BACKGROUND:Sarcopenia is widely explored for its significance for predicting nasopharyngeal carcinoma (NPC) prognosis, yet current results are inconsistent. Consequently, this meta-analysis focused on investigating its precise role in predicting NPC prognosis. METHODS:We systemically retrieved studies in PubMed, Web of Science, Embase and Cochrane Library from inception to 17 March 2025. Sarcopenia was analysed for its role in predicting overall survival (OS) and progression-free survival (PFS) in NPC through determining combined hazard ratios (HRs) and 95% confidence intervals (CIs). Thereafter, associations of sarcopenia with NPC clinicopathological factors were estimated through aggregating odds ratios (ORs) with 95%CIs. RESULTS:There were eight studies with 5458 cases enrolled in this study. Based on the aggregated findings, sarcopenia was remarkably related to unfavourable OS (HR = 1.88, 95% CI = 1.47-2.40, p < .001) as well as PFS (HR = 2.03, 95%CI = 1.48-2.80, p < .001) of NPC. Moreover, sarcopenia was significantly associated with higher T stage (OR = 1.33, 95%CI = 1.12-1.59, p = .002). But it was not related to gender (OR = 0.87, 95%CI = 0.42-1.77, p = .694), N stage (OR = 1.00, 95%CI = 0.87-1.16, p = .952) and tumour-node-metastasis (TNM) stage (OR = 1.17, 95%CI = 0.94-1.46, p = .153) in NPC. CONCLUSIONS:This meta-analysis demonstrated that sarcopenia was a significant prognostic marker for poor OS and PFS in patients with NPC. Moreover, sarcopenia was also significantly associated with higher T stage of NPC.

While moderately hypofractionated radiotherapy (HFRT) has been recommended as the standard regimen in localized prostate cancer (LPCa) based on non-inferiority trials compared to conventionally fractionated radiotherapy(CFRT), the conclusions on its efficacy and toxicity have not been consistent among all trials. This study aims to systematically compare the efficacy and safety of HFRT with CFRT for LPCa based on the present randomized controlled trials. The longest follow-up data from all the trials were adopted. This research followed the steps outlined in the PRISMA statement for meta-analyses and systematic reviews. This study presents a meta-analysis of phase III trials comparing CFRT with HFRT for LPCa. The included trials reported relapse-free survival over five years and the incidence of acute or at least 3 years of late gastrointestinal (GI) and genitourinary (GU) toxicity. We were able to include 18 papers in our final analysis. There was no statistically significant difference in relapse-free survival after five years of treatment between the HFRT and CFRT groups. In subgroup analyses, with an α/β of 1.5, a higher equivalent dose of HFRT compared to CFRT is associated with improved relapse-free survival over five years. Acute GI toxicity of Grade 2 or worse was more common in the HFRT group compared to the CFRT group (p < 0.00001). The incidence of acute GI toxicity of Grade 2 or worse rose by 8.78

Acquired radioresistance critically challenges cervical cancer radiotherapy management. Clinically relevant radioresistant cell models remain scarce, and CXCL8's role in cervical cancer-despite its tumorigenic/therapy-resistant associations in other cancers-is poorly characterized. Two radioresistant cervical cancer cell strains were established. mRNA-seq and bioinformatics analysis of radiosensitivity regulators identified CXCL8 as a key mediator. In vitro, assays of cell viability, clone formation, apoptosis and cell cycle were conducted following transient transfection of cervical cancer radiotherapy-resistant cell strains with knockdown of CXCL8, as well as subsequent addition of exogenous CXCL8 to cervical cancer parental cell strains. Radioresistant cervical cancer cell lines (Hela-RR/Siha-RR) were established through clinical protocol-mimicking irradiation, validated via proliferation/clonogenic/cell cycle assays. mRNA-seq identified 50 co-upregulated and 54 co-downregulated genes in resistant strains, with CXCL8 among top differentially expressed genes (IL11, CXCL8, MMP1, HSPA8, CA9, PPFIA4, EDN2, GUCY1A2, EFNA3, TNFAIP6). qRT-PCR confirmed CXCL8, TNFAIP6, SRNA8 and PPFIA4 dysregulation. Cox regression analysis of 96 candidate radiosensitivity regulators prioritized CXCL8 among eight key genes in cervical cancer. GEPIA2 and immunohistochemistry revealed CXCL8 overexpression in tumors. Functional studies demonstrated CXCL8 knockdown sensitized resistant cells to radiation, while exogenous CXCL8 induced resistance in parental lines.

