A 4-gene signature predicts prognosis of uterine serous carcinoma

Chen, Hui; Qin, Peihua; Xiong, Hanzhen; Chen, Ruichao; Zhang, Minfen; Jiang, Qingping

doi:10.1186/s12885-021-07834-4

Cited by 5 publications

(7 citation statements)

References 51 publications

(18 reference statements)

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“…Finally, on multivariable Cox proportional hazards regression analysis, the presence of recurrence or metastases to the liver and/or the peritoneum were independently associated with shorter OS regardless of their mutational status, race, ethnicity or other sites of recurrence or metastases. Various studies attempted to build predictive survival models for USC, including a study by Chen et al on 110 women with USC which showed that a combination of mutated genes, a 4-gene signature, was predictive of OS (42). Differently from our study, their model did not include sites of metastases or survival as potential predictors.…”

Section: Discussioncontrasting

confidence: 58%

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Uterine serous carcinoma: assessing association between genomics and patterns of metastasis

et al. 2023

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BackgroundUterine serous carcinoma (USC) is an aggressive subtype of endometrial carcinoma which has been increasing at alarming rates, particularly among Asian, Hispanic and Black women. USC has not been well characterized in terms of mutational status, pattern of metastases and survival.ObjectiveTo investigate the association between sites of recurrence and metastases of USC, mutational status, race, and overall survival (OS).MethodsThis single-center retrospective study evaluated patients with biopsy-proven USC that underwent genomic testing between January 2015 and July 2021. Association between genomic profile and sites of metastases or recurrence was performed using χ2 or Fisher’s exact test. Survival curves for ethnicity and race, mutations, sites of metastasis/recurrence were estimated using the Kaplan-Meier method and compared with log-rank test. Cox proportional hazard regression models were used to examine the association between OS with age, race, ethnicity, mutational status, and sites of metastasis/recurrence. Statistical analyses were performed using SAS Software Version 9.4.ResultsThe study included 67 women (mean age 65.8 years, range 44-82) with 52 non-Hispanic women (78%) and 33 Black women (49%). The most common mutation was TP53 (55/58 women, 95%). The peritoneum was the most common site of metastasis (29/33, 88%) and recurrence (8/27, 30%). PR expression was more common in women with nodal metastases (p=0.02) and non-Hispanic women (p=0.01). ERBB2 alterations were more common in women with vaginal cuff recurrence (p=0.02), while PIK3CA mutation was more common in women with liver metastases (p=0.048). ARID1A mutation and presence of recurrence or metastases to the liver were associated with lower OS (Hazard Ratio (HR): 31.87; 95%CI: 3.21, 316.9; p<0.001 and HR: 5.66; 95%CI: 1.2, 26.79; p=0.01, respectively). In the bivariable Cox model, the presence of metastasis/recurrence to the liver and/or the peritoneum were both independent significant predictors of OS (HR: 9.8; 95%CI: 1.85-52.7; p=0.007 and HR: 2.7; 95%CI: 1.02-7.1; p=0.04, respectively).ConclusionsTP53 is often mutated in USC, which most commonly metastasize and recur in the peritoneum. OS was shorter in women with ARID1A mutations and with metastasis/recurrence to the liver. The presence of metastasis/recurrence to liver and/or peritoneum were independently associated with shorter OS.

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Section: Discussioncontrasting

confidence: 58%

“…Various studies attempted to build predictive survival models for USC, including a study by Chen et al. on 110 women with USC which showed that a combination of mutated genes, a 4-gene signature, was predictive of OS ( 42 ). Differently from our study, their model did not include sites of metastases or survival as potential predictors.…”

Section: Discussionmentioning

confidence: 99%

Uterine serous carcinoma: assessing association between genomics and patterns of metastasis

et al. 2023

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“…Loss of KRT23 affects the cell cycle, DNA replication, recombination, and repair (Birkenkamp-Demtröder et al, 2013). Evidence from previous studies has indicated that KRT23 influences the proliferation, migration, and prognosis of cancer (Odena et al, 2016;Zhang et al, 2017;Chen et al, 2021). ANGPT2 is a ligand for TIE1-TIE2 signaling involved in the development and maintenance of blood and lymphatic vessels (Smeland et al, 2021).…”

