Pre-treatment Serum HE4 Level as a Novel Independent Prognostic Biomarker for Uterine Cervical Carcinoma Patients

Bignotti, Eliana; Zanotti, Laura; Todeschini, Paola; Zizioli, Valentina; Romani, Chiara; Capoferri, Davide; Tognon, Germana; Sartori, Enrico; Calza, Stefano; Odicino, Franco; Ravaggi, Antonella

doi:10.3389/fonc.2020.584022

Cited by 5 publications

(6 citation statements)

References 28 publications

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“…The results demonstrated that GTSF1L and GNG8 exhibited a gradually decreasing tendency along with the disease progression, and GTSF1L showed greater expression disparity (Figure 9A). CA125 (MUC16), CEA (CEACAM5), and HE4 (WFDC2) are clinically established diagnostic and prognostic markers of CESC; high levels of these biomarkers suggest cancer progression and poor prognosis (18,19). Here, we found that the expression level of GTSF1L in CESC displayed a significantly negative relationship with these biomarkers (Figures 9B and S12A), which was relatively consistent with the better prognosis observed in the GTSF1L-high patient group.…”

Section: The Role Of Gtsf1l In Immune Contexture and Clinical Practicesupporting

confidence: 81%

Development of a Novel Immune Infiltration-Based Gene Signature to Predict Prognosis and Immunotherapy Response of Patients With Cervical Cancer

Zhang

et al. 2021

Front. Immunol.

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Predictive models could indicate the clinical outcome of patients with carcinoma. Cervical cancer is one of the most frequently diagnosed female malignancies. Herein, we proposed an immune infiltration-related gene signature that predicts prognosis of patients with cervical cancer and depicts the immune landscape as well. We utilized the transcriptome data of The Cancer Genome Atlas (TCGA) and estimated the infiltration level of 28 immune cell types. We screened out four immune cell types conducive to patient survival and recognized their shared differentially expressed genes (DEGs). Four core genes (CHIT1, GTSF1L, PLA2G2D, and GNG8) that composed the ultimate signature were identified via univariate and multivariate Cox regression. The optimal model we built up could distinguish patients with cervical cancer into high-score and low-score subgroups. These two subgroups showed disparity in aspects of patient survival, immune infiltration landscape, and response to immune checkpoint inhibitors. Additionally, we found that GTSF1L was decreased gradually along with the severity of cervical lesions, and its potential role in immune contexture and clinical practice were also demonstrated. Our results suggested that the Immunoscore based on four immune-related genes could serve as a supplementary criterion to effectively foresee the survival outcome, tumor infiltration status, and immunotherapy efficacy of cervical cancer patients.

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Section: The Role Of Gtsf1l In Immune Contexture and Clinical Practicesupporting

confidence: 81%

Development of a Novel Immune Infiltration-Based Gene Signature to Predict Prognosis and Immunotherapy Response of Patients With Cervical Cancer

Zhang

et al. 2021

Front. Immunol.

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“…A more recent study evaluating the role of pre-treatment serum HE4 levels in cervical cancer reported that serum HE4 could be a preoperative tumor biomarker of poor prognosis in cervical cancer. 29 Consistent with our own results, this study also demonstrated that higher levels of serum HE4 correlate with advanced stage, larger tumor size, and high tumor grade, while no significant association was found with LVSI, PM involvement, and LN involvement, which is not consistent with our study.…”

Section: Discussionsupporting

confidence: 79%

“…28,35 In other previous studies, serum HE4 levels were higher in cervical cancer patients compared to healthy controls, but lower than ovarian cancer patients, showing similar results to our study. 28,29 This study has several limitations. First, the existence of underlying selection bias is possible due to the retrospective design.…”

Section: Discussionmentioning

confidence: 96%

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Serum Human Epididymis Protein 4 as a Prognostic Marker in Cervical Cancer