Aldo-keto reductase family 1 member C3 (AKR1C3) is a radioresistance gene in esophageal cancer. This study aimed to investigate the signaling pathways that mediate the regulatory role of AKR1C3 in the radioresistance of esophageal cancer cells. The protein levels of AKR1C3 in cancer tissue samples were compared between patients with radiosensitive and radioresistant esophageal cancer using immunohistochemical staining. AKR1C3-silenced stable KYSE170R esophageal cancer cells (KY170R-shAKR1C3) were established. Colony formation assay was employed to evaluate the radiosensitivity of cancer cells, while flow cytometry analysis was utilized to quantify reactive oxygen species (ROS) production in these cells. Additionally, Western blotting was conducted to determine protein expression levels. AKR1C3 protein exhibited significantly higher expression in radioresistant cancer tissue samples compared to radiosensitive samples. AKR1C3 silencing promoted radiosensitivity and ROS production of KYSE170R cells. At 32 h after X-ray radiation, the levels of total and phosphorylated ERK1/2, JNK, and AKT proteins were significantly elevated in KYSE170R-shAKR1C3 cells compared to untransfected KYSE170R cells. The inhibitor of AKR1C3 remarkably enhanced the radiosensitivity of KYSE170R cells. Conversely, treatment with either a MEK inhibitor or an AKT inhibitor significantly increased the radioresistance of KYSE170R-shAKR1C3 cells. Our results suggest that AKR1C3 mediates radioresistance of KYSE170R cells possibly through MAPK and AKT signaling.

BACKGROUND:Immunogenic cell death (ICD) is a type of regulated cell death that is capable of initiating an adaptive immune response. Induction of ICD may be a potential treatment strategy, as it has been demonstrated to activate the tumor-specific immune response. AIMS:The biomarkers of ICD and their relationships with the tumor microenvironment, clinical features, and immunotherapy response are not fully understood in a clinical context. Therefore, we conducted pan-cancer analyses of ICD gene signatures across 33 cancer types from The Cancer Genome Atlas database. METHODS AND RESULTS:We identified key genes that had strong relationships with survival and the tumor microenvironment, contributing to a better understanding of the role of ICD genes in cancer therapy. In addition, we predicted therapeutic agents that target ICD genes and explored the potential mechanisms by which gemcitabine induce ICD. Moreover, we developed an ICD score based on the ICD genes and found it to be associated with patient prognosis, clinical features, tumor microenvironment, radiotherapy access, and immunotherapy response. A high ICD score was linked to the immune-hot phenotype, while a low ICD score was linked to the immune-cold phenotype. CONCLUSION:We uncovered the potential of ICD gene signatures as comprehensive biomarkers for ICD in pan-cancer. Our research provides novel insights into immuno-phenotypic assessment and cancer therapeutic strategies, which could help to broaden the application of immunotherapy to benefit more patients.

BACKGROUND:The prognostic significance of the systemic inflammatory response index (SIRI) in patients with cancer receiving programmed cell death 1 (PD-1)/PD-1 ligand 1 (PD-L1) immune checkpoint inhibitors (ICIs) has been widely investigated; however, the results have been conflicting. As such, the present meta-analysis aimed to analyze the precise significance of the SIRI in predicting prognosis in patients with cancer undergoing ICI therapy. METHODS:A comprehensive literature search of the Web of Science, PubMed, Embase, and Cochrane Library databases for relevant studies, published from inception to April 25, 2024, was performed. The SIRI was analyzed for its prognostic utility in patients undergoing ICI therapy by calculating combined hazard ratios (HRs) and corresponding 95% confidence intervals (CIs). RESULTS:Six studies comprising 1133 patients were included in the analysis. Pooled data revealed that a higher SIRI was significantly associated with poor overall survival (OS) (HR 1.96 [95% CI 1.55-2.47]; p < 0.001) and progression-free survival (PFS) (HR 1.41 [95% CI 1.19-1.67]; p < 0.001) for patients who underwent PD-1/PD-L1 ICI treatment. Subgroup analysis revealed that SIRI was markedly associated with dismal OS and PFS, independent of sample size, cut-off value, and survival analysis (p < 0.05). The findings were verified to be robust against publication bias and sensitivity analyses. CONCLUSION:In summary, an elevated SIRI was significantly associated with OS and PFS in patients with cancer undergoing PD-1/PD-L1 ICI treatment. SIRI may a candidate indicator for predicting the prognosis of patients undergoing ICI therapy.