Section: Discussionmentioning

confidence: 99%

Nine-gene signature and nomogram for predicting survival in patients with head and neck squamous cell carcinoma

et al. 2022

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Background: Head and neck squamous cell carcinomas (HNSCCs) are derived from the mucosal linings of the upper aerodigestive tract, salivary glands, thyroid, oropharynx, larynx, and hypopharynx. The present study aimed to identify the novel genes and pathways underlying HNSCC. Despite the advances in HNSCC research, diagnosis, and treatment, its incidence continues to rise, and the mortality of advanced HNSCC is expected to increase by 50%. Therefore, there is an urgent need for effective biomarkers to predict HNSCC patients’ prognosis and provide guidance to the personalized treatment.Methods: Both HNSCC clinical and gene expression data were abstracted from The Cancer Genome Atlas (TCGA) database. Intersecting analysis was adopted between the gene expression matrix of HNSCC patients from TCGA database to extract TME-related genes. Differential gene expression analysis between HNSCC tissue samples and normal tissue samples was performed by R software. Then, HNSCC patients were categorized into clusters 1 and 2 via NMF. Next, TME-related prognosis genes (p < 0.05) were analyzed by univariate Cox regression analysis, LASSO Cox regression analysis, and multivariate Cox regression analysis. Finally, nine genes were selected to construct a prognostic risk model and a prognostic gene signature. We also established a nomogram using relevant clinical parameters and a risk score. The Kaplan–Meier curve, survival analysis, time-dependent receiver operating characteristic (ROC) analysis, decision curve analysis (DCA), and the concordance index (C-index) were carried out to assess the accuracy of the prognostic risk model and nomogram. Potential molecular mechanisms were revealed by gene set enrichment analysis (GSEA). Additionally, gene correlation analysis and immune cell correlation analysis were conducted for further enriching our results.Results: A novel HNSCC prognostic model was established based on the nine genes (GTSE1, LRRN4CL, CRYAB, SHOX2, ASNS, KRT23, ANGPT2, HOXA9, and CARD11). The value of area under the ROC curves (AUCs) (0.769, 0.841, and 0.816) in TCGA whole set showed that the model effectively predicted the 1-, 3-, and 5-year overall survival (OS). Results of the Cox regression assessment confirmed the nine-gene signature as a reliable independent prognostic factor in HNSCC patients. The prognostic nomogram developed using multivariate Cox regression analysis showed a superior C-index over other clinical signatures. Also, the calibration curve had a high level of concordance between estimated OS and the observed OS. This showed that its clinical net can precisely estimate the one-, three-, and five-year OS in HNSCC patients. The gene set enrichment analysis (GSEA) to some extent revealed the immune- and tumor-linked cascades.Conclusion: In conclusion, the TME-related nine-gene signature and nomogram can effectively improve the estimation of prognosis in patients with HNSCC.

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“…SOX9 was significantly more expressed in the UCS than in normal control endometrial tissue in USC of TCGA and GETX datasets. Meanwhile, a 4-gene ( KRT23 , CXCL1 , SOX9 , and ABCA10 ) signature robustly predicts OS and recurrence-free survival(RFS) of USC ( 81 ). Furthermore, the expression of both mRNA and protein of SOX9 was significantly higher in tumor tissues than in paired adjacent tissues.…”

Section: Endometrial Cancermentioning

confidence: 99%

SOX9: Advances in Gynecological Malignancies

Chen

Wen

et al. 2021

Front. Oncol.

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Transcription factors of the SOX family were first discovered in mammals in 1990. The sex-determining region Y box 9 belongs to the SOX transcription factor family. It plays an important role in inducing tissue and cell morphogenesis, survival, and many developmental processes. Furthermore, it has been shown to be an oncogene in many tumors. Gynecological malignancies are tumors that occur in the female reproductive system and seriously threaten the lives of patients. Common gynecological malignancies include ovarian cancer, cervical cancer, and endometrial cancer. So far, the molecular mechanisms related to the incidence and development of gynecological malignancies remain unclear. This makes it particularly important to discover their common causative molecule and thus provide an effective therapeutic target. In recent years, studies have found that multiple mechanisms are involved in regulating the expression of the sex-determining region Y box 9, leading to the occurrence and development of gynecological malignancies. In this review, we discuss the prognostic value of SOX9 expression and the potential of targeting SOX9 for gynecological malignancy treatment. We also discuss progress regarding the role of SOX9 in gynecological malignancy pathogenesis through its mediation of important mechanisms, including tumor initiation and proliferation, apoptosis, migration, invasion, chemoresistance, and stem cell maintenance.

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A 4-gene signature predicts prognosis of uterine serous carcinoma

Cited by 5 publications

References 51 publications

Uterine serous carcinoma: assessing association between genomics and patterns of metastasis

Uterine serous carcinoma: assessing association between genomics and patterns of metastasis

Nine-gene signature and nomogram for predicting survival in patients with head and neck squamous cell carcinoma

SOX9: Advances in Gynecological Malignancies

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