The Selection of Treatment Modality for Breast Ductal Carcinoma In Situ: Experience From a Single Institution.

PURPOSE: Although breast conservation surgery(BCS) followed by adjuvant radiotherapy is now the mainstream treatment method for breast ductal carcinoma in situ(DCIS), mastectomy is still performed in some patients who refuse to undergo radiation. However, the most effective treatment method for these patients is still unknown. In the current study, we aimed to compare the survival rates between mastectomy and BCS plus adjuvant radiotherapy in patients with DCIS. MATERIALS AND METHODS: We performed a retrospective study of 333 patients with DCIS from May 2004 to December 2016. There were 209 patents who were treated with BCS and adjuvant radiotherapy, while the remaining of 124 patients underwent mastectomy. The disease-free survival (DFS) and local recurrence-free survival(LRFS) rates were compared between the 2 treatment groups. Cox proportional hazards regression was performed to explore factors associated with DFS and LRFS. RESULTS: The 10-year local recurrence(LR) rates in the mastectomy and BCS plus adjuvant radiotherapy groups were 2.6% and 7.5%, respectively. There was no difference in the LR rate between the 2 groups. Furthermore the DFS rate was also similar between the mastectomy and BCS plus adjuvant radiotherapy groups. Based on the multivariable analysis, age and tumor grade were significantly correlated with the LRFS and DFS rates. In the subgroup analysis based on the factors of age and tumor grade, patients with a tumor grade of III who underwent mastectomy had better LRFS and DFS rates compared to those who received BCS plus radiotherapy. CONCLUSION: In patients with DCIS, the long-term efficacy was similar between mastectomy and BCS followed by adjuvant radiotherapy. However, in the subgroup of patients with grade III tumors, mastectomy seems to offer a better LRFS and DFS than BCS plus radiotherapy.

Clinical characteristics and prognosis of anal squamous cell carcinoma: a retrospective audit of 144 patients from 11 cancer hospitals in southern China.

BACKGROUND: The incidence of anal squamous cell carcinoma (SCC) has been steadily growing globally in the past decade. Clinical data on anal SCC from China are rare. We conducted this study to describe the clinical and epidemiological characteristics of anal SCC in China and explore prognostic factors of outcomes among patients with anal SCC. METHODS: We audited demographic characteristics, relevant symptoms, risk factors, treatment modalities and outcomes for patients diagnosed with anal SCC at 11 medical institutions in China between January 2007 and July 2018. RESULTS: A total of 144 patients (109 females) were diagnosed with SCC during this period. Median age at initial diagnosis was 52.0 (interquartile range: 46.0-61.8) years. The most common symptoms were bleeding (n = 93, 64.6%), noticing a lump (n = 49, 34.0%), and pain (n = 47, 32.6%). The proportion of patients at the American Joint Committee on Cancer (AJCC) stages I-IV were 10 (6.9%), 22 (15.3%), 61 (42.4%) and 8 (5.6%), respectively, and AJCC stages in 43 (29.9%) patients were unknown. Thirty-six patients (25.0%) underwent abdominoperineal resection initially. Univariable analysis showed that T stage predicted recurrence-free survival (RFS) (Hazard ratio [HR] = 3.03, 95% Confidence interval [CI]: 1.10-8.37, p = 0.032), and age group (HR = 2.90, 95% CI: 1.12-7.49, p = 0.028), AJCC stage (HR = 4.56, 95% CI: 1.02-20.35, p = 0.046), and N stage (HR = 3.05, 95% CI: 1.07-8.74, p = 0.038) predicted overall survival (OS). CONCLUSIONS: T stage was identified as prognostic factor of RFS, and age, AJCC stage, and N stage were identified as prognostic factors of OS. Improving symptom awareness and earlier presentation among patients potentially at risk for anal SCC should be encouraged. Familiarity with the standard treatment among health care providers in China should be further improved.

The Selection of Time Interval Between Surgery and Adjuvant Therapy in Early Stage Cervical Cancer.

