ATF1 promotes the malignancy of lung adenocarcinoma cells by transcriptionally regulating ZNF143 expression.

The clinical oncogenic functions and mechanisms of activating transcription factor 1 (ATF1) in the progression of lung adenocarcinoma have not been completely elucidated. In this study, by employing human lung adenocarcinoma tissues and cells, we detect the correlation of ATF1 expression with the clinicopathological features and prognosis of patients with lung adenocarcinoma and find that ATF1 promotes lung adenocarcinoma cell proliferation and migration by transcriptionally enhancing zinc finger protein 143 (ZNF143) expression. ATF1 and ZNF143 are strongly expressed in lung adenocarcinoma tissues compared with those in the adjacent normal tissues, and high ATF1 and ZNF143 expressions are related to poor disease-free survival of lung adenocarcinoma patients. ATF1 overexpression results in increased proliferation and migration of lung adenocarcinoma cells, whereas knockdown of ATF1 inhibits cell proliferation and migration. Furthermore, ATF1 transcriptionally regulates the expression of ZNF143, and ATF1 and ZNF143 expressions are positively correlated in lung adenocarcinoma tissues. ZNF143 knockdown blocks lung adenocarcinoma cell migration, which is mediated by ATF1 upregulation. Hence, this study provides a potential therapeutic candidate for the treatment of lung adenocarcinoma.

Contrast-Enhanced Ultrasound Differentiation Between Low- and High- Grade Bladder Urothelial Carcinoma and Correlation With Tumor Microvessel Density.

OBJECTIVES: Time-intensity curves (TICs) of contrast-enhanced ultrasound (CEUS) were analyzed retrospectively to differentiate between low-grade and high-grade bladder urothelial carcinoma, and to investigate correlation with tumor microvessel density (MVD). METHODS: The data of 105 patients with pathologically confirmed bladder urothelial carcinoma (55 low-grade and 50 high-grade) were reviewed. Lesions were examined before surgery using conventional ultrasound and CEUS with TIC analysis. The TIC parameters time from peak to one-half the signal intensity (TPH) and the corresponding descending slope (DS) of the low-grade and high-grade groups were compared, and receiver operating characteristic curves constructed. The MVDs of the resectioned tissue specimens were quantified via immunohistochemistry for CD34. RESULTS: Based on conventional ultrasound, the low-grade and high-grade groups were similar in tumor shape, number, topography, internal echo, height, width, and vascularity. The TPH of the high-grade group was significantly longer than that of the low-grade group, and the DS was lower. The cutoff points of TPH and DS for differentiating low-grade and high-grade bladder urothelial carcinoma were 48.06 seconds and 0.15 dB/seconds, respectively (area under the receiver operating characteristic curve = 0.79 for both). The mean MVDs per high-power field of the low-grade and high-grade groups were 41.39 16.65 and 51.03 20.16, respectively (P = .009). The TPH correlated linearly with MVD (P < .01), as did the DS (P < .01). CONCLUSIONS: Contrast-enhanced ultrasound can be used to differentiate low from high-grade bladder urothelial carcinoma. The TIC parameters of CEUS reflect the MVD of bladder urothelial tumors and may be helpful for evaluating tumor angiogenesis, with implications for clinical diagnosis, treatment, and prognosis.

Prognostic biomarker HIF1α and its correlation with immune infiltration in gliomas.

Certain glioma subtypes, such as glioblastoma multiforme or low-grade glioma, are common malignant intracranial tumors with high rates of relapse and malignant progression even after standard therapy. The overall survival (OS) is poor in patients with gliomas; hence, effective prognostic prediction is crucial. Herein, the present study aimed to explore the potential role of hypoxia-inducible factor 1 subunit alpha (HIF1α) in gliomas and investigate the association between HIF1α and infiltrating immune cells in gliomas. Data from The Cancer Genome Atlas were evaluated via RNA sequencing, clinicopathological, immunological checkpoint, immune infiltration and functional enrichment analyses. Validation of protein abundance was performed using paraffin-embedded samples from patients with glioma. A nomogram model was created to forecast the OS rates at 1, 3 and 5 years after cancer diagnosis. The association between OS and HIF1α expression was estimated using Kaplan-Meier survival analysis and the log-rank test. Finally, HIF1α expression was validated using western blotting, reverse transcription-quantitative PCR, Cell Counting Kit-8 and Transwell assays. The results demonstrated that HIF1α expression was significantly upregulated in gliomas compared with normal human brain glial cells. Immunohistochemistry staining demonstrated differential expression of the HIF1α protein. Moreover, glioma cell viability and migration were inhibited via HIF1α downregulation. HIF1α impacted DNA replication, cell cycling, DNA repair and the immune microenvironment in glioma. HIF1α expression was also positively associated with several types of immune cells and immunological checkpoints and with neutrophils, plasmacytoid dendritic cells and CD56bright cells. The Kaplan-Meier survival analyses further demonstrated a strong association between high HIF1α expression and poor prognosis in patients with glioma. Analysis of the receiver operating characteristic curves demonstrated that HIF1α expression accurately differentiated paired normal brain cells from tumor tissues. Collectively, these findings suggested the potential for HIF1α to be used as a novel prognostic indicator for patients with glioma and that OS prediction models may help in the future to develop effective follow-up and treatment strategies for these patients.

