Prognostic significance of pan-immune-inflammation value in hepatocellular carcinoma treated by curative radiofrequency ablation: potential role for individualized adjuvant systemic treatment.

BACKGROUND: This study aimed to explore the prognostic role of pan-immune-inflammation value (PIV) and develop a new risk model to guide individualized adjuvant systemic treatment following radiofrequency ablation (RFA) for early-stage hepatocellular carcinoma (HCC). MATERIALS AND METHODS: Patients with early-stage HCC treated by RFA were randomly divided into training cohort A (n = 65) and testing cohort B (n = 68). Another 265 counterparts were enrolled into external validating cohort C. Various immune-inflammatory biomarkers (IIBs) were screened in cohort A. Prognostic role of PIV was evaluated and validated in cohort B and C, respectively. A nomogram risk model was built in cohort C and validated in pooled cohort D. Clinical benefits of adjuvant anti-angiogenesis therapy plus immune checkpoint inhibitor (AA-ICI) following RFA was assessed in low- and high-risk groups. RESULTS: The cutoff point of PIV was 120. High PIV was an independent predictor of unfavorable recurrence-free survival (RFS) and overall survival (OS). RFS and OS rates of patients with high PIV were significantly lower than those with low PIV both in cohort B (PRFS=0.016, POS=0.011) and C (PRFS<0.001, POS<0.001). The nomogram model based on PIV, tumor number and BCLC staging performed well in risk stratification in external validating cohort C. Adjuvant AA-ICI treatment showed an added benefit in OS (p = 0.011) for high-risk patients. CONCLUSIONS: PIV is a feasible independent prognostic factor for RFS and OS in early-stage HCC patients who received curative RFA. The proposed PIV-based nomogram risk model could help clinicians identify high-risk patients and tailor adjuvant systemic treatment and disease follow-up scheme.

Key findingsHigh pan-immune-inflammation value (PIV) is an independent indicator of unfavorable recurrence-free survival (RFS) and overall survival (OS) for early-stage hepatocellular carcinoma (HCC) patients who received curative radiofrequency ablation (RFA).Adjuvant anti-angiogenesis target therapy plus immune checkpoint inhibitor (AA-ICI) treatment showed added benefit in OS for the high-risk patients defined by a nomogram risk model based on PIV, tumor number and BCLC staging.What is known and what is new?Inflammation and impaired host immunity are associated with carcinogenesis and progression of HCC. Increasing evidences showed that immune-inflammatory biomarkers (IIBs) had prognostic roles in early-stage HCC patients who received RFA. However, prognostic potential of PIV has not been determined in this setting.Herein, high PIV was first reported to be an independent risk factor of poor RFS and OS in early-stage HCC patients treated by curative RFA and helped to discriminate patients between low- and high-risk groups. Adjuvant AA-ICI treatment following RFA was beneficial to OS of patients in the high-risk group.What is the implication, and what should change now?For early-stage HCC with high-risk factors (high PIV, multiple tumor foci and more advanced BCLC stage), intensive follow-up and adjuvant systemic therapy following curative RFA were warranted.

Liver-directed moderately hypo-fractionated radiotherapy combined with pembrolizumab and bevacizumab for advanced hepatocellular carcinoma: a retrospective observational study of 23 cases.

Background: Programmed cell death protein 1 (PD-1) or its ligand (PD-L1) monoclonal antibody combined with bevacizumab (a monoclonal antibody targeting vascular endothelial growth factor) has been established as first-line systemic treatment for advanced hepatocellular carcinoma (HCC). Radiotherapy is a crucial local treatment for HCC. Mutual efficacy enhancement has been reported between radiotherapy, anti-angiogenesis therapy and immunotherapy in preclinical researches, but not been validated in clinical practice. Whether radiotherapy can enhance efficacy of anti-PD-1 immunotherapy plus bevacizumab for HCC remains unclear. This retrospective observational study aimed to appraise efficacy and safety of the combination of radiotherapy with pembrolizumab (a PD-1 monoclonal antibody) and bevacizumab for advanced HCC for the first time. Methods: Patients with advanced HCC treated by intrahepatic tumor-directed moderately hypo-fractionated radiotherapy combined with pembrolizumab and bevacizumab were consecutively included. Clinicopathological characteristics, therapeutic outcomes and treatment-related adverse events (TRAEs) were recorded and evaluated. Results: A total of 23 patients were eventually enrolled. Median cycles of pembrolizumab and bevacizumab were 4 (median, 1-8) and 4 (median, 1-9) cycles. The objective response rates and disease control rates of irradiated intrahepatic HCC and non-irradiated extrahepatic HCC were 34.8% [95% confidence interval (CI), 16.4-57.3%] vs. 10.0% (95% CI, 1.2-31.7%), and 91.3% (95% CI, 72.0-98.9%) vs. 70.0% (95% CI, 45.7-88.1%), respectively. The median progression-free survival (PFS) and overall survival (OS) were 6.6 (95% CI, 4.7-8.5) and 18.3 (95% CI, 8.2-33.6) months, and 12-month PFS and OS rates were 17.5% (95% CI, 7.0-28.0%) and 60.9% (95% CI, 50.7-71.1%). Two patients (8.7%) with locally advanced, unresectable HCC eventually underwent curative resection of tumors after this trimodal treatment. Eighteen patients (78.3%) had ≥ grade 3 TRAEs, with myelosuppression and transaminase increase as the most common. Conclusions: This study firstly reported that combining radiotherapy with pembrolizumab and bevacizumab was preliminarily a feasible and effective therapeutic choice for advanced HCC in despite of more TRAEs. This tri-modal regimen may be a potential conversion therapy for unresectable, locally advanced HCC. The limitations of this study are its retrospective nature and small sample size; therefore, big-sample prospective studies are warranted to further investigate this tri-modal regimen.