OBJECTIVES: The optimal interval between surgery and adjuvant treatment has not yet been found in cervical cancer. And whether patients with different FIGO stage should choose different interval is unknown. The purpose of this study was to evaluate whether interval has a different effect on oncologic outcome for patients with different tumor stages. METHODS: We performed a retrospective study of 226 cervical cancer patients who were treated by surgery and adjuvant therapy from May 2005 to August 2015. All patients were divided into 2 groups according to the interval of 5 weeks. Overall survival (OS) and disease-free survival (DFS) were compared between patients with interval shorter and longer than 5 weeks in the whole group and subgroups. Recurrence patterns were also analyzed. Multivariate analysis was performed to explore clinical factors significantly associated with DFS, local recurrence-free survival and distant metastasis-free survival for patients with stage IB2-IIA. RESULTS: For patients with stage IA2-IB1, the 5-year OS and DFS were similar between groups of short and long interval with also the comparable results of local and distant failure. For patients with IB2-IIA, both the OS and DFS in the short-interval group were higher than that in the long-interval group. Besides, the rates of local recurrence were found higher in the group of long interval compared with short interval. Multivariable analysis indicated that time interval was an independent predictor of DFS and local recurrence-free survival for patients with stage IB2-IIA. CONCLUSIONS: In cervical cancer patients, time interval between surgery and adjuvant therapy may have different effects on the prognosis in different FIGO stages.

Micro-invasive surgery combined with intraoperative radiotherapy for the treatment of spinal metastasis.

PURPOSE: This is a retrospective analysis of the strategy and clinical results of surgery combined with intraoperative radiotherapy (IORT) to treat spinal metastases. METHODS: We delivered tumour-conformal IORT in 40 patients with 52 metastatic vertebrae based on our surgical classification system. The strategies were evaluated with respect to neurologic function and spinal stability. The EORTC QLQ-BM22, visual analogue scale (VAS) and the Frankel Scale were used to assess quality of life, pain and neurologic function. Local control was evaluated every 3 months using X-rays and MRI. RESULTS: Micro-invasive IORT was performed in 42 vertebrae (80.8%), and open surgery with IORT was performed in 10 vertebrae (19.2%). Single-level, 2-level and 3-level IORT was performed in 30, 8 and 2 cases, respectively. The delivered dose was 9.2 ± 3.6 Gy (8-15 Gy) with a depth of 10.1 ± 2.1 mm. The actual IORT treatment time was 5 min and 16 s. The follow-up period was 6-23 months (mean: 12.5 months). The local control rate was 92.3%. The EORTC QLQ-BM22 scores showed that patients had significant improvements in pain location, degree and function after treatment (P < 0.01). Thirty-five patients (89.7%) achieved pain relief throughout the follow-up period. VAS scores were significantly reduced by 3.4 points 3 months after treatment. Neurological function was improved in 7 patients (87.5%). No radiation-related complications were observed. CONCLUSIONS: Surgery combined with tumour-conformal IORT can effectively relieve pain, achieve good local control and improve QOL.

The long non-coding RNA HOTAIR affects the radiosensitivity of pancreatic ductal adenocarcinoma by regulating the expression of Wnt inhibitory factor 1.

