Analysis of Related Factors of Tumor Recurrence or Progression After Transnasal Sphenoidal Surgical Treatment of Large and Giant Pituitary Adenomas and Establish a Nomogram to Predict Tumor Prognosis

BackgroundPituitary adenoma (PA) is a benign neuroendocrine tumor caused by adenohypophysial cells, and accounts for 10%-20% of all primary intracranial tumors. The surgical outcomes and prognosis of giant pituitary adenomas measuring ≥3 cm in diameter differ significantly due to the influence of multiple factors such as tumor morphology, invasion site, pathological characteristics and so on. The aim of this study was to explore the risk factors related to the recurrence or progression of giant and large PAs after transnasal sphenoidal surgery, and develop a predictive model for tumor prognosis.MethodsThe clinical and follow-up data of 172 patients with large or giant PA who underwent sphenoidal surgery at the Second Affiliated Hospital of Zhejiang University School of Medicine from January 2011 to December 2017 were retrospectively analyzed. The basic clinical information (age, gender, past medical history etc.), imaging features (tumor size, invasion characteristics, extent of resection etc.), and histopathological characteristics (pathological results, Ki-67, P53 etc.) were retrieved. SPSS 21.0 software was used for statistical analysis, and the R software was used to establish the predictive nomogram.ResultsSeventy out of the 172 examined cases (40.7%) had tumor recurrence or progression. The overall progress free survival (PFS) rates of the patients at 1, 3 and 5 years after surgery were 90.70%, 79.65% and 59.30% respectively. Log-rank test indicated that BMI (P < 0.001), Knosp classification (P < 0.001), extent of resection (P < 0.001), Ki-67 (P < 0.001), sphenoidal sinus invasion (P = 0.001), Hardy classification (P = 0.003) and smoking history (P = 0.018) were significantly associated with post-surgery recurrence or progression. Cox regression analysis further indicated that smoking history, BMI ≥25 kg/m2, Knosp classification grade 4, partial resection and ≥3% Ki-67 positive rate were independent risk factors of tumor recurrence or progression (P < 0.05). In addition, the nomogram and ROC curve based on the above results indicated significant clinical value.ConclusionThe postoperative recurrence or progression of large and giant PAs is related to multiple factors and a prognostic nomogram based on BMI (≥25 kg/m2), Knosp classification (grade 4), extent of resection (partial resection) and Ki-67 (≥3%) can predict the recurrence or progression of large and giant PAs after transnasal sphenoidal surgery.

Identification of Gene-Set Signature in Early-Stage Hepatocellular Carcinoma and Relevant Immune Characteristics

BackgroundThe incidence of hepatocellular carcinoma (HCC) is rising worldwide, and there is limited therapeutic efficacy due to tumor microenvironment heterogeneity and difficulty in early-stage screening. This study aimed to develop and validate a gene set-based signature for early-stage HCC (eHCC) patients and further explored specific marker dysregulation mechanisms as well as immune characteristics.MethodsWe performed an integrated bioinformatics analysis of genomic, transcriptomic, and clinical data with three independent cohorts. We systematically reviewed the crosstalk between specific genes, tumor prognosis, immune characteristics, and biological function in the different pathological stage samples. Univariate and multivariate survival analyses were performed in The Cancer Genome Atlas (TCGA) patients with survival data. Diethylnitrosamine (DEN)-induced HCC in Wistar rats was employed to verify the reliability of the predictions.ResultsWe identified a Cluster gene that potentially segregates patients with eHCC from non-tumor, through integrated analysis of expression, overall survival, immune cell characteristics, and biology function landscapes. Immune infiltration analysis showed that lower infiltration of specific immune cells may be responsible for significantly worse prognosis in HCC (hazard ratio, 1.691; 95% CI: 1.171–2.441; p = 0.012), such as CD8 Tem and cytotoxic T cells (CTLs) in eHCC. Our results identified that Cluster C1 signature presented a high accuracy in predicting CD8 Tem and CTL immune cells (receiver operating characteristic (ROC) = 0.647) and cancerization (ROC = 0.946) in liver. As a central member of Cluster C1, overexpressed PRKDC was associated with the higher genetic alteration in eHCC than advanced-stage HCC (aHCC), which was also connected to immune cell-related poor prognosis. Finally, the predictive outcome of Cluster C1 and PRKDC alteration in DEN-induced eHCC rats was also confirmed.ConclusionsAs a tumor prognosis-relevant gene set-based signature, Cluster C1 showed an effective approach to predict cancerization of eHCC and its related immune characteristics with considerable clinical value.

