The Prognostic Value of P73 Overexpression in Colorectal Carcinoma

Toumi, Amira Arfaoui; Hadj, Olfa El Amine El; Mahmoud, Lilia Kriaa Ben; Hmida, Abd el Majid Ben; Chaar, Ines; Gharbi, Lassad; Mzabi, Sabeh; Bouraoui, Saâdia

doi:10.1097/pai.0b013e3181bcb2da

Cited by 8 publications

(3 citation statements)

References 29 publications

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“…ΔNp73 has also been detected in EVs from CRC patients and associated with a worse outcome [ 18 ]. Interestingly, although TAp73 presents tumor suppressor abilities similar to those described for TP53 , it has been described as overexpressed in many human tumors including CRC and associated with poorer survival [ 15 , 41 , 42 , 43 , 44 ]. Remarkably, its status in EVs from cancer patients has not been tested yet.…”

Section: Discussionmentioning

confidence: 99%

ΔNp73, TAp73 and Δ133p53 Extracellular Vesicle Cargo as Early Diagnosis Markers in Colorectal Cancer

Rodríguez-Cobos

Viñal

Povés

et al. 2021

Cancers

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The early diagnosis of colorectal cancer is a key factor in the overall survival of the patients. The actual screening programs include different approaches with significant limitations such as unspecificity, high invasiveness, and detection at late stages of the disease. The specific content of extracellular vesicles derived from malignant cells may represent a non-invasive technique for the early detection of colorectal cancer. Here, we studied the mRNA levels of ΔNp73, TAp73, and Δ133p53 in plasma-derived extracellular vesicles from healthy subjects (n = 29), individuals with premalignant lesions (n = 49), and colorectal cancer patients (n = 42). Extracellular vesicles’ ΔNp73 levels were already significantly high in subjects with premalignant lesions. Δ133p53 levels were statistically increased in colorectal cancer patients compared to the other two groups and were associated with patients’ survival. Remarkably, TAp73 mRNA was not detected in any of the individuals. The evaluation of ΔNp73, Δ133p53 and CEA sensitivity, specificity and AUC values supports ΔNp73 as a better early diagnosis biomarker and CEA as the best to identify advanced stages. Thus, low levels of CEA and a high content of ΔNp73 may identify in screening programs those individuals at higher risk of presenting a premalignant lesion. In addition, Δ133p53 emerges as a potential prognosis biomarker in colorectal cancer.

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Section: Discussionmentioning

confidence: 99%

ΔNp73, TAp73 and Δ133p53 Extracellular Vesicle Cargo as Early Diagnosis Markers in Colorectal Cancer

Rodríguez-Cobos

Viñal

Povés

et al. 2021

Cancers

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“…Most studies have shown that positive immunohistochemical staining TP73 was associated with worse clinical outcome in extrahepatic bile duct carcinoma [19], cholangiocellular carcinoma [20], hepatocellular carcinoma [39,43], colorectal cancer [26,44], ovarian cancer [28] and esophageal squamous cell carcinoma [36]. However, we further evaluated the association between TP73 expression and overall survival of cervical cancer patients in TCGA database, and found that TP73 expression was positively correlated with overall survival time in cervical cancer patients.…”

Section: Discussionmentioning

confidence: 99%

TP73 is a credible biomarker for predicting clinical progression and prognosis in cervical cancer patients

Guo²

2019

Bioscience Reports

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Tumor protein p73 (TP73) has been reported to be dysregulated in various types of human cancer and associated with clinical progression and outcome. Owing to the lack of reports on the correlation between TP73 protein expression and clinicopathologic features of cervical cancer, the aim of our research was to explore the clinical and prognostic significance of TP73 protein expression in cervical cancer patients. In our study, TP73 protein expression was detected by immunochemistry in 118 paraffin-embedded cervical cancer tissue specimens and 40 paraffin-embedded normal cervical epithelium tissue specimens. In the results, we found cervical cancer tissues exhibited high TP73 expression in comparison with normal cervical epithelium tissues, which was consistent with the expression status of TP73 in The Cancer Genome Atlas (TCGA) database. Furthermore, we analyzed the relationships between TP73 expression and clinicopathologic features through using the chi-square test or Fisher’s exact test, and found high expression of TP73 was markedly associated with early clinical stage, less lymph node metastasis, absent distant metastasis, squamous cell carcinoma and favorable histological grade. The Kaplan–Meier method and log-rank test were performed based on the expression level of TP73 in a cervical cancer cohort from the TCGA database, and showed that TP73 expression was positively correlated with overall survival time in cervical cancer patients. Moreover, univariate and multivariate Cox proportional hazards regression model indicated that high TP73 expression was identified as an independent factor for predicting favorable overall survival in cervical cancer patients. In conclusion, TP73 expression is increased in cervical cancer tissues and cells, and acts as a credible biomarker for predicting favorable overall survival in cervical cancer patients.

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“…Among the ten transcription regulators, we noted that the overexpression of EPAS1 was associated with poor prognosis in colorectal carcinoma, according to previous reports [ 19 – 21 ]. Polymorphism and expression of TP73 were associated with carcinogenesis and colorectal carcinoma development [ 22 , 23 ]. TEAD1 was reported to enhance the proliferation in colorectal carcinoma [ 24 ].…”

Section: Discussionmentioning

confidence: 99%

Regulatory activity based risk model identifies survival of stage II and III colorectal carcinoma

et al. 2017

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Clinical and pathological indicators are inadequate for prognosis of stage II and III colorectal carcinoma (CRC). In this study, we utilized the activity of regulatory factors, univariate Cox regression and random forest for variable selection and developed a multivariate Cox model to predict the overall survival of Stage II/III colorectal carcinoma in GSE39582 datasets (469 samples). Patients in low-risk group showed a significant longer overall survival and recurrence-free survival time than those in high-risk group. This finding was further validated in five other independent datasets (GSE14333, GSE17536, GSE17537, GSE33113, and GSE37892). Besides, associations between clinicopathological information and risk score were analyzed. A nomogram including risk score was plotted to facilitate the utilization of risk score. The risk score model is also demonstrated to be effective on predicting both overall and recurrence-free survival of chemotherapy received patients. After performing Gene Set Enrichment Analysis (GSEA) between high and low risk groups, we found that several cell-cell interaction KEGG pathways were identified. Funnel plot results showed that there was no publication bias in these datasets. In summary, by utilizing the regulatory activity in stage II and III colorectal carcinoma, the risk score successfully predicts the survival of 1021 stage II/III CRC patients in six independent datasets.

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The Prognostic Value of P73 Overexpression in Colorectal Carcinoma

Abstract: All these findings prove that p73 expression should be considered as a valuable poor prognostic marker. Our data also suggest that TP73 gene may play a role in colorectal carcinoma development.

Cited by 8 publications

References 29 publications

ΔNp73, TAp73 and Δ133p53 Extracellular Vesicle Cargo as Early Diagnosis Markers in Colorectal Cancer

ΔNp73, TAp73 and Δ133p53 Extracellular Vesicle Cargo as Early Diagnosis Markers in Colorectal Cancer

TP73 is a credible biomarker for predicting clinical progression and prognosis in cervical cancer patients

Regulatory activity based risk model identifies survival of stage II and III colorectal carcinoma

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