BackgroundPrimary pulmonary mucoepidermoid carcinoma (PMEC) is an extremely rare malignancy. Its clinical characteristics and prognosis are not fully understood. This study evaluated clinical characteristics and prognostic factors of PMEC and established a nomogram to predict its 1-, 3-, 5- and 10-year cancer-specific survival (CSS) rates.MethodsIn the Surveillance, Epidemiology, and End Results database from January 1, 2016 to December 31, 2016, patients pathologically diagnosed with PMEC were identified. Kaplan–Meier analysis and Cox regression were performed to evaluate the CSS stratified by different covariates. A predictive nomogram model was built and validated by the concordance index (C-index) and calibration curves.ResultsA total of 585 PMEC patients were identified. A total of 408 (70%) of patients were placed into the training cohort, and 177 (30%) patients were placed into the validation cohort. The 5- and 10-year CSS rates of stage I–II PMEC patients were 91.4 and 88.9, respectively. The 1-, 3- and 5-year CSS rates of stage III–IV PMEC were 56.5, 39.45, and 32.1%, respectively. Survival curves showed that older age, large tumor size, poor differentiation, and high TNM stage were associated with a significantly worse prognosis. CSS outcomes were significantly better in patients who received surgical treatments (surgical alone, surgery plus radiation and/or chemotherapy). Patients who received radiation and/or chemotherapy had the worst prognosis. Multivariate Cox results revealed that covariates, including age, tumor laterality, tumor sizes, pathological differentiation, lymph node metastasis, distant metastasis, TNM stage and therapy, were independent prognostic factors for PMEC. These factors were used to construct a nomogram. The C-index of the nomogram was 0.921. The calibration curve presented favorable consistency between the predicted CSS and actual observations. This nomogram was validated by the validation cohort. The C-index of the validation cohort was 0.968.ConclusionAge, bilateral tumors, tumor size, pathological differentiation grade, lymph node metastasis, distant metastasis, TNM stage and therapy were independent prognostic factors of PMEC patients. The first nomogram for predicting the CSS of PMEC was built and validated, showing its potential value in practice.

Objective: To evaluate the survival difference of radical prostatectomy (RP) and external beam radiotherapy (EBRT) in elderly men (75 years and older) with high-risk (HR) or very high-risk (VHR) prostate cancer (PCa). Methods: Elderly men diagnosed with HR/VHR PCa from 2004-2015 in the Surveillance, Epidemiology and End Results (SEER) database were identified. Propensity-score matching (PSM) was conducted to balance the covariates; Kaplan-Meier and Cox analysis were performed to evaluate the overall survival (OS) and prostate cancer-specific survival (PCSS). Results: 11698 patients with HR PCa and 4415 patients with VHR PCa were identified and divided into RP and EBRT group. After PSM, 964 patients with HR PCa and 538 patients with VHR PCa were included in each group. The 10-year OS and PCSS of men with HR PCa were 60.1% vs 40.9% and 90.6% vs 83.4%, respectively. The 10-year rate of OS and PCSS in men with VHR PCa were 55.9% vs 33.3% and 82.4% vs 75.6%, respectively. The OS curve of patients with HR PCa revealed that RP was significantly better than EBRT in both overall cohort [HR: 0.533, 95%CI (0.485~0.586), p<0.001] and the matched cohort [HR: 0.703, 95%CI (0.595~0.832), p<0.001]. However, the PCSS curve of patients with HR PCa showed that RP was significantly better than EBRT in overall cohort [HR: 0.453, 95%CI (0.368~0.559), p<0.001] but was similar to EBRT in matched cohort [HR: 0.820, 95%CI (0.552~1.218), p=0.327]. As for patients with VHR PCa, RP was associated with better OS than EBRT whether in overall cohort [HR: 0.520, 95%CI (0.457~0.592), p<0.001] or matched cohort [0.695, 95%CI (0.551~0.876), p=0.002]. The PCSS of RP was significantly better than that of EBRT in overall cohort [HR: 0.538, 95%CI (0.422~ 0.685), p<0.001], but was similar in matched cohort [HR: 0.787, 95%CI (0.510 ~1.214), p=0.281]. Conclusions: RP has more survival benefits than EBRT in men aged 75 years and older with HR or VHR PCa.

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<b><i>Objective:</i></b> The aim of this study was to evaluate the survival outcomes of radical prostatectomy (RP), external beam radiotherapy plus brachytherapy (EBRT + BT), and EBRT alone among elderly men (aged 70 years and above) with very high-risk (VHR) prostate cancer (PCa). <b><i>Methods:</i></b> We identified elderly men diagnosed with VHR PCa between 2004 and 2015 in the Surveillance, Epidemiology, and End Results database. The propensity score-matching method was adopted to balance the covariates and generate new cohorts. ­Kaplan-Meier and Cox analyses were conducted to build up survival curves and evaluate the overall survival (OS) and PCa-specific survival (PCSS) outcomes. <b><i>Results:</i></b> A total of 9,818 patients were identified. Of them, 5,839 were in the EBRT group, 725 in the EBRT + BT group, and 3,254 in the RP group. The survival curves of the overall cohort showed that RP was associated with the best OS, followed by EBRT + BT and EBRT (<i>p</i> &#x3c; 0.001). As for the PCSS, RP shared similar outcomes with EBRT + BT (hazard ratio [HR]: 1.25 [0.93–1.69], <i>p</i> = 0.175). EBRT was associated with significantly worse PCSS than both RP (HR: 1.88, 95% confidence interval [95% CI] [1.64–2.15], <i>p</i> &#x3c; 0.001) and EBRT + BT (HR: 1.48, 95% CI [1.19–1.85], <i>p</i> = 0.002). In the matched cohorts, RP presented better OS (HR: 1.41, 95% CI [1.07–1.86], <i>p</i> = 0.041) and similar PCSS with EBRT + BT (HR: 1.50, 95% CI [0.91–2.47], <i>p</i> = 0.12). RP was associated with significantly better OS and PCSS outcomes than EBRT alone (OS HR: 1.58, 95% CI [1.59–2.12], <i>p</i> &#x3c; 0.001; PCSS HR: 2.08 [1.60–2.72], <i>p</i> &#x3c; 0.001). EBRT + BT also had significantly better OS and PCSS outcomes than EBRT alone (OS HR: 1.33, 95% CI [1.11–1.60], <i>p</i> &#x3c; 0.001; PCSS HR: 1.57 [1.13–2.19], <i>p</i> = 0.003). <b><i>Conclusions:</i></b> For patients above 70 years with VHR PCa, RP was associated with better OS and similar PCSS than EBRT + BT. Both RP and EBRT + BT have better OS and PCSS than EBRT alone.