Exploring the mechanism of breast cancer metastasis and searching for new drug therapeutic targets are still the focuses of current research. RNA-binding proteins (RBPs) may affect breast cancer metastasis by regulating alternative splicing (AS) during epithelial-mesenchymal transition (EMT). We hypothesised that during EMT development in breast cancer cells, the expression level of RBPs and the gene AS pattern in the cell were significantly changed on a genome-wide scale. Using GEO database, this study identified differentially expressed RBPs and differential AS events at different stages of EMT in breast cancer cells. By establishing the correlation network of differential RBPs and differential AS events, we found that RBM47, PCBP3, FRG1, SRP72, RBMS3 and other RBPs may regulate the AS of ITGA6, ADGRE5, TNC, COL6A3 and other cell adhesion genes. By further analysing above EMT-related RBPs and AS in breast cancer tissues in TCGA, it was found that the expression levels of ADAT2, C2orf15, SRP72, PAICS, RBMS3, APOBEC3G, NOA1, ACO1 and the AS of TNC and COL6A3 were significantly correlated with the prognosis of breast cancer patients. The expression levels of all 8 RBPs were significantly different in breast cancer tissues without metastasis compared with normal breast tissues. Conclusively, eight RBPs such as RBMS3 and AS of TNC and COL6A3 could be used as predictors of breast cancer prognosis. These findings need to be further explored as possible targets for breast cancer treatment.

PurposeIt is difficult to contour nerve structures with the naked eye due to poor differentiation between the nerve structures with other soft tissues on CT images. Magnetic resonance neurography (MRN) has the advantage in nerve visualization. The purpose of this study is to identify one MRN sequence to better assist the delineation of the lumbosacral plexus (LSP) nerves to assess the radiation dose to the LSP using the magnetic resonance (MR)/CT deformable coregistration technique.MethodsA total of 18 cases of patients with prostate cancer and one volunteer with radiation-induced lumbosacral plexopathy (RILSP) were enrolled. The data of simulation CT images and original treatment plans were collected. Two MRN sequences (Lr_NerveVIEW sequence and Cs_NerveVIEW sequence) were optimized from a published MRN sequence (3D NerveVIEW sequence). The nerve visualization ability of the Lr_NerveVIEW sequence and the Cs_NerveVIEW sequence was evaluated via a four-point nerve visualization score (NVS) scale in the first 10 patients enrolled to determine the better MRN sequence for assisting nerve contouring. Deformable registration was applied to the selected MRN sequence and simulation CT images to get fused MR/CT images, on which the LSP was delineated. The contouring of the LSP did not alter treatment planning. The dosimetric data of the LSP nerve were collected from the dose–volume histogram in the original treatment plans. The data of the maximal dose (Dmax) and the location of the maximal radiation point received by the LSP structures were collected.ResultsThe Cs_NerveVIEW sequence gained lower NVS scores than the Lr_NerveVIEW sequence (Z=-2.887, p=0.004). The LSP structures were successfully created in 18 patients and one volunteer with MRN (Lr_NerveVIEW)/CT deformable registration techniques, and the LSP structures conformed with the anatomic distribution. In the patient cohort, the percentage of the LSP receiving doses exceeding 50, 55, and 60 Gy was 68% (12/18), 33% (6/18), and 17% (3/18), respectively. For the volunteer with RILSP, the maximum irradiation dose to his LSP nerves was 69 Gy.ConclusionThe Lr_NerveVIEW MRN sequence performed better than the Cs_NerveVIEW sequence in nerve visualization. The dose in the LSP needs to be measured to understand the potential impact on treatment-induced neuropathy.

