Construction and application of dynamic online nomogram for prognosis prediction of patients with advanced (Stage III/IV) tongue squamous cell carcinoma.

OBJECTIVES: The prognosis of patients with advanced tongue squamous cell carcinoma (ATSCC) is poor, and their overall survival (OS) is relatively short. Currently, the TNM stage system is often used clinically to assess the prognosis of patients, but the evaluation index of the TNM stage system is relatively single and does not specifically demonstrate relevant prognostic data. Therefore, the purpose of this study was to construct a dynamic online nomogram for predicting the prognosis of patients with ATSCC and to provide some reference for personalized clinical treatment of patients. METHODS: Clinical and prognostic information on patients with pathologically confirmed ATSCC from 2000 to 2018 was extracted from the SEER database and randomly divided into a training cohort and a validation cohort in a 7:3 ratio. Multifactorial and univariate Cox regression analyses were used to identify prognostic risk factors. Dynamic online nomogram were constructed using R software. Area under the curve (AUC), C-index, calibration curve, and decision curve analysis (DCA) with time-dependent ROC curves were used to assess the clinical utility of the nomogram. Kaplan-Meier survival curves were used to compare the prognosis of different patient categories. RESULTS: A total of 3828 patients with ATSCC were screened in the SEER database.Age,race, primary site, AJCC T,N and M stage, lymph nodes surgery, radiotherapy, chemotherapy and marital status were independent influences on OS(P < 0.05). In the training cohort, the C-index of the OS-related line plot was 0.733 and the AUC for predicting 3-year OS was 0.867. In the validation cohort, the C-index was 0.738 and the AUC for 3-year OS was 0.899. Calibration plots and DCA curves showed good predictive performance of the model in both the training and validation cohorts. Kaplan-Meier survival curves showed that chemotherapy, lymph nodes surgery,married,primary site(tongue base) and radiotherapy had better OS than the non-chemotherapy, non-surgery, single, primary site(tongue anterior), and non-radiotherapy groups, respectively (all P < 0.05). CONCLUSION: The established dynamic online nomogram has good predictive performance, which helps to personalize and combine the actual clinical patients to comprehensively predict the prognosis of ATSCC patients and may have better clinical application than the TNM stage system.

A nomogram for predicting survival in Patients with oral tongue keratinized squamous cell carcinoma: A SEER-based study.

OBJECTIVE: Oral tongue keratinized squamous cell carcinoma (OTKSCC), a relatively rare form of tongue cancer (TC) in clinical practice, accompanied by features of cell keratosis, is an uncommon histological subtype. However, its specific clinicopathological features and prognosis have not been adequately described. In this study, we aimed to create a nomogram using R language software to predict overall survival (OS) of patients with OTKSCC to assess the prognosis of OTKSCC patients. METHODS: We extracted clinical and related prognostic data of OTKSCC patients from 1975 to 2019 from the Surveillance, Epidemiology, and End Results database. Independent prognostic factors were selected using univariate and multivariate Cox analyses, and a nomogram was constructed using R software. The C-index, area under the curve (AUC) of receiver operating characteristic curves, calibration curves, and decision curve analysis (DCA) were used to assess the clinical utility of the nomogram. Finally, OS was assessed using the Kaplan-Meier method. RESULTS: A total of 2450 OTKSCC patients were included in the study. Univariate and multivariate Cox regression analyses were used to identify age, T stage, N stage, surgery, and radiation therapy as independent risk factors (p<0.05). In the training cohort, the calibration index of the nomogram was 0.725, while the AUC values for nomogram, age, T stage, N stage, surgery and radiation therapy were 0.878, 0.639, 0.781, 0.661, 0.724 and 0.354, respectively. At the same time, in the verification queue, the calibration index of the nomogram was 0.726, while the AUC values for nomogram, age, T stage, N stage, surgery and radiation therapy were 0.859,0.612,0.826,0.675,0.758 and 0.303, respectively. Ideal uniformity of the models from the training and validation cohorts was demonstrated in the calibration and DCA curves. Univariate survival analysis showed that age, T stage, N stage, surgery, and radiotherapy were statistically significant for prognosis (p<0.05). CONCLUSION: Age, T stage, N stage, surgery, and radiation therapy are independently associated with the OS, and the established nomogram is an effective visualization tool for predicting the OS of OTKSCC patients.

MEKK2 and MEKK3 orchestrate multiple signals to regulate Hippo pathway.

The Hippo pathway is an evolutionarily conserved signaling pathway that controls organ size in animals via the regulation of cell proliferation and apoptosis. It consists of a kinase cascade, in which MST1/2 and MAP4Ks phosphorylate and activate LATS1/2, which in turn phosphorylate and inhibit YAP/TAZ activity. A variety of signals can modulate LATS1/2 kinase activity to regulate Hippo pathway. However, the full mechanistic details of kinase-mediated regulation of Hippo pathway signaling remain elusive. Here, we report that TNF activates LATS1/2 and inhibits YAP/TAZ activity through MEKK2/3. Furthermore, MEKK2/3 act in parallel to MST1/2 and MAP4Ks to regulate LATS1/2 and YAP/TAZ in response to various signals, such as serum and actin dynamics. Mechanistically, we show that MEKK2/3 interact with LATS1/2 and YAP/TAZ and phosphorylate them. In addition, Striatin-interacting phosphatase and kinase (STRIPAK) complex associates with MEKK3 via CCM2 and CCM3 to inactivate MEKK3 kinase activity. Upstream signals of Hippo pathway trigger the dissociation of MEKK3 from STRIPAK complex to release MEKK3 activity. Our work has uncovered a previous unrecognized regulation of Hippo pathway via MEKK2/3 and provides new insights into molecular mechanisms for the interplay between Hippo-YAP and NF-κB signaling and the pathogenesis of cerebral cavernous malformations.