DPP7 as a Potential Therapeutic Marker for Colorectal Cancer.

Background: Dipeptidyl peptidase 7 (DPP7) is overexpressed in various tumors, but its role in colorectal cancer (CRC) remains unclear. Study the Impact of DPP7 on malignant progression and tumor immunity in CRC. Methods: We utilized Tumor Immune Estimation Resource 2.0 (TIMER2.0) and The Cancer Genome Atlas (TCGA) analyses to assess the expression of DPP7 in tumors and validated it through immunohistochemistry and immunoblotting. Additionally, we investigated the relationship between DPP7 and immune cell infiltration using single-sample Gene Set Enrichment Analysis (ssGSEA) analysis. Finally, the impact of DPP7 on cell proliferation, invasion, migration, and immune cell function in the tumor microenvironment was confirmed through cell experiments and animal studies. Results: DPP7 is highly expressed in CRC, and high expression of DPP7 is associated with poor prognosis. Cell experiments demonstrate that overexpression of DPP7 enhances the proliferation, migration, and invasion capabilities of colorectal cancer cells both in vitro and in vivo. Immune infiltration analysis and co-culture results indicate that overexpression of DPP7 suppresses the immune cell's cytotoxic function against tumors in the tumor microenvironment. Conclusions: DPP7 promotes the malignant potential of colorectal cancer cells and inhibits tumor immune function, thereby promoting the progression of colorectal cancer.

KRT80 Promotes Lung Adenocarcinoma Progression and Serves as a Substrate for VCP.

Background: Keratin 80(KRT80) encodes a type II intermediate filament protein, known for maintaining cell integrity of cells and its involvement in the tumorigenesis and progression of various cancers. However, comprehensive research on its relevance to lung adenocarcinoma remains limited. Methods: In this study, we utilized multiple databases to investigate the transcriptional expression of KRT80 and its correlation with clinicopathological features. A range of assays, including the Cell Counting Kit 8 assay, colony formation assay, cell migration assay, and flow cytometry, were employed to elucidate the impact of KRT80 on the malignant behavior of lung adenocarcinoma. Immunoprecipitation and mass spectrometry were also used to identify putative genes interacting with KRT80. Results: The expression of KRT80 was elevated in lung adenocarcinoma and patients with high levels of KRT80 expression had poor clinical outcomes. Silencing KRT80 suppressed cell viability, and migration, while overexpression had the opposite effect. In addition, Immunoprecipitation and mass spectrometry revealed an interaction between KRT80 and valosin-containing protein (VCP), with VCP knockdown reducing the stability of KRT80 protein. Overexpression of KRT80 mitigated the inhibitory effect of VCP knockdown to some extent. Conclusion: Our findings collectively suggest that KRT80 is a promising diagnostic and prognostic indicator for lung adenocarcinoma. Additionally, the interaction between KRT80 and VCP plays a crucial role in the progression of lung adenocarcinoma, which implies that KRT80 is a promising therapeutic target.

[Diagnostic implications of atypical squamous cells of unknown significance with abnormal DNA ploidy for early cervical lesions].