C2orf48 promotes the progression of nasopharyngeal carcinoma by regulating high mobility group AT-hook 2.

Recurrence and metastasis are the major factors affecting the survival of nasopharyngeal carcinoma (NPC), and the mechanism remains unclear. Long non-coding RNA chromosome 2 open reading frame 48 (C2orf48) has been shown to influence the prognosis of many cancers. However, C2orf48's function in NPC has not been clarified. In this investigation, C2orf48 expression in NPC was measured by quantitative real-time PCR (qRT-PCR) at the cellular and tissue levels, and the association between C2orf48 expression and the prognosis of patients with NPC was examined. Additionally, the effects of C2orf48 and high mobility group AT-hook 2 (HMGA2) upon NPC proliferation, migration, and invasion were examined employing the MTT assay, colony formation assay, and transwell assay, respectively. Furthermore, the association between C2orf48 and HMGA2 in NPC was investigated. Our research demonstrated that C2orf48 was overexpressed in NPC tissues and cell lines, and compared to patients with lower levels of C2orf48 expression, those with higher levels had poorer 5-year overall survival and progression-free survival. Functionally, C2orf48 overexpression accelerated NPC cells proliferation, migration, and invasion. Besides, the tandem mass tag (TMT) quantitative proteomic analysis indicated that HMGA2 may be a target of C2orf48. Moreover, upregulation of C2orf48 could increase HMGA2 expression, and HMGA2 silencing could counteract the proliferation, migration, and invasion changes induced by C2orf48 in NPC cells. These results reveal that overexpression of C2orf48 can promote NPC cells proliferation, migration, and invasion via regulating the expression of HMGA2 and C2orf48 may be a potentially important prognostic marker for NPC.

Association between vaginal microbiota and the progression of ovarian cancer.

Ovarian cancers, especially high-grade serous ovarian cancer (HGSOC), are one of the most lethal age-independent gynecologic malignancies. Although pathogenic microorganisms have been demonstrated to participate in the pathogenesis of multiple types of tumors, their potential roles in the development of ovarian cancer remain unclear. To gain an insight into the microbiome-associated pathogenesis of ovarian cancer and identify potential diagnostic biomarkers, we applied different techniques to analyse the microbiome and serum metabolome of different resources. We found that the vaginal microbiota in ovarian cancer mouse models was under dysbiosis, with altered metabolite configurations that may result from amino acid or lysophospholipid metabolic processes. Local therapeutic intervention with a broad spectrum of antibiotics was effective in reversing microbiota dysbiosis and suppressing carcinogenic progression. As the ovary is situated deeply in the pelvis, it is difficult to directly monitor the ovarian microbial community. Our findings provide alternative options for utilizing the vaginal bacteria as noninvasive biomarkers, such as Burkholderia (area under the curve = 0.8843, 95% confidence interval: 0.743-1.000), which supplement the current invasive diagnostic methods for monitoring ovarian cancer progression and contribute to the development of advanced microbe-based diagnosis and adjuvant therapies.

Efficacy and safety of PLDR-IMRT for the re-irradiation of recurrent NPC: A prospective, single-arm, multicenter trial.