Objective: The aim of this study was to evaluate the prognosis of patients with metastatic prostate cancer (mPCa) in different age groups. Methods: Patients with mPCa from 2004 to 2016 in the Surveillance, Epidemiology and End Results (SEER) database were identified. Seven groups were divided according to the age at diagnosis, including ≤55 years, 56-60 years, 61-65 years, 66-70 years, 71-75 years, 76-80 years and >80 years. Fine and Gray's competing risks model and Kaplan-Meier analysis were conducted to evaluate the cancer-specific survival (CSS). Results: A total of 36231 patients with mPCa were included. The CSS curves of the overall cohort showed that patients aged ≤55 years had significantly worse CSS than patients in age groups of 56-60 [HR:0.93 (0.87~1.00), p=0.039], 61-65 [HR:0.91 (0.85~0.97), p=0.003] and 66-70 [HR:0.90 (0.84~0.96), p=0.001]. After removing patients dead for other reasons, the differences of CSS curves between ≤55 years group and 56-70 years groups were not significant. However, the mean survival time of ≤55 years group (55.78±2.48 months) was still shorter than 56-60 years (57.28±2.35 months), 61-65 years (57.64±2.07 months), and 66-70 years (57.11±2.11 months). When stratified by M stages, similar results were found in M1a, M1b and M1c stage groups. According to Fine-Gray competing risks models, patient ≤55 years featured significantly higher sub-distribution hazard ratio (sdHR) than 61-65 years group [sdHR: 0.94(0.88~1.00); p=0.046]. Conclusions:The mPCa patients ≤55 years seemed to be associated with worse prognosis in comparison with patients aging 56-70 years.

Background: The aim was to evaluate the prognosis of men with all possible high-risk prostate cancers (PCa) stratified by risk factors.Methods: Within the Surveillance, Epidemiology and End Results (SEER) database from 2004 to 2015, men with non-metastasis high-risk PCa were identified. Kaplan-Meier analysis and Cox regressions were adopted to evaluate the overall survival (OS) and prostate cancer-specific survival (PCSS). Nomograms were conducted to build a predictive model. Concordance index (C-index) and calibration curves were used to validate the model.Results: A total of 151,799 patients were included. Seven risk groups were divided including one highrisk factor of T3-4 (A1), prostate-specific antigen (PSA) >20 ng/mL (A2), and Gleason score (GS) 8-10, two high-risk factors of T3-4 PSA >20 ng/mL (B1), T3-4 GS 8-10 (B2), PSA >20 ng/mL GS 8-10 (B3), and three high-risk factors of T3-4 PSA >20 ng/mL GS 8-10 (C). The survival curves of PCSS showed that A1 was the best among all groups. A2, A3 and B1 had similar results and were all better than B2 [with A2 as

Accumulating evidence indicates that the lysosomal Ragulator complex is essential for the full activation of the mechanistic target of rapamycin complex 1 (mTORC1). Abnormal mTORC1 activation has been implicated in cancer and glycolytic metabolism associated with drug resistance. Fasting is known to upregulate the ring finger protein 152 (RNF152) and mediate the metabolic status of cells. Here we report that RNF152 regulates mTORC1 signaling by targeting p18, a subunit of the Ragulator, and attenuates gemcitabine resistance in gallbladder cancer (GBC). The effects of RNF152 expression on molecular behavior were analyzed. RNF152 and p18 levels were detected in tissues, and detailed mechanistic studies were undertaken by using activators, inhibitors, and lentivirus transfections. RNF152 levels were significantly lower in GBC than in adjacent non-cancer tissues. Fasting impairs glycolysis, induces gemcitabine sensitivity, and upregulates the expression of RNF152. RNF152 overexpression increases the sensitivity of GBC cells to the chemotherapeutic drug gemcitabine, whereas silencing RNF152 exhibited the opposite effect. Our study verified that fasting-induced RNF152 ubiquitinates p18, resulting in proteasomal degradation. RNF152 deficiency induces the increased lysosomal localization of p18 and other members of the Ragulator-Rag complex, and increased mTORC1 activity, to promote glycolysis and decrease gemcitabine sensitivity in GBC. Our research suggests that RNF152 is a fasting sensor and an important regulator of the mTORC1 signal. RNF152 functions as a tumor suppressor that can suppress the activity of mTORC1 to inhibit glycolysis and enhance the sensitivity of gemcitabine in GBC. RNF152 may have potential in the therapeutic management of GBC.

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