Background: There are few randomised prospective data or guidelines for the treatment of neuroendocrine cervical cancer (NECC). In addition, the role of radiotherapy (RT) in NECC remains controversial. We used the Surveillance Epidemiology and End Results (SEER) database to investigate the role of RT for the treatment of NECC. Particular attention was paid to the different role of RT in patients with or without a metastasis (M1 or M0). Methods: The SEER database was queried for studies on NECC. We limited the year of diagnosis to the years 2000 to 2015. A Pearson’s two-sided Chi-squared test, the Kaplan–Meier method and Cox regression analysis models were used for statistical analyses. The overall survival (OS) was studied for the overall group and between-subgroup groups. Results: NECC was an aggressive disease with a mean OS of only 46.3 months (range of 0–196 months, median of 23 months). No significant differences were shown between the surgery (S) and S + RT groups ( p = 0.146) in the M0 (without metastasis) arm. However, there was a statistically significant difference in OS between the S and S + RT groups in the M1 (with metastasis) arm (median of 44.6 months for the S group and 80.9 months for the S + RT group), p = 0.004. The mean survival was significantly longer for M0 patients than for M1 patients when treated with S only (S arm), that is, 82.1 months versus 44.6 months, respectively (log-rank p = 0.000). We also noted that when patients received adjuvant RT (S + RT arm), there were no significant differences between the M0 and M1 groups (median of 90.6 and 81.0 months, p = 0.704, respectively). Age at diagnosis, chemotherapy, T stage and N stage were significant factors for OS in the M0 arm. Interestingly, radiotherapy was the only significant factor for OS with a multivariate HR for death of 0.502 (95% CI 0.206–0.750, p = 0.006) in the M1 arm. Conclusions: RT may be carefully used in patients who are negative for metastases. Using SEER data, we identified a significant survival advantage with the combination of radiotherapy and surgery in NECC with metastases. This suggests that active local treatment should be conducted and has a significant impact on OS, even if a distant metastasis has occurred.

Maternally expressed 3 (MEG3) and RNA binding motif single stranded interacting protein 3 (RBMS3) are abnormally expressed in breast cancer susceptibility genes (BRCA), but the mechanism of the two in breast cancer (BC) is unclear. By performing in vivo and in vitro experiments, we found that MEG3 and RBMS3 were low-expressed, negatively correlated with high-expressed miR-141-3p, were positively correlated with each other in BC. MEG3 targeted miR-141-3p, and miR-141-3p targeted RBMS3. MEG3, which was mainly distributed in BC cytoplasm, could down-regulate miR-141-3p and up-regulate RBMS3, and reverse effect of miR-141-3p on related gene expressions and on promoting cancer development. Overexpressed MEG3 inhibited growth of xenografts, promoted cell apoptosis via regulating apoptosis related factors, and up-regulated RBMS3 expression but down-regulated miR-141-3p. The findings of this study showed that MEG3 inhibited proliferation and promoted apoptosis of BC cells through the miR-141-3p/RBMS3 axis, and MEG3 inhibited growth of xenografts through miR-141-3p.

