The Overexpression of FEN1 and RAD54B May Act as Independent Prognostic Factors of Lung Adenocarcinoma

Hwang, Jau-Chung; Sung, Wen‐Wei; Tu, Hung-Pin; Hsieh, Kun-Chou; Yeh, Chung-Min; Chen, Chih‐Jung; Tai, Hui-Chun; Hsu, Chao‐Tien; Shieh, Grace S.; Chang, Jan-Gowth; Yeh, Kun-Tu; Liu, Ta-Chih

doi:10.1371/journal.pone.0139435

Cited by 28 publications

(29 citation statements)

References 42 publications

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“…Previous studies have reported that overexpression of FEN1 is positively correlated with poor prognosis of nonsmall-cell lung cancer [16] and breast cancer [17], as well as lung adenocarcinoma [22]. In addition, the gene has been proposed as a prognostic biomarker for cancer.…”

Section: Discussionmentioning

confidence: 99%

Upregulation of FEN1 Is Associated with the Tumor Progression and Prognosis of Hepatocellular Carcinoma

Zhang

Liu

et al. 2020

Disease Markers

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Background. Studies show that patients with hepatocellular carcinoma (HCC) have poor prognosis, particularly when patients are diagnosed at late stages of the disease development. The flap endonuclease 1 (FEN1) gene is overexpressed in multiple malignant tumors and may promote tumor aggressiveness. However, its expression profile and functional roles in HCC are still unclear. Here, we evaluated the molecular mechanisms of FEN1 in HCC. Methods. The expression of FEN1 in HCC was evaluated using HCC mRNA expression data from TCGA and GEO databases. The expression of FEN1 was also confirmed by immunohistochemistry (IHC) using a tissue microarray (TMA) cohort with a total of 396 HCC patients. Kaplan-Meier analysis and univariate and multivariate Cox regression analyses were used to determine the correlation between FEN1 expression and survival rate of HCC patients. The molecular mechanism and biological functions of FEN1 in HCC were predicted using functional and pathway enrichment analysis in vitro experiments. Results. FEN1 was overexpressed in multiple HCC cohorts at both mRNA and protein levels. The receiver operating characteristic (ROC) curve showed that FEN1 can serve as a diagnostic predictor of HCC. Meanwhile, patients with high FEN1 expression levels showed lower overall survival (OS) and relapse-free survival (RFS) rates than those with low FEN1 expression. More importantly, we found that FEN1 elevation was an independent prognostic factor for OS and RFS in HCC patients based on univariate and multivariate analyses, indicating that FEN1 might be a potential prognostic marker in HCC. Furthermore, knocking down FEN1 resulted in suppressed cell proliferation and migration in vitro. This could have been due to regulation expressions of c-Myc, survivin, and cyclin D1 genes, indicating that FEN1 may function as an oncogene through its role in the cell cycle and DNA replication pathway. Conclusion. Our study indicated that high FEN1 expression might function as a biomarker for diagnosis and prognosis. In addition, the study confirms that FEN1 is an oncogene in HCC progression.

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Section: Discussionmentioning

confidence: 99%

Upregulation of FEN1 Is Associated with the Tumor Progression and Prognosis of Hepatocellular Carcinoma

Zhang

Liu

et al. 2020

Disease Markers

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“…RAD54B is a known HR protein 25 and its elevated expression is associated with poor prognosis in colorectal 26 and lung 27 cancers. Consistently, our data in EAC shows that elevated RAD54B expression contributes to increased HR activity and genomic instability, and correlates with poor survival.…”

Section: Discussionmentioning

confidence: 99%

Integrated genomics and comprehensive validation reveal novel drivers of genomic evolution in esophageal adenocarcinoma