Pancreatic ductal adenocarcinoma (PDAC) is seriously resistant to radiotherapy and the mechanism is largely unknown. HOX transcript antisense intergenic RNA (HOTAIR) is overexpressed in PDAC. However, the function of HOTAIR has never been related to the radiosensitivity of PDAC. In this present study, the expression of HOTAIR in the PDAC cell lines and tissues was measured by quantitative real-time PCR (qRT-PCR), and the association between HOTAIR expression levels and X-ray treatment in PDAC cell lines was investigated. Additionally, the influence of HOTAIR knockdown on radiosensitivity, proliferation, and apoptosis of PDAC cells after radiation was evaluated by colony formation assays, Cell Counting Kit-8 (CCK-8) assays, and flow cytometry, respectively. Furthermore, the correlation between HOTAIR and Wnt inhibitory factor 1 (WIF-1) expression in PDAC cell lines and tissues was studied to assess the role of HOTAIR and WIF-1 in the radiosensitivity of PDAC. The results confirmed that HOTAIR expression was significantly increased in the PDAC cell lines and tissues (n = 90) compared with human normal pancreatic ductal epithelial cell line (HPDE) and matched adjacent normal tissues (n = 90). Functionally, HOTAIR knockdown enhanced the radiosensitivity of PDAC cells, reduced the proliferation, and increased the apoptosis of cells after radiation. And HOTAIR silencing increased the expression of WIF-1. Furthermore, the overexpression of WIF-1 revealed that HOTAIR modulated the radiosensitivity of PDAC cells by regulating the expression of WIF-1. These data reveals that HOTAIR can affect the radiosensitivity of PDAC cells partly via regulating the expression of WIF-1, and HOTAIR-WIF-1 axis is a potential target for PDAC radiotherapy.

The prognostic impact of preoperative blood monocyte count in pathological T3N0M0 rectal cancer without neoadjuvant chemoradiotherapy.

It remains controversial whether adjuvant therapy should be delivered to pathological T3N0M0 rectal cancer without neoadjuvant chemoradiotherapy. Thus identification of patients at high risk is of particular importance. Herein, we aimed to evaluate whether the absolute peripheral blood monocyte count can stratify the pathological T3N0M0M0 rectal cancer patients in survival. A total of 270 pathological T3N0M0 rectal cancer patients with total mesorectal excision-principle radical resection were included. The optimal cut-off value of preoperative monocyte count was determined by receiver operating characteristic curve analysis. Overall survival and disease-free survival between low- and high-monocyte were estimated by Kaplan-Meier method and Cox regression model. The optimal cut-off value for monocyte count was 595 mm(3). In univariate analysis, patients with monocyte counts higher than 595/mm(3) had significantly inferior 5-year overall survival (79.2 vs 94.2 %, P = 0.006) and disease-free survival (67.8 vs 86.0 %, P < 0.001). With adjustment for the known covariates, monocyte count remained to be associated with poor overall survival (HR = 2.55, 95 % CI 1.27-5.10; P = 0.008) and disease-free survival (HR = 2.63, 95 % CI 1.48-4.69; P = 0.001). Additionally, the significant association of monocyte count with disease-free survival was hardly influenced in the subgroup analysis, whereas this correlation was restricted to the males and patients with normal carcinoembryonic antigen (CEA) level (<5 µg/L), tumor grade II, and with adjuvant therapy. High preoperative monocyte count is independently predictive of worse survival of pathological T3N0M0 rectal cancer patients without neoadjuvant chemoradiotherapy. Postoperative adjuvant therapy might be considered for patients with high-monocyte count.

Selective use of adjuvant chemotherapy for rectal cancer patients with ypN0.

BACKGROUND: The administration of adjuvant chemotherapy for rectal cancer patients with ypN0 is controversial. The purposes of this study were to evaluate the role of adjuvant chemotherapy in ypN0 patients and to optimize its use for these patients. METHODS: We performed a retrospective study of 160 rectal cancer patients who had the final pathology of ypN0 between March 2003 and November 2010. Overall survival (OS), disease-free survival (DFS), local recurrence-free survival (LRFS), and distant metastasis-free survival (DMFS) were compared between patients who did and did not receive adjuvant chemotherapy. Multivariate analysis was performed to explore clinical factors significantly associated with DFS, LRFS, and DMFS. RESULTS: For ypT0-2N0 patients, the 5-year OS, DFS, LRFS, and DMFS were similar between patients who did and did not receive adjuvant chemotherapy (P > 0.05). For patients with ypT3-4N0, those who were given adjuvant chemotherapy exhibited a higher 5-year OS than those who were not (P = 0.026), with also an extended 5-year DFS (P = 0.050). Further analysis indicated that adjuvant chemotherapy could decrease the rates of distant metastases for ypT3-4N0 patients with no impact on local control. In multivariable analysis, both the final pathological stage and adjuvant chemotherapy were independent predictors of DMFS for the whole group. When stratified by pathological stage, adjuvant chemotherapy was still significantly associated with DMFS in the ypT3-4 stratum. CONCLUSIONS: Adjuvant chemotherapy may not improve survival for ypT0-2N0 patients. However, it may be clinically meaningful for ypT3-4N0 patients by decreasing rates of distant metastases. Further randomized controlled clinical trials are needed to address this problem.