Background Locally advanced cervical cancer (LACC), FIGO stage equal or more than IB1 is treated with chemotherapy and external beam radiotherapy followed by brachytherapy. However, treatment failure and distant metastasis still remain a major problem. Bioinformatics analysis was used to comprehensively evaluate the intrinsic resistance to treatment in LACC. We selected cytokine-like protein 1 (Cytl1), a novel cytokine, for validation by immunochemistry assays (IHC). Materials and methods The Gene Expression Omnibus (GEO) and the cancer genome atlas (TCGA) were analyzed to identify significant prognostic differentially expressed genes (DEGs). The CIBERSORT and ESTIMATE algorithms was performed to validate the genetic risk score model. A total of 113 tissues were evaluated by IHC. Kaplan-Meier curves and the log-rank test were applied for survival analysis. Results One thousand and twenty-one genes, consisting of 663 upregulated and 358 downregulated genes, were screened out in the GSE56363 cohort. KEGG and GO pathway enrichment methods was used to analyze the abundant DEGs to find the common characteristics. A genetic risk score model which formed by fifteen genes was established from GSE56363 and validated in the TCGA discovery set. We performed the CIBERSORT and ESTIMATE algorithms to find the difference of immune related signature between the high- and low-risk group to quantify the prognostic value of the fifteen-gene risk model. Among the 22 immune cell types, CD8 T cells, resting CD4 T cells, resting mast cells, activated mast cells, monocytes, neutrophil granulocyte were significantly different between high- and low-risk group. Immune-checkpoints (LAG3 and PDCD1) were highly expressed, and associated with poor prognosis in LACC. IHC demonstrated that cytl1 overexpression was positively associated with poor overall survival (P = 0.01). Cytl1 expression was closely correlated with CD8+T cell low-expression in LACC (r = 0.889, P = 0.066). Conclusion This study identified a novel fifteen-gene signature biomarker for predicting the treatment effect of LACC. Moreover, the current results demonstrated that cytl1was overexpressed and associated with poor prognosis in LACC. Cytl1 may be a potential prognostic marker and novel therapeutic target for LACC.

Background It is not known which risk stratification system has the best discrimination ability for predicting prostate cancer death. Methods We identified patients with non-metastatic primary prostate adenocarcinoma diagnosis between 2004 and 2015 using the Surveillance, Epidemiology, and End Results database. Patients were categorized in different risk groups using the three frequently used risk stratification systems of the National Comprehensive Cancer Network guideline (NCCN-g), American Urological Association guideline (AUA-g), and European Association of Urology guideline (EAU-g), respectively. Associations between risk classification and prostate cancer-specific mortality (PCSM) were determined using Kaplan–Meier analyses and multivariable regression with Cox proportional hazards model. Area under the receiver operating characteristics curve (AUC) analyses were used to test the discrimination ability of the three risk grouping systems. Results We analyzed 310,062 patients with a median follow-up of 61 months. A total of 36,368 deaths occurred, including 6,033 prostate cancer deaths. For all the three risk stratification systems, the risk groups were significantly associated with PCSM. The AUC of the model relying on NCCN-g, AUA-g, and EAU-g risk stratification systems for PCSM at specifically 8 years were 0.818, 0.793, and 0.689 in the entire population; 0.819, 0.795, and 0.691 in Whites; 0.802, 0.777, and 0.681 in Blacks; 0.862, 0.818, and 0.714 in Asians; 0.845, 0.806, and 0.728 in Chinese patients. Regardless of the age, marital status, socioeconomic status, and treatment modality, AUC of the model relying on NCCN-g and AUA-g for PCSM was greater than that relying on EAU-g; AUC of the model relying on NCCN-g system was greater than that of the AUA-g system. Conclusions The NCCN-g and AUA-g risk stratification systems perform better in discriminating PCSM compared to the EAU-g system. The discrimination ability of the NCCN-g system was better than that of the AUA-g system. It is recommended to use NCCN-g to evaluate risk groups for prostate cancer patients and then provide more appropriate corresponding treatment recommendations.

The occurrence of radioresistance is a clinical obstacle to endometrial cancer (EC) treatment and induces tumor relapse. In this study, we found that tumor-associated macrophages (TAMs) enriched in EC specimens were determined to present an M2-like phenotype. In vitro, the coculture of M2-polarized macrophages significantly downregulated the radiosensitivity of EC cells by releasing exosomes. Hsa_circ_0001610 was found to be abundant in exosomes derived from M2-polarized macrophages (EXOs), and hsa_circ_0001610 knockdown eliminated the reduction effect of EXOs on the radiosensitivity of EC cells. The following mechanism research revealed that hsa_circ_0001610 functioned as the competing endogenous RNA of miR-139-5p, thereby upregulating cyclin B1 expression, which is a vital pusher of radioresistance in several types of cancer by regulating the cell cycle. Hsa_circ_0001610 overexpression reduced the radiosensitivity of EC cells, which was then reversed by miR-139-5p overexpression. In vivo, the promotion effect of EXOs on xenograft tumor growth in nude mice treated with irradiation was further reinforced after hsa_circ_0001610 overexpression. In conclusion, TAM-derived exosomes transferred hsa_circ_0001610 to EC cells, and the overexpressed hsa_circ_0001610 in EC cells released cyclin B1 expression through adsorbing miR-139-5p, thereby weakening the radiosensitivity of EC cells.