Immune Infiltration of MMP14 in Pan Cancer and Its Prognostic Effect on Tumors

BackgroundMatrix metalloproteinase 14 (MMP14) is a member of the MMP family, which interacts with tissue inhibitors of metalloproteinase (TIMPs), and is involved in normal physiological functions such as cell migration, invasion, metastasis, angiogenesis, and proliferation, as well as tumor genesis and progression. However, there has been a lack of relevant reports on the effect of MMP14 across cancers. This study aims to explore the correlation between MMP14 and pan-cancer prognosis, immune infiltration, and the effects of pan-cancer gene mismatch repair (MMR), microsatellite instability (MSI), tumor mutational burden (TMB), DNA methylation, and immune checkpoint genes.MethodsIn this study, we used bioinformatics to analyze data from multiple databases, including The Cancer Genome Atlas (TCGA), ONCOMINE, and Kaplan–Meier plotter. We investigated the relationship between the expression of MMP14 in tumors and tumor prognosis, the relationship between MMP14 expression and tumor cell immune infiltration, and the relationship between MMR gene MMR, MSI, TMB, DNA methylation, and immune checkpoint genes.ResultsMMP14 expression is highly associated with the prognosis of a variety of cancers and tumor immune invasion and has important effects on pan oncologic MMR, MSI, TMB, DNA methylation, and immune checkpoint genes.ConclusionMMP14 is highly correlated with tumor prognosis and immune invasion and affects the occurrence and progression of many tumors. All of these results fully indicate that MMP14 may be a biomarker for the prognosis, diagnosis, and treatment of many tumors and provide new ideas and direction for subsequent tumor immune research and treatment strategies.

A 20-Year Research Trend Analysis of the Influence of Anesthesia on Tumor Prognosis Using Bibliometric Methods

BackgroundBibliometric analysis is used to gain a systematic understanding of developments in the field of the influence of anesthesia on tumor prognosis and changes in research hot spots over the past 20 years.MethodsRelevant publications from the Web of Science Core Collection (WoSCC) were downloaded on May 5, 2021. Acquired data were then analyzed using the Online Analysis Platform of Literature Metrology (http://biblimetric.com) and the CiteSpace software was used to analyze and predict trends and hot spots in this field.Results1,521 publications on the influence of anesthesia on tumor prognosis were identified and 1494 qualifying records were included in the final analysis. The leading country in this field was the United States of America (USA). The University of Texas MD Anderson Cancer Center (Houston, TX, USA) and Pennsylvania State University (State College, PA, USA) featured the highest number of publications among all institutions. Co-citation cluster labels revealed characteristics of ten main clusters: total intravenous anesthesia, opioid growth factor receptor, gastric cancer cell, opioid receptor, murine model, natural killer cell activity, health-related quality, glioma cell, opioid switching and mu-type opioid receptor. Keyword burst detection indicated that randomized controlled trials (RCTs), volatile anesthetics, and ropivacaine were the newly emerging research hot spots.ConclusionsThis study compiled 1494 publications covering anesthesia and tumor prognosis research and showed that the direction of these studies is likely in transition from opioids and their receptors to other anesthetics, and from retrospective studies to prospective randomized controlled trials. It provides guidance for further research and clinical applications on choosing anesthetic methods and drugs.

Immune infiltration of MMP14 in Pan-cancer and its prognostic effect on tumor

Background: Matrix metallopeptidase 14(MMPL4) is a member of the matrix metalloproteinase family, which interacts with tissue metalloproteinase inhibitors (TIMPs), and is involved in normal physiological functions such as cell migration, invasion, metastasis, angiogenesis and proliferation, as well as tumor genesis and progression. However, there has been a lack of relevant reports on the effect of MMP14 on pan-cancer. This study aims to explore the correlation between MMP14 and pan-cancer prognosis, immune infiltration, and the effects of pan-cancer gene mismatch repair (MMR), microsatellite instability (MSI), tumor mutation load (TMB), DNA methylation, and immune checkpoint genes.Methods: In this study, we used bioinformatics to analyze data from multiple databases, including TCGA, Oncomine and Kaplan-Meier Plotter. We investigated the relationship between the expression of MMP14 in tumors and tumor prognosis, the relationship between MMP14 expression and tumor cell immune infiltration, and the relationship between MMR gene mismatch repair (MMR), microsatellite instability (MSI), tumor mutation load (TMB), DNA methylation, and immune checkpoint genes.Results: MMP14 expression is highly associated with prognosis of a variety of cancers, tumor immunoinvasion, and has important effects on pan-oncologic mismatch repair (MMR), microsatellite instability (MSI), tumor mutation load (TMB), DNA methylation, and immune checkpoint genes. Conclusion: MMP14 is highly correlated with tumor prognosis and immunoinvasion, and affects the occurrence and progression of many tumors. All these fully indicate that MMP14 may be a biomarker for the prognosis, diagnosis and treatment of many tumors, and provide a new idea and direction for subsequent tumor immune research and treatment strategies.