[Value of postoperative adjuvant chemotherapy in locally advanced rectal cancer patients with ypT1-4N0 after neo-adjuvant chemoradiotherapy].

OBJECTIVE: The purpose of this study was to investigate the value of postoperative chemotherapy for locally advanced rectal cancer patients who reached pathological ypT1-4N0 after neo-adjuvant chemoradiotherapy. METHODS: We performed a retrospective study of 104 patients treated with preoperative chemoradiotherapy followed by radical resection, who achieved pathological ypT1-4N0, between Mar 2003 and Dec 2010. There were 73 patients who received postoperative adjuvant chemotherapy, and the other 31 patients did not. The distribution of final pathologic stages for these patients was ypT1-2N0 in 39 cases and ypT3-4N0 in 65 cases. RESULTS: The median follow-up was 41 months. The 3-year overall survival rate (OS) and recurrence-free survival rate (RFS) for the whole group (ypT1-4N0) were 93.4% and 85.3%, respectively. The 3-year OS and RFS in the adjuvant chemotherapy group and non-adjuvant chemotherapy group were 95.5%, 88.6% and 88.6%, 77.2%, respectively. There were no significant differences in 3-year RFS (P = 0.108) and OS (P = 0.106) between the two groups. The 3-year local recurrence and distant metastasis rates in the adjuvant chemotherapy group were 4.1% (3/73) and 5.5% (4/73), while for the non-adjuvant chemotherapy group, the 3-year local recurrence rate and distant metastasis rate were 3.2% (1/31) and 16.1% (5/31), respectively. Significant difference was found in distant metastasis rates (P = 0.030) between the two groups, but not in local recurrence rates (P = 0.676).Further subgroup analysis indicated that for the ypT1-2N0 patients, there were no significant differences in 3-year OS (P = 0.296) and RFS (P = 0.939) between the adjuvant and non-adjuvant chemotherapy groups, while negative results displayed in 3-year local recurrence rates (P = 0.676) and distant metastasis rates (P = 0.414). However, for patients with ypT3-4N0, significant differences were showed in both the 3-year OS (P = 0.034) and RFS (P = 0.025), and further analysis revealed that the 3-year distant metastasis rate was significantly higher in the non-adjuvant chemotherapy group than in the adjuvant chemotherapy group (P = 0.010) , but with non-significant difference in the 3-year local recurrence (P = 0.548). CONCLUSIONS: Adjuvant chemotherapy may not improve survival for ypT1-2N0 patients. However, it may be clinically meaningful for ypT3-4N0 patients by decreasing distant metastasis rate. Further randomized controlled clinical trials are needed to confirm our results.

H3K27 acetylation activated long noncoding RNA RP11-162G10.5 promotes breast cancer progression via the YBX1/GLO1 axis.