The prognostic value of the systemic immune-inflammation index (SII) in patients with pancreatic cancer is conflicting according to previous investigations. Therefore, we performed a meta-analysis to explore the association between SII and pancreatic cancer prognosis. Electronic databases were searched for studies exploring the association of SII with prognostic outcomes in pancreatic cancer. The endpoints were overall survival (OS), disease-free survival (DFS), recurrence-free survival (RFS), progression-free survival (PFS), cancerspecific survival (CSS), and clinicopathological parameters. The prognostic value of SII was estimated by hazard ratio (HR) or odds ratio (OR) with a 95% confidence interval (CI). Nine studies containing 11 cohorts with 2,365 subjects in total were included in this meta-analysis. Elevated SII was associated with poor OS (HR=1.50, 95% CI=1.15-1.96, p=0.002), RFS/PFS/DFS (HR=1.52, 95% CI=1.01-2.28, p=0.045), and CSS (HR=2.60, 95% CI=1.65-4.09, p < 0.001) in patients with pancreatic cancer. Additionally, there was no significant association between SII and other parameters in pancreatic cancer such as sex, tumor location, lymph node metastasis, tumor-nodemetastasis stage, vascular invasion, and grade. This meta-analysis suggested that elevated SII was a significant prognostic marker for short-term and long-term survival outcomes in patients with pancreatic cancer.

Background: The purpose of this study was to develop prognostic nomograms from a cohort of patients with triple-negative breast cancer (TNBC) with histology of infiltrating duct carcinoma (IDC) by correlating their clinical and pathological parameters with the rates of disease-free survival (DFS) and overall survival (OS). Methods: We retrospectively analyzed TNBC patients with histology of IDC at our institution between 2009 and 2012. Age, family history, menopausal status, surgery type, T stage, N stage, histological grade, vascular invasion, perineural invasion, cytokeratin 5/6 status, Ki-67 expression, and epithelial cadherin (E-cadherin) status were analyzed. Predictors were used in multivariable logistic regression analysis to develop a nomogram to predict DFS and OS rates. The nomograms were then subjected to internal validation, with external validation of the nomogram for predicting OS using separate cohorts of TNBC patients known from the Cancer Genome Atlas (TCGA) database. Using the concordance index (C-index) with calibration curves, the predictive accuracy and discriminative ability were calculated. Results: A total of 242 eligible TNBC patients were included for analysis. The median follow-up time was 70.73 months. Of the patients, 32.6%, 42.6%, and 24.8% had stage I, II, and III disease, respectively. The 3 and 5-year survival rates were 81.0% and 76.5% for DFS, and 86.5% and 81.1%, for OS, respectively. Age, T stage, N stage, and E-cadherin status were found to be risk factors. The nomograms based on those risk factors accurately predicted the 3and 5-year survival rates. The C-index was 0.798 and 0.821 for DFS and OS, respectively. Besides, the nomogram for OS showed relatively reliable performance in stratifying different risk groups of patients in training and validation cohorts identified from the TCGA database. The C-index reached 0.843. DFS validation was not completed, as there was insufficient data. Conclusions: Using clinicopathological information, we produced a prognostic nomogram that accurately predicts the 3 and 5-year DFS and OS for patients with TNBC with histology of IDC. More external confirmation is required.

