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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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Resistance to radiotherapy is frequently encountered in clinic, leading to poor prognosis of cancer patients. Long noncoding RNAs (lncRNAs) play important roles in the development of radioresistance due to their functions in regulating the expression of target genes at both transcriptional and posttranscriptional levels. Exploring key lncRNAs and elucidating the mechanisms contributing to radioresistance are crucial for the development of effective strategies to reverse radioresistance, which however remains challenging. Here, actin filament‐associated protein 1 antisense RNA1 (lncAFAP1‐AS1) is identified as a key factor in inducing radioresistance of triple‐negative breast cancer (TNBC) via activating the Wnt/β‐catenin signaling pathway. Considering the generation of a high concentration of reduction agent glutathione (GSH) under radiation, a reduction‐responsive nanoparticle (NP) platform is engineered for effective lncAFAP1‐AS1 siRNA (siAFAP1‐AS1) delivery. Systemic delivery of siAFAP1‐AS1 with the reduction‐responsive NPs can synergistically reverse radioresistance by silencing lncAFAP1‐AS1 expression and scavenging intracellular GSH, leading to a dramatically enhanced radiotherapy effect in both xenograft and metastatic TNBC tumor models. The findings indicate that lncAFAP1‐AS1 can be used to predict the outcome of TNBC radiotherapy and combination of systemic siAFAP1‐AS1 delivery with radiotherapy can be applied for the treatment of recurrent TNBC patients. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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., (©2021 The Authors; Published by the American Association for Cancer Research.)

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., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Resistance to radiotherapy is frequently encountered in clinic, leading to poor prognosis of cancer patients. Long noncoding RNAs (lncRNAs) play important roles in the development of radioresistance due to their functions in regulating the expression of target genes at both transcriptional and posttranscriptional levels. Exploring key lncRNAs and elucidating the mechanisms contributing to radioresistance are crucial for the development of effective strategies to reverse radioresistance, which however remains challenging. Here, actin filament-associated protein 1 antisense RNA1 (lncAFAP1-AS1) is identified as a key factor in inducing radioresistance of triple-negative breast cancer (TNBC) via activating the Wnt/ β -catenin signaling pathway. Considering the generation of a high concentration of reduction agent glutathione (GSH) under radiation, a reduction-responsive nanoparticle (NP) platform is engineered for effective lncAFAP1-AS1 siRNA (siAFAP1-AS1) delivery. Systemic delivery of siAFAP1-AS1 with the reduction-responsive NPs can synergistically reverse radioresistance by silencing lncAFAP1-AS1 expression and scavenging intracellular GSH, leading to a dramatically enhanced radiotherapy effect in both xenograft and metastatic TNBC tumor models. The findings indicate that lncAFAP1-AS1 can be used to predict the outcome of TNBC radiotherapy and combination of systemic siAFAP1-AS1 delivery with radiotherapy can be applied for the treatment of recurrent TNBC patients., Competing Interests: The authors declare no conflict of interest., (© 2020 The Authors. Published by Wiley‐VCH GmbH.)

To explore clinical characteristics which could be applied to predict pathologic complete response (pCR) for patients with locally advanced rectal cancer treated with neoadjuvant chemoradiotherapy (neo-CRT) and total mesorectal excision (TME). 297 patients with locally advanced rectal cancer (cT3-4 or cN+) who were treated with neo-CRT followed by TME were retrospectively reviewed. Clinical characteristics including age, gender, tumor distance from anus, serum CEA, hemoglobin levels before treatment and clinical TN stage were used to investigate the association with pCR after neo-CRT. Seventy-nine (26.6%) patients achieved pCR after neo-CRT. pCR were achieved in 42 (34.4%) patients in cT1-3 stage and 37 (21.1%) in cT4 stage. pCR rate was 36.4% and 16.4% for patients with pre-treatment serum CEA ≤5.33ng/ml and >5.33ng/ml, respectively. Uni- and multi-variate analyses revealed that pre-treatment serum CEA level ≤5.33ng/ml and clinical T stage, (i.e., cT1-3 versus cT4) were highly correlated with pCR (p < 0.05). Clinical T stage and pre-treatment serum CEA level were strongly associated with pCR for patients with locally advanced rectal cancer treated with neo-CRT followed by TME which could be applied as clinical predictors for pCR., Competing Interests: Competing Interests: The authors have declared that no competing interest exists.

Purpose: To investigate predictive value of APAF-1 and COX-2 expression in pathologic complete response (pCR) for patients with rectal adenocarcinoma (RAC) who were treated with neoadjuvant chemoradiotherapy (neo-CRT) followed by total mesorectal excision (TME).  , Materials and Methods: Immunohistochemistry assay was used to detect expression of APAF-1 and COX-2 in paraffin-wax embedded tissues obtained before neo-CRT for patients with RAC. A 5-point tumor-regression grade (TRG) based on the ratio of residual tumor to fibrosis according to Dworak's scoring system was used to assess neo-CRT response. The relationship between expression of APAF-1 and COX-2 genes and pCR was explored., Results: pCR (TRG4) was observed in 23 patients (28.0%). pCR were more likely to be achieved for those with APAF-1 over-expression or lower expression of COX-2. pCR rate in patients with combination of high APAF-1 and low COX-2 expression was 56.0%, significantly higher than those with other combination of APAF1 and COX-2 expression. Multivariate analysis showed that over-expression of APAF-1 and suppressed expression of COX-2 were independent predictive factors for pCR., Conclusion: Immunohistochemical evaluation of APAF-1 and COX-2 expression on pretreatment specimen may be used to predict pCR to neo-CRT in patients with RAC. The potential of the markers in monitoring pCR patient merits further investigation., Competing Interests: No potential conflicts of interest were disclosed.

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.