PURPOSE: Long noncoding RNAs (lncRNAs) orchestrate critical roles in human tumorigenesis. However, the regulatory mechanism of lncRNAs in tissue-specific expressions in breast cancer (BC) remains poorly understood. This study aims to investigate lncRNA role and mechanisms in BC. METHODS: RNA sequencing was used to explore differentially expressed lncRNAs in BC and adjacent tissues. H3K27 acetylation (H3K27ac) chromatin immune-precipitation sequencing (ChIP-seq) data of BC cells from the GEO dataset (GSE85158) was retrieved to identify the H3K27ac activated lncRNAs that were involved in tumorigenesis. RP11-162G10.5 was selected as the target lncRNA for further functional and mechanism study. RESULTS: In this study, we identified a novel lncRNA RP11-162G10.5, whose overexpression was specifically driven by H3K27ac in luminal breast cancer. And increased RP11-162G10.5 in BC is correlated with poor patient outcomes. RP11-162G10.5 promotes tumor cell proliferation in vitro and in vivo. Mechanistically, RP11-162G10.5 recruits transcriptional factor YBX1 to the GLO1 promoter, consequently activating GLO1 transcription to modulate the progression of BC. CONCLUSIONS: Our findings suggest that the histone modification-activated lncRNA contributes to the oncogenesis of BC. Also, our data reveal a role for RP11-162G10.5 in BC tumorigenesis and may supply a strategy for targeting the RP11-162G10.5 as a potential biomarker and a therapeutic target for breast cancer patients.

Deep learning-based precise prediction and early detection of radiation-induced temporal lobe injury for nasopharyngeal carcinoma.

Background: Radiotherapy is the mainstay of treatment for nasopharyngeal carcinoma. Radiation-induced temporal lobe injury (TLI) can regress or resolve in the early phase, but it is irreversible at a later stage. However, no study has proposed a risk-based follow-up schedule for its early detection. Planning evaluation is difficult when dose-volume histogram (DVH) parameters are similar and optimization is terminated. Methods: This multicenter retrospective study included 6065 patients between 2014 and 2018. A 3D ResNet-based deep learning model was developed in training and validation cohorts and independently tested using concordance index in internal and external test cohorts. Accordingly, the patients were stratified into risk groups, and the model-predicted risks were used to develop risk-based follow-up schedules. The schedule was compared with the Radiation Therapy Oncology Group (RTOG) recommendation (every 3 months during the first 2 years and every 6 months in 3-5 years). Additionally, the model was used to evaluate plans with similar DVH parameters. Findings: Our model achieved concordance indexes of 0.831, 0.818, and 0.804, respectively, which outperformed conventional prediction models (all P < 0.001). The temporal lobes in all the cohorts were stratified into three groups with discrepant TLI-free survival. Personalized follow-up schedules developed for each risk group could detect TLI 1.9 months earlier than the RTOG recommendation. According to a higher median predicted 3-year TLI-free survival (99.25% vs. 99.15%, P < 0.001), the model identified a better plan than previous models. Interpretation: The deep learning model predicted TLI more precisely. The model-determined risk-based follow-up schedule detected the TLI earlier. The planning evaluation was refined because the model identified a better plan with a lower risk of TLI. Funding: The Sun Yat-sen University Clinical Research 5010 Program (2015020), Guangdong Basic and Applied Basic Research Foundation (2022A1515110356), Medical Scientific Research Foundation of Guangdong Province (A2022367), and Guangzhou Science and Technology Program (2023A04J1788).

Acute kidney injury associated with immune checkpoint inhibitors: A pharmacovigilance study.

BACKGROUND: Acute kidney injury (AKI) is a rare but severe adverse event of immune checkpoint inhibitors (ICIs). With the increasing reports of ICIs, it's necessary to put new insights into ICIs-related AKI. We conducted a systematic review of randomized controlled trials(RCTs) and a real-world study by extracting data from the US FDA Adverse Event Reporting System (FAERS) database. METHODS: We explored ICIs-related AKI events in RCTs available in ClinicalTrials.gov and electronic databases (PubMed, Cochrane Library, Embase) up to August 2021. Meta-analysis was performed by using risk ratios (RRs) with 95 %CIs. In a separate retrospective pharmacovigilance study of FAERs, disproportionality was analyzed using the proportional reports reporting odds ratio (ROR) and information components (IC). RESULTS: A total of 79 RCTs (500,09 patients) were included, and ICIs were associated with increased risk of all-grade (RR = 1.37, 95 %CI:1.14-1.65) and high-grade AKI (RR = 1.60, 95 %CI:1.16-2.20). Results of subgroup analysis indicated that RR of ICI-related AKI did not vary significantly by cancer type, treatment regimen (monotherapy or combination of ICIs), study design (double-blind or open-label), individual ICIs and publication status (published or unpublished). FAERS pharmacovigilance data identified 1918 cases of AKI related to ICIs therapy. ICIs were significantly associated with over-reporting frequencies of AKI (ROR = 2.38, 95 %CI:2.27-2.49; IC = 1.22, 95 %CI:1.16-1.27). The median onset time of AKI was 48 days, 77.5 % of patients discontinued the use of ICIs, and 15.9 % of patients resulted in death. CONCLUSIONS: These data suggest that ICIs were significantly associated with increased risk of AKI in both trial settings and clinical practice.

