Background TP53 is one of the most frequently mutated genes among all cancer types, and TP53 mutants occur more than 60% in colorectal cancer (CRC). Among all mutants, there are three hot spots, including p53-R175H, p53-R248W and p53-R273H. Emerging evidence attributes cancer carcinogenesis to cancer stem cells (CSCs). Long noncoding RNAs (lncRNAs) play crucial roles in maintaining the stemness of CSCs. However, it is unknown if mutant p53-regulated lncRNAs are implicated in the maintenance of CSC stemness. Methods RNA-sequencing (RNA-seq) and ChIP-sequencing (ChIP-seq) were used to trace the lncRNA network regulated by p53-R273H in HCT116 endogenous p53 point mutant spheroid cells generated by the somatic cell knock-in method. RT-qPCR was used to detect lncRNA expression patterns, verifying the bioinformatics analysis. Transwell, spheroid formation, fluorescence activated cell sorter (FACS), xenograft nude mouse model, tumor frequency assessed by extreme limiting dilution analysis (ELDA), Western blot assays and chemoresistance analysis were performed to elucidate the functions and possible mechanism of lnc273–31 and lnc273–34 in cancer stem cells. Results p53-R273H exhibited more characteristics of CSC than p53-R175H and p53-R248W. RNA-seq profiling identified 37 up regulated and 4 down regulated differentially expressed lncRNAs regulated by p53-R273H. Combined with ChIP-seq profiling, we further verified two lncRNAs, named as lnc273–31 and lnc273–34, were essential in the maintenance of CSC stemness. Further investigation illustrated that lnc273–31 or lnc273–34 depletion dramatically diminished colorectal cancer migration, invasion, cancer stem cell self-renewal and chemoresistance in vitro. Moreover, the absence of lnc273–31 or lnc273–34 dramatically delayed cancer initiation and tumorigenic cell frequency in vivo. Also, lnc273–31 and lnc273–34 have an impact on epithelial-to mesenchymal transition (EMT). Finally, lnc273–31 and lnc273–34 were significantly highly expressed in CRC tissues with p53-R273H mutation compared to those with wildtype p53. Conclusions The present study unveiled a high-confidence set of lncRNAs regulated by p53-R273H specific in colorectal CSCs. Furthermore, we demonstrated that two of them, lnc273–31 and lnc273–34, were required for colorectal CSC self-renewal, tumor propagation and chemoresistance. Also, the expression of these two lncRNAs augmented in colorectal cancer patient samples with p53-R273H mutation. These two lncRNAs may serve as promising predictors for patients with p53-R273H mutation and are vital for chemotherapy. Electronic supplementary material The online version of this article (10.1186/s13046-019-1375-9) contains supplementary material, which is available to authorized users.

Background Lymph node dissection (LND) is of great significance in intrahepatic cholangiocarcinoma (ICC). Although the National Comprehensive Cancer Network (NCCN) guidelines recommend routine LND in ICC, the effects of LND remains controversial. This study aimed to explore the role of LND and some related issues and of in ICC. Methods Patients were identified in two Chinese academic centers. Inverse probability of treatment weighting (IPTW) was used to reduce bias. Kaplan–Meier curves and Cox proportional hazards models were used to compare overall survival (OS) and disease-free survival (DFS). Results Of 232 patients, 177 (76.3%) underwent LND, and 71 (40.1%) had metastatic lymph nodes. A minimum of 6 lymph nodes were dissected in 66 patients (37.3%). LND did not improve the prognosis of ICC. LNM > 3 may have worse OS and DFS than LNM 1–3, especially in the LND >  = 6 group. For patients who did not underwent LND, the adjuvant treatment group had better OS and DFS. Conclusions The proportions of patients who underwent LND and removed >  = 6 lymph nodes were not high enough. LND has no definite predictive effect on prognosis. Patients with 4 or more LNMs may have a worse prognosis than patients with 1–3 LNMs. Adjuvant therapy may benefit patients of nLND.

Background Although the National Comprehensive Cancer Network guidelines recommend routine lymph node dissection (LND) in intrahepatic cholangiocarcinoma (ICC), the role of LND remains controversial, and the node (N) stage is oversimplified. Methods Patients were identified from the Surveillance, Epidemiology, and End Results research data 18 (SEER 18). Propensity score matching (PSM) was used to reduce bias, and Kaplan–Meier curves and Cox proportional hazards models were used to compare overall survival (OS). The best cutoff values were found using X-tile software. Results Of 2037 patients included in SEER 18, 1147 underwent LND (56.3%); 389 (34.3%) had pathologically confirmed lymph node metastasis (LNM), and 316 (27.6%) had at least 6 LNDs. The median OS was worse for LND patients (34 months vs. 40 months, respectively), and this result remained after PSM. Male sex, age ≥60 years, tumor size > 5 cm, and LNM were independent prognostic risk factors for ICC. LNM ≥3 was associated with worse OS. Conclusions Only a few LNDs met the requirements per the guidelines. LND does not improve OS in ICC, and the best approach to LND and a better N staging method should be explored further.

