic Escherichia coli infection' and 'PID HIF1 TF pathway'. Three genes, Fos-related antigen 2 (FOSL2), SWI/SNF complex subunit SMARCC2, and transcription factor COE1 (EBF1), were predicted by lncRNAMap to be associated with CASC9. Among these, the expression of FOSL2 and EBF1 was positively and negatively correlated with the expression of CASC9, respectively. Two adjacent protein-coding genes, cysteine-rich secretory protein LCCL domain-containing 1 and hepatocyte nuclear factor 4-γ, were also positively correlated with CASC9 expression. In conclusion, the present data suggest that CASC9 serves as an oncogene in LUSC and may be a promising target for alternative therapeutic options for patients with this condition.

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“…A predictive 7-gene assay and prognostic protein biomarkers were established for improving NSCLC treatment. These findings could divide cancer patients into high or low risk group [ 12 ]. However, these authors did not use clinical and pathological information in their studies.…”

Section: Introductionmentioning

confidence: 99%

A molecular and staging model predicts survival in patients with resected non-small cell lung cancer

et al. 2018

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BackgroundThe current TNM staging system is far from perfect in predicting the survival of individual non-small cell lung cancer (NSCLC) patients. In this study, we aim to combine clinical variables and molecular biomarkers to develop a prognostic model for patients with NSCLC.MethodsCandidate molecular biomarkers were extracted from the Gene Expression Omnibus (GEO), and Cox regression analysis was performed to determine significant prognostic factors. The survival prediction model was constructed based on multivariable Cox regression analysis in a cohort of 152 NSCLC patients. The predictive performance of the model was assessed by the Area under the Receiver Operating Characteristic Curve (AUC) and Kaplan–Meier survival analysis.ResultsThe survival prediction model consisting of two genes (TPX2 and MMP12) and two clinicopathological factors (tumor stage and grade) was developed. The patients could be divided into either high-risk group or low-risk group. Both disease-free survival and overall survival were significantly different among the diverse groups (P < 0.05). The AUC of the prognostic model was higher than that of the TNM staging system for predicting survival.ConclusionsWe developed a novel prognostic model which can accurately predict outcomes for patients with NSCLC after surgery.Electronic supplementary materialThe online version of this article (10.1186/s12885-018-4881-9) contains supplementary material, which is available to authorized users.

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A Predictive 7-Gene Assay and Prognostic Protein Biomarkers for Non-small Cell Lung Cancer

Cited by 18 publications

References 48 publications

Molecular Analysis of ZNF71 KRAB in Non-Small-Cell Lung Cancer

Molecular Analysis of ZNF71 KRAB in Non-Small-Cell Lung Cancer

The expression, significance and function of cancer susceptibility candidate�9 in lung squamous cell carcinoma: A bioinformatics and in�vitro investigation

A molecular and staging model predicts survival in patients with resected non-small cell lung cancer

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