LncRNA Uc003xsl.1-Mediated Activation of the NFκB/IL8 Axis Promotes Progression of Triple-Negative Breast Cancer.

Aberrant activation of NFκB orchestrates a critical role in tumor carcinogenesis; however, the regulatory mechanisms underlying this activation are not fully understood. Here we report that a novel long noncoding RNA (lncRNA) Uc003xsl.1 is highly expressed in triple-negative breast cancer (TNBC) and correlates with poor outcomes in patients with TNBC. Uc003xsl.1 directly bound nuclear transcriptional factor NFκB-repressing factor (NKRF), subsequently preventing NKRF from binding to a specific negative regulatory element in the promoter of the NFκB-responsive gene IL8 and abolishing the negative regulation of NKRF on NFκB-mediated transcription of IL8. Activation of the NFκB/IL8 axis promoted the progression of TNBC. Trop2-based antibody-drug conjugates have been applied in clinical trials in TNBC. In this study, a Trop2-targeting, redox-responsive nanoparticle was developed to systematically deliver Uc003xsl.1 siRNA to TNBC cells in vivo, which reduced Uc003xsl.1 expression and suppressed TNBC tumor growth and metastasis. Therefore, targeting Uc003xsl.1 to suppress the NFκB/IL8 axis represents a promising therapeutic strategy for TNBC treatment. SIGNIFICANCE: These findings identify an epigenetic-driven NFκB/IL8 cascade initiated by a lncRNA, whose aberrant activation contributes to tumor metastasis and poor survival in patients with triple-negative breast cancer.

Prognostic role of pretreatment albumin-to-alkaline phosphatase ratio in locally advanced laryngeal and hypopharyngeal cancer: Retrospective cohort study.

Background: This study was designed to assess the prognostic significance of pretreatment albumin-to-alkaline phosphatase ratio (AAPR) in locally advanced laryngeal and hypopharyngeal cancer (LA-LHC). Materials and Methods: The clinical data of 341 patients with locally advanced laryngeal and hypopharyngeal cancer diagnosed between March 2007 and December 2018 were retrospectively collected and analyzed. The optimal cut-off value of AAPR for evaluating DFS was determined using the ROC curve, and 0.4912 was selected. Based on pretreatment AAPR values, patients were divided into two groups (low vs. high AAPR). Survival analysis was used to investigate the survival distribution between the groups. Univariate and multivariate analyses were performed to evaluate the prognostic value of AAPR. Based on the results of the multivariate analysis, we further developed models of DFS and OS. We assigned low AAPR, N1-3, age ≥65 years, and positive vascular invasion one score, respectively. Results: Survival analysis demonstrated that the survival of patients with low and high AAPR was significantly different (low vs. high AAPR: 5-year DFS, 46.0 vs. 71.9%, p<0.001; 5-year OS, 69.0 vs. 72.6%, p<0.001). Univariate and multivariate analyses further showed that pretreatment AAPR served as an independent indicator in LA-LHC. Moreover, survival analysis showed that patients with high model score had poorer DFS and OS (5-year DFS: 58.1, 42.7, 26.9 and 9.1% of score zero, one, two, and three respectively, p<0.001; 5-year OS: 63.0, 50.3, 34.1 and 28.6% of score zero, one, two, and three respectively, p<0.001). Conclusion: Pretreatment AAPR could be an independent prognostic indicator in patients with LA-LHC. Incorporating AAPR into the risk stratification model might better categorize patients with worse oncological outcomes and support treatment strategy making.