OBJECTIVE: To investigate the clinical significance of atypical squamous cells of unknown significance (ASCUS) with abnormal DNA ploidy in the early diagnosis of cervical lesions. METHODS: Eight thousand four hundred and forty-eight patients were included in this study and all had DNA quantitative analysis and cervical liquid-based cytology. Among 1041 cases with DNA aneuploidy and/or abnormal cervical liquid-based cytology and additional cervical biopsy, histological review was performed in 247 ASCUS cases with abnormal DNA ploidy. RESULTS: (1) Among 8448 cases, 7877 were normal or benign, 426 were ASCUS, 45 were ASC-H, 55 were LSIL and 22 were HSIL by TBS diagnosis. The presence of 1-2 abnormal DNA ploidy cells was detected in 15.3% (65/426) of ASCUS, 11.1% (5/45) of ASC-H, 9.1% (5/55) of LSIL, and 0 (0/22) of HSIL. The presence of ≥ 3 abnormal DNA ploidy cells was detected in 39.0% (166/426) of ASCUS, 75.6% (34/45) of ASC-H, 76.4% (42/55) of LSIL, and 95.5% (21/22) of HSIL. (2) A total of 67 cases of CIN 2, CIN 3 or cancers were found in 247 patients with ASCUS by colposcopy biopsies, of which 13.9% (5/36) had 1-2 abnormal DNA ploidy cells, 45.5% (56/123) had ≥ 3 abnormal DNA ploidy cells and 6.8% (6/88) had normal DNA polidy. ASCUS with 1-2 abnormal DNA ploidy cells and with ≥ 3 abnormal DNA ploidy cells were compared. The difference was statistically significant (χ(2) = 11.79, P < 0.01). But the difference between ASCUS with 1-2 abnormal DNA ploidy cells and normal DNA ploidy had no statistical significance (P > 0.05). CONCLUSIONS: ASCUS with ≥ 3 abnormal DNA ploidy cells has higher risk for developing CIN 2, CIN 3 or invasive carcinoma. The application of DNA quantitative analysis and cervical liquid-based cytology test can help in guiding clinical follow-up and treatment options in patients with ASCUS.

A risk model constructed using 14 N6-methyladenosine-related lncRNAs as a new prognostic marker that correlates with the immunomodulatory effect and drug sensitivity in colorectal cancer.

Background: Colorectal cancer (CRC) remains the most common gastrointestinal malignancy. Despite multimodal therapy, its mortality is high due to recurrence and metastasis. This study developed and verified a risk model consisting of 14 N6-methyladenosine (m6A) long noncoding RNAs (lncRNAs) to assess the prognosis of patients with CRC and investigated its relevance to immune regulation and drug sensitivity. Methods: The gene expression profiles and clinical data of 446 patients with CRC were retrieved from The Cancer Genome Atlas (TCGA). 14 lncRNAs were screened using the Gene Co-expression Network (corFilter =0.5, P<0.001), and univariate and least absolute shrinkage and selection operator (LASSO) Cox regression analysis to construct the optimal risk model. The predictive performance and clinical applicability of the model were next verified. In addition, we performed Gene Ontology (GO) enrichment analysis to identify potential biological functions and detected the difference in tumor mutational burden (TMB), immune function, and sensitivity to immunotherapy and other drugs between the high- and low-risk groups to evaluate the application of the constructed risk model in depth. Results: The model was found to be an appropriate marker for predicting the prognosis of patients with CRC, independent of other clinical features, and demonstrated good precision and broad clinical applicability. It correlated with pathways in the development of cancer and immune-related functions, and patients in the high-risk group had higher tumor immune dysfunction and escape (TIDE) scores. Furthermore, we found significant differences in the overall survival (OS) between patients in the high- and low-tumor mutation burden (TMB) groups, which may work in conjunction with the constructed model to better predict patients' prognosis. Finally, we identified 12 drugs, including A-443654 and sorafenib, with lower half maximal inhibitory concentration (IC50) values in the high-risk group. Conversely, 21 drugs, including gemcitabine and rapamycin, had lower IC50 values in the low-risk group. Conclusions: We constructed a risk model based on 14 m6A-related lncRNAs that could predict the prognosis of patients with CRC and provided additional therapeutic ideas for their treatment. These findings may additionally serve as a foundation for further studies on regulating CRC via m6A-related lncRNAs.

Integrative analysis identifies AKAP8L as an immunological and prognostic biomarker of pan-cancer.