Kumar

Buon

Talluri

et al. 2020

Preprint

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Identification of genes driving genomic evolution can provide novel targets for cancer treatment and prevention. Here we show identification of a genomic instability gene signature, using an integrated genomics approach. Elevated expression of this signature correlated with poor survival in esophageal adenocarcinoma (EAC) as well as three other human cancers. Knockout and overexpression screens confirmed the relevance of this signature to genomic instability. Indepth evaluation of TTK (a kinase), TPX2 (spindle assembly factor) and RAD54B (recombination protein) further confirmed their role in genomic instability and tumor growth. Mutational signatures identified by whole genome sequencing and functional studies demonstrated that DNA damage and homologous recombination were common mechanisms of genomic instability induced by these genes. Consistently, a TTK inhibitor impaired EAC cell growth in vivo, and increased chemotherapy-induced cytotoxicity while inhibiting genomic instability in surviving cells. Thus inhibitors of TTK and other genes identified in this study have potential to inhibit/delay genomic evolution and tumor growth. Such inhibitors also have potential to increase chemotherapy-induced cytotoxicity while reducing its harmful genomic impact in EAC and possibly other cancers.

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“…The clinicopathological features collected from the established database included risk factors, histological type, differentiation, and TNM stage. The histological diagnoses had been previously confirmed by two pathologists [18]. Patients with missing data or tissue loss during the IHC staining procedure were excluded from the study to reduce the bias from missing data.…”

Section: Patientsmentioning

confidence: 99%

“…The IHC staining was performed at the Department of Surgical Pathology, Changhua Christian Hospital using anti-human KLF17 antibody (abcam-84196; 1:100 dilution), as described previously [18,19]. Immunoreactivity was scored by the pathologists using a previously described scoring protocol [19,20].…”

Section: Immunohistochemical Staining Of Klf17mentioning

confidence: 99%

“…A final consensus was obtained for each score by having all evaluators view the specimens simultaneously through a multi-headed microscope (Olympus BX51 10-headed microscope). The immunoreactivity scores were defined as cell staining intensity (0-3) multiplied by the percentage of stained cells (0-100%), leading to scores from 0 to 300 [18,19].…”

Section: Immunohistochemical Staining Of Klf17mentioning

confidence: 99%

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Overexpression of KLF17 Predicts a Favorable Prognosis in Patients with Oral Squamous Cell Carcinoma: A Retrospective Study

et al. 2020

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Background and Objectives: Patients with oral squamous cell carcinoma (OSCC), a common malignancy in Asian countries, have a poor prognosis. We investigated the role of Krüppel-like factor 17 (KLF17) and its prognostic significance in OSCC. Materials and Methods: KLF17 expression was measured by immunohistochemical staining of specimens from 283 patients with OSCC. We analyzed correlations between KLF17 expression and clinicopathologic features and between KLF17 expression and overall survival. The prognostic value of KLF17 was tested using Kaplan–Meier analysis and Cox proportional hazard models. Results: Among the 283 patients, high KLF17 expression was significantly associated with an early OSCC stage and low T-value (p = 0.033 and p = 0.036, respectively). The five-year survival rates were better in patients with high KLF17 expression than with low expression (66.5% and 49.6%, respectively). The prognostic role of KLF17 was further confirmed through multivariate analysis (hazard ratio 1.506, 95% confidence interval 1.034–2.191, p = 0.033). The prognostic value was more significant in patients with a history of betel quid chewing or with a low T-value. Conclusions: High KLF17 expression can serve as a marker for a favorable prognosis in patients with OSCC. The prognostic role of KLF17 is more significant in patients with a history of betel quid chewing or a low T-value.

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The Overexpression of FEN1 and RAD54B May Act as Independent Prognostic Factors of Lung Adenocarcinoma

Cited by 28 publications

References 42 publications

Upregulation of FEN1 Is Associated with the Tumor Progression and Prognosis of Hepatocellular Carcinoma

Upregulation of FEN1 Is Associated with the Tumor Progression and Prognosis of Hepatocellular Carcinoma

Integrated genomics and comprehensive validation reveal novel drivers of genomic evolution in esophageal adenocarcinoma

Overexpression of KLF17 Predicts a Favorable Prognosis in Patients with Oral Squamous Cell Carcinoma: A Retrospective Study

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