Abstract Background Programmed death-ligand 1 (PD-L1) was the first identified ligand of programmed death-1 (PD-1). PD-1/PD-L1 interactions inhibit T cell-mediated immune responses, limit cytokine production, and promote tumor immune escape. Recently, many studies have investigated the prognostic value of PD-L1 expression in patients with melanoma. However, the results of these analyses remain a subject of debate. We have therefore carried out a meta-analysis to identify the prognostic role of PD-L1 in melanoma. Methods A thorough medical literature search was performed in the databases PubMed, Web of Science, and Embase until October 2019. The pooled hazard ratios (HRs) and 95% confidence intervals (95% CIs) were calculated to evaluate the correlation between PD-L1 overexpression and prognosis. Publication bias was evaluated using Begg’s test and Egger’s test. Results Thirteen articles with 1062 enrolled patients were included in this meta-analysis. High PD-L1 expression did not correlate with overall survival (OS) (HR = 0.93, 95% CI 0.57–1.52, P = 0.781) or progression-free survival (PFS) (HR = 0.82, 95% CI 0.43–1.54, P = 0.535). However, PD-L1 overexpression correlated with the absence of lymph node (LN) metastasis (OR = 0.46, 95% CI 0.22–0.95, P = 0.036). Further, there was no significant relationship between PD-L1 expression and sex (OR = 1.29, 95% CI 0.90–1.84, P = 0.159), age (OR = 0.90, 95% CI 0.51–1.57, P = 0.708), or Eastern Cooperative Oncology Group Performance Status (OR = 0.55, 95% CI 0.06–4.83, P = 0.592). Conclusions This meta-analysis suggested that PD-L1 expression did not predict an inferior prognosis in patients with melanoma. However, high PD-L1 expression was associated with absence of LN metastasis in such patients.

Department of Radiation Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, People’s Republic of China Introduction: The present study aimed to explore the role of miR-499a-5p and its molecular mechanism in cervical cancer (CC). Methods: Quantitative real-time PCR (QRT-PCR) andWestern blotting were performed to detect the expression of miR-499a-5p and eukaryotic translation initiation factor 4E (eIF4E) in CC tissues and cell lines. The proliferation, migration, and invasion of CC cells were detected by MTTassay, wound healing assay, and Transwell assay. Apoptosis was evaluated by flow cytometry and alterations of apoptosis-related genes. The effect of miR-499a-5p on epithelial–mesenchymal transition (EMT) was examined by determining the protein levels of EMT-associated genes. Then, colony formation assay was used to determine the radiosensitivity of CC cells. A dualluciferase reporter assay was performed to confirm the direct target of miR-499a-5p. Results: MiR-499a-5p was significantly downregulated in CC tissues and cell lines. Overexpression of miR-499a-5p or eIF4E knockdown markedly inhibited cell proliferation, invasion, migration, and EMT, and enhanced apoptosis. eIF4E was predicted and verified as a target gene of miR-499a-5p. The influence of miR-499a-5p upregulation on proliferation, apoptosis, invasion, migration, EMT, and radiosensitivity was abrogated by eIF4E overexpression. Discussion: MiR-499a-5p promoted the apoptosis and radiosensitivity and inhibited proliferation, invasion, migration, and EMT by directly targeting eIF4E in CC cells.