Large Tumor Size is an Indicator for the Timely Administration of Adjuvant Radiotherapy in Luminal Breast Cancer with Positive Lymph Node.

PURPOSE: The optimum timing of adjuvant radiotherapy for breast cancer patients who had undergone surgery remains unclear. The present study aimed to identify the clinical factors which could assist the selecting of time interval (TI) between surgery and adjuvant radiotherapy in luminal breast cancer with lymph node metastasis. PATIENTS AND METHODS: This retrospective study included 1054 luminal breast cancer patients with lymph node metastasis, diagnosed between May 2004 and December 2014, and treated with surgery followed by adjuvant therapy. Overall survival (OS) and disease-free survival (DFS) were compared between patients in the short and long TI groups. Multivariate analysis was performed to examine clinical factors associated with DFS. Subgroups analysis was further performed based on the significant predictors of DFS to explore the association of TI and tumor prognosis. RESULTS: For the whole group of patients, there was no difference in OS and DFS between patients with long and short TI. Multivariate analysis showed that age, N stage and tumor size were significant predictors of DFS. Subgroup analysis demonstrated that neither age nor N stage were informative in TI selection; in contrast, in patients with large tumors, a short TI was associated with better DFS than a long TI. In patients with small tumors, there was no significant association between TI and tumor prognosis. In the multivariable analysis, TI was independent predictor of DFS and local recurrence-free survival in patients with large tumors. CONCLUSION: Large tumor size is an indicator for the timely administration of adjuvant radiotherapy in luminal breast cancer with positive lymph node.

BRD7 inhibits tumor progression by positively regulating the p53 pathway in hepatocellular carcinoma.

Background: Bromodomain-containing protein 7 (BRD7) is identified as a transcriptional regulator and plays an important role in the development and progression of various tumors. Our previous study demonstrated that BRD7 acts as a potential tumor suppressor in hepatocellular carcinoma (HCC). However, the specific molecular mechanism underlying the BRD7-mediated inhibition of HCC progression remains poorly understood. Methods: We performed ChIP-seq analysis to investigate the gene network mediated by BRD7. Immunohistochemical analysis was performed to analyze potential associations between the p53 and BRD7 expression and the effect of their overexpression on disease pathogenesis and outcome. In addition, we performed biological function experiments to determine the effect of BRD7 and p53 on these functions that are central to tumorigenesis. Finally, we employed a BALB/c model for execution of xenograft transplants to examine the effect of either overexpressing or under-expressing BRD7 and p53 on tumor growth in mice injected with cells. Results: Our results suggested that BRD7 regulates the p53 pathway. Specifically, BRD7 was demonstrated to upregulate the transcription level of p53 by directly binding to the upstream regulatory region of the p53 transcriptional initiation site, thereby enhancing its promoter activity. Moreover, immunohistochemical analysis showed that wild-type p53 (WTp53) expression is positively associated with BRD7 expression and survival of patients with HCC. Additionally,changes of p53 expression could affect the tumor suppressive role of BRD7 on HCC cell proliferation, migration/invasion, cell-cycle, and tumor growth in vitro and in vivo. Furthermore, changes of BRD7 expression in HCC cells significantly altered the expression of p53 signal-related molecules such as p21, Bax, Bcl2, and cyclin D1, indicating that BRD7 may positively regulate activation of the p53 pathway. Conclusions: Collectively, our results indicated that BRD7 exerts anti-tumor effects in HCC through transcriptionally activating p53 pathway. These critical roles of BRD7may provide some promising diagnostic and therapeutic targets for HCC.

High Pretreatment LDH Predicts Poor Prognosis in Hypopharyngeal Cancer.