A-kinase anchoring protein 8L (AKAP8L) belong to the A-kinase anchoring protein (AKAP) family. Recent studies have proved that AKAP8L is associated with the progression of various tumors. To establish a more complete understanding of the significance of AKAP8L across various types of cancers, we conducted a detailed analysis of multiple histological datasets, including the level of gene expression in pancancer, biological function, molecular characteristics, as well as the diagnostic and prognostic value of AKAP8L in pancancer. Furthermore, we focused on renal clear cell carcinoma (KIRC), and of explored the correlation of AKAP8L with clinical characteristics, prognosis of distinct patient subsets, co-expression genes and differentially expressed genes (DEG). We also performed the immunohistochemical staining and semi-quantitative verification of the monoclonal antibody established by AKAP8L. Our findings indicate that AKAP8L expression varied significantly not only across most cancer types, but also across different cancer molecules and immune subtypes. In addition, the robust ability to accurately predict cancer and its strong correlation with the prognosis of cancer strongly suggest that AKAP8L may be a potential biomarker for cancer diagnosis and prognosis. Furthermore, the high expression levels of AKAP8L were related to the worse overall survival (OS), disease-specific survival (DSS) as well as progression-free interval (PFI) of KIRC with statistical significance, especially among distinct clinical subgroups of KIRC. To sum up, AKAP8L has the potential to serve as a critical molecular biomarker for the diagnosis and prognosis of pancancer, an independent prognostic risk factor of KIRC, and a novel molecular target for cancer therapies.

Identification and validation of novel prognostic biomarkers and therapeutic targets for non-small cell lung cancer.

Background: Despite the significant survival benefits of anti-PD-1/PD-L1 immunotherapy, non-small cell lung cancer (NSCLC) remains one of the most common tumors and major causes of cancer-related deaths worldwide. Thus, there is an urgent need to identify new therapeutic targets for this refractory disease. Methods: In this study, microarray datasets GSE27262, GSE75037, GSE102287, and GSE21933 were integrated by Venn diagram. We performed functional clustering and pathway enrichment analyses using R. Through the STRING database and Cytoscape, we conducted protein-protein interaction (PPI) network analysis and identified the key genes, which were verified by the GEPIA2 and UALCAN portal. Validation of actin-binding protein anillin (ANLN) was performed by quantitative real-time polymerase chain reaction and Western blotting. Additionally, Kaplan-Meier methods were used to compute the survival analyses. Results: In total, 126 differentially expressed genes were identified, which were enriched in mitotic nuclear division, mitotic cell cycle G2/M transition, vasculogenesis, spindle, and peroxisome proliferator-activated receptor signaling pathway. 12 central node genes were identified in the PPI network complex. The survival analysis revealed that high transcriptional levels were associated with inferior survival in NSCLC patients. The clinical implication of ANLN was further explored; its protein expression showed a gradually increasing trend from grade I to III. Conclusion: These Key genes may be involved in the carcinogenesis and progression of NSCLC, which may serve as useful targets for NSCLC diagnosis and treatment.

Clinical Analysis of 50 Cases of Primary Pulmonary Lymphoma: A Retrospective Study and Literature Review.

Objective: This study aimed at to raise the awareness understanding of primary pulmonary lymphoma (PPL) by analyzing the clinical manifestation, imaging, pathology, diagnosis, treatment, and prognostic features of 50 cases of PPL. Methods: The study of 50 individuals with PPL diagnosed at the First affiliated hospital of Nanchang university between January 2009 and December 2019 was performed. Results: Overall, 27 males and 23 females were enrolled, with an average age of 57.6 ± 15.6 years. The primary symptoms included, cough (n = 37), expectoration (n = 25), sputum with blood (n = 12), and chest pain (n = 12). Two individuals had Hodgkin's lymphoma and 48 patients had non-Hodgkin's lymphoma (NHL). We divided the NHL cases into mucosa-associated lymphoid tissue lymphoma (MALT) (n = 21), diffuse large B-cell lymphoma (n = 12), small lymphocytic lymphoma (n = 2), mantle B-cell lymphoma (n = 2), follicular lymphoma (n = 1), B-cell lymphoma without further classification (n = 8), and T-cell lymphoma (n = 2). The imaging findings revealed that unilateral lung involvement was more common among the patients. The longest follow-up duration up to December 2019 was 123 months with 40 surviving patients. The 5-year overall survival and progression-free survival were 46.7% and 44.4%, respectively. Age was an independent predictive factor for the 5-year survival (hazard ratio, 8.900; P = .038), (P < .05). Conclusion: PPL is a uncommon disease with atypical clinical manifestations and is often misdiagnosed. Immunohistochemistry is currently the standard used in pathologic evaluation of PPL. MALT prognosis is better in contrast with other kinds of PPL. Surgery or radiotherapy can be considered in patients with limited lesions, and chemotherapy is the first treatment option for diffuse lesions. Age of ≥ 60 years was reported as an independent adverse predictive factor.

Comparison of Dural Graft Types and Graft Fixation Methods in Chiari Malformation Type I Decompression Surgery.