Purpose This study aims to identify predictive local recurrence risk factors and site-specific local recurrence pattern of upper tract urothelial carcinoma (UTUC) with different primary tumor locations. Methods Three hundred and eighty-nine UTUC patients with radical nephroureterectomy were included in this study. Univariate and multivariate Cox proportional hazards regressions were performed to measure the risk of local recurrence. We also mapped the position of local recurrence sites stratified by primary tumor locations. Results A total of 73 patients (18.7%) developed local recurrence within a median follow-up of 41 months (range, 3-80 months). For patients with local recurrence, the median interval of local recurrence was 9 months. Ureter tumor, multifocality, T stage, G grade, lymph node metastasis (LNM), lymph node dissection (LND), and lymph vascular invasion (LVI) were all significantly associated with increased local recurrence by univariable analyses ( P < 0.05). Only multifocality, T3–4, G3, and LNM remained independent predictors of increased local recurrence by multivariable analyses. Adjuvant radiotherapy could reduce the local recurrence (HR = 0.177; 95% CI 0.064-0.493, P = 0.001). Patients with local recurrence had poorer cancer-specific survival (4-year cancer-specific survival rate 36 ± 7.5% vs 88.4 ± 2.2%, P = 0.000). We evaluated local recurrence pattern stratified by tumor locations. Para-aortic lymph node region was the most common recurrence area for all the patients. Left-sided UTUC had more than 70% recurrent lymph nodes in the left para-aortic region (LPA). For right-sided UTUC patients, recurrent para-aortic lymph nodes distributed in the LPA (33.3%), aortocaval (AC) (41.5%), and right paracaval (RPC) (25.2%) regions. Recurrence in the internal and external iliac regions was only found in the distal ureter group ( P < 0.05). Renal pelvic fossa recurrence was only found in renal pelvic tumor (22.2%, P = 0.007). The ureter tumor bed recurrence rate was higher for ureter patients ( P = 0.001). Conclusions Multifocality, T3–4, G3, and LNM are predictors of higher local recurrence rate of UTUC. Adjuvant radiotherapy can reduce local recurrence rate. Local recurrence patterns are different according to primary tumor locations.

INTRODUCTION:The present study aimed to explore the role of miR-499a-5p and its molecular mechanism in cervical cancer (CC).METHODS:Quantitative real-time PCR (QRT-PCR) and Western blotting were performed to detect the expression of miR-499a-5p and eukaryotic translation initiation factor 4E (eIF4E) in CC tissues and cell lines. The proliferation, migration, and invasion of CC cells were detected by MTT assay, wound healing assay, and Transwell assay. Apoptosis was evaluated by flow cytometry and alterations of apoptosis-related genes. The effect of miR-499a-5p on epithelial-mesenchymal transition (EMT) was examined by determining the protein levels of EMT-associated genes. Then, colony formation assay was used to determine the radiosensitivity of CC cells. A dual-luciferase reporter assay was performed to confirm the direct target of miR-499a-5p.RESULTS:MiR-499a-5p was significantly downregulated in CC tissues and cell lines. Overexpression of miR-499a-5p or eIF4E knockdown markedly inhibited cell proliferation, invasion, migration, and EMT, and enhanced apoptosis. eIF4E was predicted and verified as a target gene of miR-499a-5p. The influence of miR-499a-5p upregulation on proliferation, apoptosis, invasion, migration, EMT, and radiosensitivity was abrogated by eIF4E overexpression.DISCUSSION:MiR-499a-5p promoted the apoptosis and radiosensitivity and inhibited proliferation, invasion, migration, and EMT by directly targeting eIF4E in CC cells.

Purpose We identified the risk predictors related to prostate cancer (PCa) metastasis using contemporary data in a community setting. Then, we assessed the performance of indications for bone imaging recommended from the NCCN, AUA and EAU guidelines. Methods Using the Surveillance, Epidemiology, and End Results database (2010–2015), we collected clinicopathological information from PCa patients. The associated risk factors found by multivariate analyses were used to establish forest plots and nomograms for distant metastasis (DM) and bone(s)-only metastasis (BM). We next evaluated the NCCN, AUA and EAU guidelines indications for the discovery of certain subgroups of patients who should receive bone imaging. Results A total of 120,136 patients were eligible for analysis, of which 96.7% had no metastasis. The odds ratios of positive DM and BM results were 13.90 times and 15.87 times higher in patients with a histologic grade group (GG) 5 than in the reference group. The concordance index of the nomograms based on race, age, T/N stage, PSA, GG, percentage of positive scores for predicting DM and BM was 0.942 and 0.928, respectively. Performance of the NCCN, AUA and EAU guidelines was high and relatively similar in terms of sensitivity (93.2–96.9%) and negative predictive value (99.8–99.9%). NCCN guidelines had the highest accuracy, specificity and positive likelihood ratio, while negative likelihood ratio was lowest in AUA guideline. Conclusion Histologic GG 5 was the foremost factor for DM and BM. NCCN-based recommendations may be more rational in clinical practice. Nomograms predicting metastasis demonstrate high accuracy.