BACKGROUND: Elevated pretreatment lactate dehydrogenase (LDH) has been associated with poor prognosis in various malignancies; however, its prognostic role in hypopharyngeal cancer remains elusive. In this study, we aimed to assess the association between pretreatment LDH and clinical outcome of hypopharyngeal cancer. METHODS: We retrospectively collected 198 hypopharyngeal cancer patients treated with surgery in our institution between 2004 and 2018. The prognostic role of pretreatment LDH was explored by using univariate and multivariate analyses. Besides, subgroup analysis was performed based on T stage. RESULTS: Three-year and Five-year of disease-free survival (DFS, 67.0 vs. 57.4%, 65.8 vs. 39.8%, p = 0.007) and overall survival (OS, 74.8 vs. 68.9%, 66.8 vs. 50.8%, p = 0.006) exhibited significant differences between low LDH level and high LDH level groups. Univariate analysis showed that pretreatment elevated serum LDH served as an unfavorable determinant with regard to DFS and OS. Further multivariate analysis also confirmed that LDH was an independent predictor for DFS and OS. Additionally, N status and age were also found to be significantly associated with both DFS and OS. CONCLUSION: Pretreatment elevated serum LDH is an inferior prognostic factor for patients with hypopharyngeal cancer. These results should be validated by more multicenter and prospective studies.

Age as Indicator in the Selection of Surgery Modalities in Early Glottic Cancer.

PURPOSE: Local failure after endoscopic laryngeal surgery (ELS) for early glottic cancer mounts a challenge to researchers to investigate risk factors of recurrence. The present study was therefore designed to explore the prognostic factors in patients who underwent ELS for early glottic cancer. PATIENTS AND METHODS: We reviewed 328 patients with T1-2N0 glottic cancer who were treated with either ELS or open surgery between 2007 and 2018 at our institution. Survival, univariate and multivariate analyses were performed in different groups (ELS vs open surgery; < 65 vs ≥ 65 years). RESULTS: Age was discovered to be the independent prognostic factor of DFS for patients treated with ELS (HR = 3.673, p = 0.003), but not for patients who underwent open surgery. Survival analysis performed on young patients (< 65 years) showed that survival outcomes between different surgery modalities were significantly different (ELS vs open surgery: five-year DFS: 72.5 vs 84.7%, p = 0.034). Univariate and multivariate analyses further confirmed the finding, whereas these results did not appear in old patients (≥ 65 years). CONCLUSION: Young patients (< 65 years) treated with ELS had less favorable oncologic outcomes than those treated with open surgery. Young patients (< 65 years) are advised to consider open surgery over ELS.

Identifying Risk Factors for Regional Recurrence in Early-Stage Breast Cancer with pT1-2 and Negative Sentinel Lymph Node Biopsy.

BACKGROUND: Due to the low rate of regional recurrence (RR) in early-stage breast cancer with pT1-2 and negative sentinel lymph node biopsy (SLNB), no regional therapy is suggested for them. However, whether there is a subset of patients who were with high risk of regional failure and may benefit from regional treatment is still unknown. The current study was designed to identify the patients with high risk of RR, thereby providing clues for enhanced regional therapy. METHODS: We analyzed a total of 1124 breast cancer patients with pT1-2N0 from May 2004 to Dec 2014. All the patients were treated with breast-conservation surgery (BCS) and adjuvant whole-breast radiotherapy. The regional recurrence-free survival (RRFS), local regional recurrence-free survival (LRRFS), disease-free survival (DFS) and overall survival (OS) were assessed by using the Kaplan-Meier method. Cox proportional hazards regression was performed to detect factors in predicting the RRFS. RESULTS: In multivariable analysis, both T stage and molecular type were significant predictors of RRFS. Patients with T2 stage had a lower RRFS than those with T1stage. Triple-negative patients were more likely to suffer regional failure than the patients with other molecular types. The two predictors were then employed to divide all the patients into three groups based on the risk level of RR. Patients with both T2 and triple-negative molecular type had the lower RRFS, LRRFS, DFS and OS than the patients with one or no risk factor. CONCLUSION: For early-stage breast cancer patients with negative SLNB, those who were with both T2 stage and triple-negative molecular type had a high rate of RR and enhance regional therapy may be needed for them.