Suh

Kim

et al. 2022

Cancer Control

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Objectives The objective is to evaluate the prognostic value of serum human epididymis protein 4 (HE4) as a tumor marker in patients with cervical cancer. Methods Sixty-seven patients with cervical cancer treated at Seoul National University Bundang Hospital from September 2014 to May 2018 were retrospectively reviewed. Serum HE4 levels were measured by immunoassay before starting primary treatment. A mean serum HE4 level of 72.6 pmol/L was used to divide the patients into low and high HE4 groups. Patient characteristics, clinicopathological variables, and survival outcomes were compared between the two groups. Results The low and high HE4 groups included 55 (82.1%) and 12 (17.9%) patients at diagnosis, respectively. Higher HE4 levels were significantly associated with older age at diagnosis (age <50: .0% vs age ≥50: 100.0%; P = .002), menopause (premenopause: 8.3% vs postmenopause: 91.7%; P = .009), higher FIGO stage (stage I–II: 33.3% vs III–IV: 66.7%; P = .017), large tumor size (<4.0 cm: 41.7% vs ≥4.0 cm: 58.3%; P = .029), positive lymph node metastasis (negative: 41.7% vs positive: 58.3%; P = .049), and involvement of the parametrium (negative: 25.0% vs positive: 75.0%; P = .002). Higher HE4 level was a predictive factor for worse overall survival but not for progression-free survival. Elevated HE4 levels were not independent factors for the prediction of either overall survival or progression-free survival. Subgroup analysis by histological type revealed similar results for patients with squamous cell carcinoma. Conclusions High levels of HE4 expression correlated with poor overall survival, indicating that elevated HE4 levels are associated with a poor prognosis for patients with cervical cancer.

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“…Currently, alterations in CA125 and SCC antigen levels are more likely to predict CC outcomes [15,16]. Moreover, HE4 is a prognostic marker for survival in individuals who have high risk of CC [17]. Recent studies have shown that serum SCC is a better biomarker, with a sensitivity of 80% in patients with CC [18,19].…”

Section: Discussionmentioning

confidence: 99%

Serum Level of Tumor-Specific Growth Factor in Patients with Cervical Cancer and Its Potential Prognostic Role

Wu¹,

Qu²,

Shen³

et al. 2022

Oncologie

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Background: Tumor-specific growth factor (TSGF) is associated with invasion and metastasis of various malignancies and adverse clinical outcomes. TSGF is also highly expressed in cervical cancer (CC), but its clinical value is unclear. Materials and Methods: Serum samples from malignancies, including CC, non-Hodgkin's lymphoma (NHL), nasopharyngeal carcinoma (NPC), colorectal cancer (CRC), lung cancer (LCA), ovarian cancer (OC), breast cancer (BC), gastric carcinoma (GC), and pancreatic cancer (PC) were collected, and TSGF was detected using a chemiluminescence assay. The patients with CC were followed-up over five years, and their clinicopathological parameters were analyzed. Meanwhile, the pre-and post-treatment TSGF levels of patients with CC were compared. The predictive and prognostic roles of TSGF were evaluated in the patients with CC using Kaplan-Meier survival curves, multivariate COX analyses, and ROC curves. Results: CC, CRC, and OC patients had higher serum TSGF than the healthy population (P < 0.05), and the serum TSGF of patients with CC was higher than that of other cancers (P < 0.05). Clinicopathologic analysis showed that TSGF was linked to CC tumor size, tumor invasion depth, histologic grade, and the International Federation of Gynecology and Obstetrics (FIGO) stage, and TSGF had a high sensitivity of 56%. The post-treatment TSGF in patients with CC was significantly decreased (P < 0.05). Kaplan-Meier survival curves identified high TSGF as a significant poor predictor of metastasis-free, recurrence-free, and overall survival (OS). Multivariate COX analyses showed that TSGF was an independent prognostic factor for OS rate. The ROC curve revealed that serum TSGF levels had a significant ability to predict recurrence, while the cut-off value for TSGF was 66.94 U/mL. Serum TSGF levels notably decreased in post-therapeutic patients and gradually with treatment progress. Conclusions: Serum TSGF may be a novel potential indicator for predicting prognosis and recurrence after surgery and adjuvant therapy in patients with CC.

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Pre-treatment Serum HE4 Level as a Novel Independent Prognostic Biomarker for Uterine Cervical Carcinoma Patients

Cited by 5 publications

References 28 publications

Development of a Novel Immune Infiltration-Based Gene Signature to Predict Prognosis and Immunotherapy Response of Patients With Cervical Cancer

Development of a Novel Immune Infiltration-Based Gene Signature to Predict Prognosis and Immunotherapy Response of Patients With Cervical Cancer

Serum Human Epididymis Protein 4 as a Prognostic Marker in Cervical Cancer

Serum Level of Tumor-Specific Growth Factor in Patients with Cervical Cancer and Its Potential Prognostic Role

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