OBJECTIVE: Suboccipital decompression with duraplasty is being increasingly accepted for treating patients with Chiari malformation type I (CM-1). To date, the optimal duraplasty for CM-I has not been delineated. This study aims to compare the clinical and radiologic effects of duraplasty performed using 2 types of grafts and 2 graft fixation methods in 3 combinations. METHODS: In this retrospective study, 84 consecutive decompressions with duraplasty were analyzed. Two types of grafts (nonautologous [Non-Auto G], 90.5% and autologous [Auto G], 9.5%) and 2 graft fixations (suturing [S], 31.0%; and suturing plus gluing [S + G], 69.0%) were used in 3 different combinations: Non-Auto G S: 31.0%; Non-Auto G S + G: 59.5%, and Auto G S + G: 9.5%. All patients were followed up for 3 months. Clinical results were evaluated using the Gestalt scale, and syringomyelia results were evaluated using magnetic resonance imaging. RESULTS: According to the Gestalt scale, 82.1% of the patients showed improvement 3 months post operation, and the improvement was not related to the type of graft (P = 0.90), fixation (P = 0.90), or duraplasty (P = 0.81). Decreased syringomyelia was observed in 76.4% of the patients. It was not associated with the graft (P = 0.53), fixation (P = 0.72), or duraplasty (P = 0.80). Meningitis occurred in the Auto G S + G, Non-Auto G S + G and Non-Auto G S groups (25%, 48%, and 23.1%, respectively; P = 0.30), and their formations were not related to the k graft type (P = 0.57) or fixation (P = 0.19). CONCLUSIONS: Autologous and nonautologous dural grafts can be performed using either sutures or sutures plus glue, as both result in similar outcomes.

Based on clinical Ki-67 expression and serum infiltrating lymphocytes related nomogram for predicting the diagnosis of glioma-grading.

Background: Compelling evidence indicates that elevated peripheral serum lymphocytes are associated with a favorable prognosis in various cancers. However, the association between serum lymphocytes and glioma is contradictory. In this study, a nomogram was established to predict the diagnosis of glioma-grading through Ki-67 expression and serum lymphocytes. Methods: We performed a retrospective analysis of 239 patients diagnosed with LGG and 178 patients with HGG. Immunohistochemistry was used to determine the Ki-67 expression. Following multivariate logistic regression analysis, a nomogram was established and used to identify the most related factors associated with HGG. The consistency index (C-index), decision curve analysis (DCA), and a calibration curve were used to validate the model. Results: The number of LGG patients with more IDH1/2 mutations and 1p19q co-deletion was greater than that of HGG patients. The multivariate logistic analysis identified Ki-67 expression, serum lymphocyte count, and serum albumin (ALU) as independent risk factors associated with HGG, and these factors were included in a nomogram in the training cohort. In the validation cohort, the nomogram demonstrated good calibration and high consistency (C-index = 0.794). The Spearman correlation analysis revealed a significant association between HGG and serum lymphocyte count (r = -0.238, P <0.001), ALU (r = -0.232, P <0.001), and Ki-67 expression (r = 0.457, P <0.001). Furthermore, the Ki-67 expression was negatively correlated with the serum lymphocyte count (r = -0.244, P <0.05). LGG patients had lower Ki-67 expression and higher serum lymphocytes compared with HGG patients, and a combination of these two variables was significantly higher in HGG patients. Conclusion: The constructed nomogram is capable of predicting the diagnosis of glioma-grade. A decrease in the level of serum lymphocyte count and increased Ki-67 expression in HGG patients indicate that their immunological function is diminished and the tumor is more aggressive.

Long non-coding RNA LINC00488 facilitates thyroid cancer cell progression through miR-376a-3p/PON2.