Salvage treatment of locoregionally recurrent nasopharyngeal carcinoma (NPC) requires weighing the benefits of re-irradiation against increased risks of toxicity. Here, we evaluated the outcomes of patients treated with intensity-modulated-based pulsed low-dose-rate radiotherapy (PLDR-IMRT) to enhance the curative effect of salvage treatment and reduce RT-related SAEs. A prospective clinical trial was conducted from March 2018 to March 2020 at multiple institutions. NPC patients who experienced relapse after radical therapy were re-irradiated with a median dose of 60 Gy (50.4-70 Gy)/30 f (28-35 f) using PLDR-IMRT. Thirty-six NPC patients who underwent PLDR-IMRT for locoregional recurrence were identified. With a median follow-up of 26.2 months, the objective response rate (ORR) of the entire cohort was 91.6%. The estimated mPFS duration was 28 months (95% CI: 24.9-31.1), and the estimated mLRFS duration was 30.4 months (95% CI: 25.2-35.5). The overall survival (OS) rate for all patients was 80.6%, the progression-free survival (PFS) rate was 75% and the cancer-specific survival (CSS) rate was 88.9% at 1 year. The LRFS and DMFS rates were 88.9% and 91.7%, respectively, at 1 year. A combination of systematic therapies could provide survival benefits to patients who experience NPC relapse (p < 0.05), and a Karnofsky performance status (KPS) score of ≥90 was a favorable factor for local control (p < 0.05). The incidence of acute SAEs (grade 3+) from PLDR was 22.2%, and the incidence of chronic SAEs was 19.4% among all patients. PLDR-IMRT combined with systematic therapy can effectively treat patients with locoregionally recurrent nasopharyngeal carcinoma and causes fewer adverse events than the rates expected with IMRT.

X-box Binding Protein 1 is a Potential Immunotherapy Target in Ovarian Cancer.

The allure of potentially dramatic and durable responses to immunotherapy has driven the study of several immune checkpoint inhibitor (ICI) agents in ovarian cancer. However, the results of ICI therapy in ovarian cancer have been rather disappointing. It is important to understand the reasons for the poor efficacy of ICI in ovarian cancer and to look for new targets for immunotherapy. To solve this problem, ovarian cancer-associated datasets were individually collected from The Cancer Genome Atlas (TCGA)、International Cancer Genome Consortium (ICGC)、Genotype-Tissue Expression (GTEx), and comprehensively performed to expression, prognostic, pathological correlation, genomic and immunologic analyses of reported all immune checkpoints by Gene Expression Profiling Interactive Analysis 2 (GEPIA2), Tumor and Immune System Interaction Database (TISIDB), cBio Cancer Genomics Portal (cBioPortal), and Kaplan-Meier Plotter. We concluded that those well-identified immune checkpoints might not be ideal targets for ovarian cancer immunotherapy. Intriguingly, the genomic alteration of X-box binding protein 1 (XBP1), the important mediator of chemotherapy-induced cancer immunogenic cell death, was found to be a potential coregulator of immune checkpoints in ovarian cancer. Importantly, XBP1 was detected to be highly expressed in ovarian cancer compared with normal ovarian tissue, and high XBP1 expression significantly benefits both overall survival (OS) and disease-free survival (DFS) of ovarian cancer patients. More importantly, XBP1 was further observed to be closely related to anti-tumor immunity in ovarian cancer, including multiple T-cell signatures and immunity-killing molecules. In conclusion, upregulating XBP1 rather than targeting immune checkpoints represents a potentially more efficient approach for ovarian cancer therapy.

Application of Convolution Neural Network Algorithm Based on Multicenter ABUS Images in Breast Lesion Detection.

Objective: This study aimed to evaluate a convolution neural network algorithm for breast lesion detection with multi-center ABUS image data developed based on ABUS image and Yolo v5. Methods: A total of 741 cases with 2,538 volume data of ABUS examinations were analyzed, which were recruited from 7 hospitals between October 2016 and December 2020. A total of 452 volume data of 413 cases were used as internal validation data, and 2,086 volume data from 328 cases were used as external validation data. There were 1,178 breast lesions in 413 patients (161 malignant and 1,017 benign) and 1,936 lesions in 328 patients (57 malignant and 1,879 benign). The efficiency and accuracy of the algorithm were analyzed in detecting lesions with different allowable false positive values and lesion sizes, and the differences were compared and analyzed, which included the various indicators in internal validation and external validation data. Results: The study found that the algorithm had high sensitivity for all categories of lesions, even when using internal or external validation data. The overall detection rate of the algorithm was as high as 78.1 and 71.2% in the internal and external validation sets, respectively. The algorithm could detect more lesions with increasing nodule size (87.4% in ≥10 mm lesions but less than 50% in <10 mm). The detection rate of BI-RADS 4/5 lesions was higher than that of BI-RADS 3 or 2 (96.5% vs 79.7% vs 74.7% internal, 95.8% vs 74.7% vs 88.4% external). Furthermore, the detection performance was better for malignant nodules than benign (98.1% vs 74.9% internal, 98.2% vs 70.4% external). Conclusions: This algorithm showed good detection efficiency in the internal and external validation sets, especially for category 4/5 lesions and malignant lesions. However, there are still some deficiencies in detecting category 2 and 3 lesions and lesions smaller than 10 mm.