Targeting Ubiquitin-Specific Protease 7 (USP7) in Cancer: A New Insight to Overcome Drug Resistance

Chemoresistance is one of the leading causes for the failure of tumor treatment. Hence, it is necessary to study further and understand the potential mechanisms of tumor resistance to design and develop novel anti-tumor drugs. Post-translational modifications are critical for proteins’ function under physiological and pathological conditions, among which ubiquitination is the most common one. The protein degradation process mediated by the ubiquitin-proteasome system is the most well-known function of ubiquitination modification. However, ubiquitination also participates in the regulation of many other biological processes, such as protein trafficking and protein-protein interaction. A group of proteins named deubiquitinases can hydrolyze the isopeptide bond and disassemble the ubiquitin-protein conjugates, thus preventing substrate proteins form degradation or other outcomes. Ubiquitin-specific protease 7 (USP7) is one of the most extensively studied deubiquitinases. USP7 exhibits a high expression signature in various malignant tumors, and increased USP7 expression often indicates the poor tumor prognosis, suggesting that USP7 is a marker of tumor prognosis and a potential drug target for anti-tumor therapy. In this review, we first discussed the structure and function of USP7. Further, we summarized the underlying mechanisms by which tumor cells develop resistance to anti-tumor therapies, provided theoretical support for targeting USP7 to overcome drug resistance, and some inspiration for the design and development of USP7 inhibitors.

Integrative Analysis of Complement System to Prognosis and Immune Infiltrating in Colon Cancer and Gastric Cancer

BackgroundThe complement system acts as an integral part of the innate immune response, which acts primarily to remove pathogens and injured cells. Emerging evidence has shown the activation of the immune regulatory function of complements in the tumor microenvironment (TME). We revealed the expression levels of various complements in human cancers and their role in tumor prognosis and immune infiltration.MethodsThe differential expression of complements was explored via the Tumor Immune Estimation Resource (TIMER) site and the Oncomine database. To investigate whether these differentially expressed complements have correlation with the prognosis of gastric cancer (GC) and colon cancer, their impact on survival was assessed using the PrognoScan database and Kaplan-Meier plotter. The correlations between complements and tumor immune-infiltrating levels and immune gene markers were statistically explored in TIMER based on Spearman’s correlation coefficients and p-values.ResultsIn two colon cancer cohorts, an increased expression level of DAF (CD55) has statistically significant correlation with poor disease-free survival (DFS). High C3, CR4, and C5aR1 expression levels were significantly related with poor prognosis in GC patients. In addition, C3, CR4, and C5aR1 expression was positively related to the tumor purity and infiltration levels of multiple immune cells in stomach adenocarcinoma (STAD). Moreover, the expression levels of C3, CR4, and C5aR1 were also strongly correlated with various immune marker sets, such as those of tumor-associated macrophages (TAMs), M1 and M2 macrophages, T cell exhaustion, Tregs, and DCs, in STAD. Additionally, CD55 has positive correlation with few immune cell infiltration levels in colon adenocarcinoma (COAD), but its correlation with immune marker sets was not statistically significant.ConclusionThese findings confirm the relationship between various complements and tumor prognosis and immune infiltration in colon cancer and GC. CD55 may serve as an indicator on the survival prognosis of patients with colon cancer. Furthermore, as biomarkers for poor prognosis in GC, complements C3, CR4, and C5aR1 may provide potential biological targets for GC immunotherapy.

Simple and fast isolation of circulating exosomes with chitosan modified shuttle flow microchip towards breast cancer diagnosis

Tumor-derived exosomes have been recognized as promising biomarkers for early-stage cancer diagnosis, tumor prognosis monitoring and individual medical treatment. However, separating exosomes from trace biological samples is a huge challenge...