Background Colorectal cancer (CRC) is one of the most common malignancies, and it’s expected that the CRC burden will substantially increase in the next two decades. New biomarkers for targeted treatment and associated molecular mechanism of tumorigenesis remain to be explored. In this study, we investigated whether PDCD6 plays an oncogenic role in colorectal cancer and its underlying mechanism. Methods Programmed cell death protein 6 (PDCD6) expression in CRC samples were analyzed by immunohistochemistry and immunofluorescence. The prognosis between PDCD6 and clinical features were analyzed. The roles of PDCD6 in cellular proliferation and tumor growth were measured by using CCK8, colony formation, and tumor xenograft in nude mice. RNA-sequence (RNA-seq), Mass Spectrum (MS), Co-Immunoprecipitation (Co-IP) and Western blot were utilized to investigate the mechanism of tumor progression. Immunohistochemistry (IHC) and quantitative real-time PCR (qRT-PCR) were performed to determine the correlation of PDCD6 and MAPK pathway. Results Higher expression levels of PDCD6 in tumor tissues were associated with a poorer prognosis in patients with CRC. Furthermore, PDCD6 increased cell proliferation in vitro and tumor growth in vivo. Mechanistically, RNA-seq showed that PDCD6 could affect the activation of the MAPK signaling pathway. PDCD6 interacted with c-Raf, resulting in the activation of downstream c-Raf/MEK/ERK pathway and the upregulation of core cell proliferation genes such as MYC and JUN. Conclusions These findings reveal the oncogenic effect of PDCD6 in CRC by activating c-Raf/MEK/ERK pathway and indicate that PDCD6 might be a potential prognostic indicator and therapeutic target for patients with colorectal cancer.

The objective for the study was to analysis the epidemiology of adenosarcoma, and independent prognostic factors and impact of lymph node dissection (LND) of uterine adenosarcoma. Cases of patients with primary adenosarcoma were obtained from the Surveillance, Epidemiology, and End Results (SEER) database from 2000 to 2016. Overall survival was analyzed by the Kaplan-Meier method and log-rank test. The differences in baseline covariates between the 2 groups were adjusted by inverse probability of treatment weighting method. The prognostic factors were identified by univariate and multivariate Cox regression analysis and hazard ratio and 95% confidence interval (CI) of covariates were also estimated. 1129 patients with pathological primary adenosarcoma between 2000 and 2016 were identified from the surveillance, epidemiology, and end results database. The only 4 patients were male. 1027 patients with primary uterine adenosarcoma, and 53.1% underwent LND and only 3.5% patients were with positive lymph node. Age, marital status, largest tumor size, tumor grade, T stage and chemotherapy were significantly correlated with survival. Race, tumor number, LND, and radiotherapy did not affect overall survival in patients. Inverse probability of treatment weighting-adjusted K-M curve showed that LND did not improve survival and lymph node metastasis (LNM) did not affect survival. The majority of primary adenosarcoma patients are female with high incidence of uterus and rare incidence of distant metastasis. Age, marital status, tumor size, T stage, grade, and chemotherapy are independent prognostic factors of uterine adenosarcoma. LNM was not a significant prognostic risk factor, and LND did not benefit survival.

<b><i>Introduction:</i></b> Although gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) with liver metastasis encompass a wide variety of clinical conditions with various prognosis, no statistical model for predicting the prognosis of these patients has been established. We sought to establish a more elaborative and individualized nomogram to predict survival of patients with liver-limited metastatic GEP-NENs. In addition, this nomogram was validated by both the Surveillance, Epidemiology, and End Results (SEER) database and a Chinese multicenter cohort. <b><i>Methods:</i></b> Patients diagnosed with GEP-NENs with liver-limited metastasis between 2010 and 2016 were identified from the SEER database. Kaplan-Meier survival analysis was performed to analyze survival outcomes. A nomogram was established based on the independent prognostic variables identified from univariate and multivariate Cox regression analyses. The nomogram was evaluated in both an internal validation SEER dataset and an external validation dataset composed of patients from the Chinese multicenter cohort. <b><i>Results:</i></b> A total of 1,474 patients from the SEER database and 192 patients from the multicenter cohort were included. Age, tumor size, differentiation, primary tumor resection, and liver metastasis resection were identified as independent prognostic factors by univariate and multivariate Cox analyses and were verified by Kaplan-Meier survival analysis (all <i>p</i> &#x3c; 0.0001). A nomogram was developed and validated by calibration curves and areas under the curve of the external validation cohort, which showed good consistency and veracity in predicting overall survival. <b><i>Conclusion:</i></b> A nomogram was developed for the first time to predict the survival of patients with liver-limited metastases from GEP-NENs. Both internal and external validation demonstrated excellent discrimination and calibration of our nomogram. Based on this prognostic model, clinicians could develop more personalized treatment strategies and surveillance protocols.

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Adenosarcoma is a rare type of tumor with a mixture of epithelial and stromal components and often occurs in the female reproductive system. Primary hepatic adenosarcoma (PHAS) is extremely rare, with only two cases reported so far. Both patients had poor outcomes. Here, we report the case of a 36-year-old man with pain under the xiphoid process who was diagnosed with a bile duct tumor. He was treated with adjuvant radiotherapy when surgery was performed on him. Pathologically, the tumor contained benign epithelial tissue, and the submucosa of the bile duct in the liver showed infiltrating growth of spindle cell components. The cells were dense, mildly heterotypic, and occasionally mitotic, and the patient was diagnosed with PHAS. Whole-exome sequencing results showed that a total of 12 mutations were shared by the two tissues. The patient received adjuvant radiotherapy and he was tumor-free until 31 months postoperatively. This case will provide some references of the disease to other researchers.