Corrigendum: DDX19A Promotes Metastasis of Cervical Squamous Cell Carcinoma by Inducing NOX1-Mediated ROS Production.

[This corrects the article DOI: 10.3389/fonc.2021.629974.].

[The research progress of PD-1/L1 inhibitors application in the treatment of head and neck squamous cell carcinoma].

Over the past few years, the FDA has approved PD-1/L1 inhibitor for the treatment of advanced head and neck squamous cell carcinoma, involving PD-1/L1 inhibitor monotherapy, PD-1/L1 inhibitor combined with chemoradiotherapy, combined with targeted therapy, combined with neoadjuvant immunotherapy and duplex-block of immune checkpoints and so on. Herein, we briefly review the latest research results in this field, and summarize the application and efficacy of immunotherapy in the treatment of head and neck squamous cell carcinoma， which will benefits such patients to develop more precise and individualized treatment plans.

In the Tumor Microenvironment, ETS1 Is an Oncogenic Immune Protein: An Integrative Pancancer Analysis.

Background: Previous research suggested that ETS1 (ETS proto-oncogene 1, transcription factor) could be useful for cancer immunotherapy. The processes underlying its therapeutic potential, on the other hand, have yet to be thoroughly investigated. The purpose of this study was to look into the relationship between ETS1 expression and immunity. Methods: TCGA and GEO provide raw data on 33 different cancers as well as GSE67501, GSE78220, and IMvigor210. In addition, we looked at ETS1's genetic changes, expression patterns, and survival studies. The linkages between ETS1 and TME, as well as its association with immunological processes/elements and the major histocompatibility complex, were explored to effectively understand the role of ETS1 in cancer immunotherapy. Three distinct immunotherapeutic cohorts were employed to examine the relationship between ETS1 and immunotherapeutic response. Results: ETS1 expression was shown to be high in tumor tissue. ETS1 overexpression is linked to a worse clinical outcome in individuals with overall survival. Immune cell infiltration, immunological modulators, and immunotherapeutic signs are all linked to ETS1. Overexpression of ETS1 is linked to immune-related pathways. However, no statistically significant link was found between ETS1 and immunotherapeutic response. Conclusions: ETS1 may be a reliable biomarker for tumor prognosis and a viable prospective therapeutic target for human cancer immunotherapy (e.g., KIRP, MESO, BLCA, KIRC, and THYM).

Protective Effects of Ulva lactuca Polysaccharide Extract on Oxidative Stress and Kidney Injury Induced by D-Galactose in Mice.

Reactive oxygen species (ROS) are the key factors that cause many diseases in the human body. Polysaccharides from seaweed have been shown to have significant antioxidant activity both in vivo and in vitro. The ameliorative effect of Ulva lactuca polysaccharide extract (UPE) on renal injury induced by oxidative stress was analyzed. As shown by hematoxylin-eosin staining results, UPE can significantly improve the kidney injury induced by D-galactose (D-gal). Additionally, the protective mechanism of UPE on the kidney was explored. The results showed that UPE could decrease the levels of serum creatinine (Scr), blood urea nitrogen (BUN), serum cystatin C (Cys-C), lipid peroxidation, protein carbonylation, and DNA oxidative damage (8-OHdG) and improve kidney glutathione content. Moreover, UPE significantly increased the activities of superoxide dismutase and glutathione peroxidase and total antioxidant activity in mice. UPE also decreased the levels of inflammatory cytokines TNF-α and IL-6. Further investigation into the expression of apoptotic protein caspase-3 showed that UPE decreased the expression of apoptotic protein caspase-3. These results indicate that UPE has a potential therapeutic effect on renal injury caused by oxidative stress, providing a new theoretical basis for the treatment of oxidative damage diseases in the future.

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.

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.

Correlation Analysis Between MTHFR C677T Polymorphism and Uterine Fibroids: A Retrospective Cohort Study.

BACKGROUND: Uterine fibroids(UF) are the most common benign tumors in women, with high incidence and unknown causes. We aimed to explore the correlation between Methylenetetra-hydrofolate reductase (MTHFR) C677T polymorphism and UF. METHODS: This is a retrospective cohort study. Data were collected from 2411 women detected for MTHFR C677T polymorphism in the Fifth Affiliated Hospital of Sun Yat-sen University from 2018 to 2020. B-ultrasound (BU) and the first page of medical records were used to analyze whether they had ever been diagnosed with UF. The collected data were analyzed. Using the chi-square test and regression analysis to explore the correlation, and the risk factors was screened by multifactor logistic regression analysis. RESULTS: A total of 2411 pregnant women were in the MTHFR C677T polymorphism detection. Among them, 226(9.37%) were diagnosed as UF by BU or clinical diagnosis. The allele and genotype of MTHFR C677T were significantly different between the case and control group (p<0.05), and the distribution of the allele was following Hardy-Weinberg (H-W) equilibrium. Comparing with the wild-type (C/C), the mutant group (C/T+T/T) was more likely to form UF(OR,1.43;OR95%CI,1.07-1.89). After adjusting for confoundings, the heterozygous mutant (C/T) was more susceptible to UF than the wild-type (aOR,1.41;aOR95%CI,1.41-1.91). In the case group, BMI, gravidity and parity were not associated with the size and number of UF and the MTHFR C677T polymorphism (p>0.05). However, older maternal age was associated with the incidence of UF, especially the multiple UF (p<0.05). CONCLUSION: Our results found that MTHFR C677T polymorphism was associated with UF occurrence for the first time. This could imply that it may increase the risk of forming UF in women of gestational age.

DDX19A Promotes Metastasis of Cervical Squamous Cell Carcinoma by Inducing NOX1-Mediated ROS Production.

The major obstacle to treat cervical squamous cell carcinoma (CSCC) is the high prevalence of metastasis, which severely affects 5-year survival rate and quality of life for cancer patients. The DEAD-box helicase family has been reported to be a critical mediator in the development and metastasis of various cancers. DEAD-box helicase 19A (DDX19A) is a member of the DEAD-box helicase family; however, its functional role in CSCC is unclear. In this study, bioinformatics analysis of clinical samples from public databases demonstrated that the expression of DDX19A was elevated in CSCC tissues and that high expression of DDX19A was positively correlated with metastasis and poor clinical outcome. Functionally, we found that DDX19A promoted CSCC cell migration and invasion in vitro and lung metastasis in vivo. Mechanistically, overexpression of DDX19A increased NADPH oxidase 1 (NOX1) expression, enhanced reactive oxygen species (ROS) production, and induced the migration and invasion of CSCC cells. Rescue experiments revealed that DDX19A-induced CSCC functional alterations were dependent on NOX1 and that DDX19A-promoted CSCC metastasis was abrogated upon the inhibition of ROS. Our results demonstrated that DDX19A could promote CSCC metastasis by inducing NOX1-mediated ROS production and that blockage of the NOX1/ROS axis might serve as a potential therapeutic target for patients with DDX19A-overexpressed CSCC.

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.

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.

Prognostic value of prostaglandin I2 synthase and its correlation with tumor-infiltrating immune cells in lung cancer, ovarian cancer, and gastric cancer.

BACKGROUND: Prostaglandin I2 synthase (PTGIS) is a crucial gene for the synthesis of prostaglandin I2, which has multiple roles in inflammation and immune modulation. However, studies on the prognostic value of PTGIS and its correlation with tumor-infiltrating immune cells in multiple cancers are still rare. RESULTS: Multiple datasets of the Oncomine database showed that PTGIS was expressed at low levels in lung cancer and ovarian cancer compared to the levels in normal tissues. Kaplan-Meier plotter showed that high PTGIS was associated with poor overall survival and progression-free survival in lung, ovarian, and gastric cancers. Moreover, PTGIS expression was significantly positively correlated with infiltrating levels of macrophages and was strongly associated with a variety of immune markers, especially tumor-associated macrophages (TAMs) and T-regulatory cells (Tregs). CONCLUSIONS: High expression of PTGIS could promote the infiltration of TAMs and Tregs in the tumor microenvironment and deteriorate outcomes of patients with lung, ovarian, and gastric cancers. These findings suggest that PTGIS could be taken as a potential biomarker of prognosis and tumor-infiltrating immune cells. METHODS: PTGIS expression was investigated in different datasets of the Oncomine database, and its expression levels in various tumors and corresponding normal tissues were analyzed by the Tumor Immune Estimation Resource (TIMER). Then, the clinical prognostic value of PTGIS was assessed with online public databases. In addition, we initially explored the correlation between PTGIS and tumor-infiltrating immune cells by TIMER and Gene Expression Profiling Interactive Analysis (GEPIA).