OBJECTIVE: Long non-coding RNAs (lncRNAs) recently have been identified as influential indicators in a variety of malignancies. The aim of the present study was to identify a functional lncRNA LINC00488 and its effects on thyroid cancer in the view of cell proliferation and apoptosis. METHODS: In order to evaluate the effects of LINC00488 on the cellular process of thyroid cancer, we performed a series of in vitro experiments, including cell counting kit-8 (CCK-8) assay, EdU (5-ethynyl-2'-deoxyuridine) assay, flow cytometry, transwell chamber assay, Western blot and RT-qPCR. The target gene of LINC00488 was then identified by bioinformatics analysis (DIANA and TargetScan). Finally, a series of rescue experiments was conducted to validate the effect of LINC00488 and its target genes on proliferation, migration, invasion and apoptosis of thyroid cancer. RESULTS: Our findings revealed that LINC00488 was highly expressed in thyroid cancer cell lines (BCPAP, BHP5-16, TPC-1 and CGTH-W3) and promoted the proliferation, migration and invasion, while inhibited the apoptosis of thyroid cancer cells (BCPAP and TPC-1). The results of bioinformatics analysis and dual luciferase reporter gene assay showed that LINC00488 could directly bind to miR-376a-3p and down-regulated the expression level of miR-376a-3p. In addition, Paraoxonase-2 (PON2) was a target gene of miR-376a-3p and negatively regulated by miR-376a-3p. Rescue experiment indicated that LINC00488 might enhance PON2 expression by sponging miR-376a-3p in thyroid cancer. CONCLUSION: Taken together, our study revealed that lncRNA LINC00488 acted as an oncogenic gene in the progression of thyroid cancer via regulating miR-376a-3p/PON2 axis, which indicated that LINC00488-miR-376a-3p-PON2 axis could serve as novel biomarkers or potential targets for the treatment of thyroid cancer.

Nomogram Predicting Cancer-Specific Death in Parotid Carcinoma: a Competing Risk Analysis.

PURPOSE: Multiple factors have been shown to be tied to the prognosis of individuals with parotid cancer (PC); however, there are limited numbers of reliable as well as straightforward tools available for clinical estimation of individualized mortality. Here, a competing risk nomogram was established to assess the risk of cancer-specific deaths (CSD) in individuals with PC. METHODS: Data of PC patients analyzed in this work were retrieved from the Surveillance, Epidemiology, and End Results (SEER) data repository and the First Affiliated Hospital of Nanchang University (China). Univariate Lasso regression coupled with multivariate Cox assessments were adopted to explore the predictive factors influencing CSD. The cumulative incidence function (CIF) coupled with the Fine-Gray proportional hazards model was employed to determine the risk indicators tied to CSD as per the univariate, as well as multivariate analyses conducted in the R software. Finally, we created and validated a nomogram to forecast the 3- and 5-year CSD likelihood. RESULTS: Overall, 1,467 PC patients were identified from the SEER data repository, with the 3- and 5-year CSD CIF after diagnosis being 21.4% and 24.1%, respectively. The univariate along with the Lasso regression data revealed that nine independent risk factors were tied to CSD in the test dataset (n = 1,035) retrieved from the SEER data repository. Additionally, multivariate data of Fine-Gray proportional subdistribution hazards model illustrated that N stage, Age, T stage, Histologic, M stage, grade, surgery, and radiation were independent risk factors influencing CSD in an individual with PC in the test dataset (p < 0.05). Based on optimization performed using the Bayesian information criterion (BIC), six variables were incorporated in the prognostic nomogram. In the internal SEER data repository verification dataset (n = 432) and the external medical center verification dataset (n = 473), our nomogram was well calibrated and exhibited considerable estimation efficiency. CONCLUSION: The competing risk nomogram presented here can be used for assessing cancer-specific mortality in PC patients.

The Ki-67 Proliferation Index-Related Nomogram to Predict the Response of First-Line Tyrosine Kinase Inhibitors or Chemotherapy in Non-small Cell Lung Cancer Patients With Epidermal Growth Factor Receptor-Mutant Status.

Background: The correlation between Ki-67 and epidermal growth factor receptor (EGFR)- or Kristen rat sarcoma viral oncogene homolog (KRAS)-mutant status in advanced or postoperative-recurrent non-small cell lung cancer (NSCLC) has fewer studies reported, and the prognostic role of Ki-67 with first-line EGFR-tyrosine kinase inhibitors (TKIs) or chemotherapy remains controversial. Methods: A total of 295 patients were tested for EGFR-mutant status in advanced or postoperative-recurrent NSCLC and received first-line EGFR-TKIs or chemotherapy for treatment. Ki-67 expression was retrospectively analyzed by immunohistochemistry. The Kaplan-Meier method was used to calculate survival rates. The multivariate Cox proportional hazards model was used to generate a nomogram. The established nomogram was validated using the calibration plots. Results: The expression levels of Ki-67 were divided into low (<60%, n = 186) and high (≥60%, n = 109) groups, based on the receiver operating characteristic curve. The expression levels of Ki-67 were found to be higher in patients with KRAS mutations when compared to KRAS wildtype, and EGFR wildtype was higher than EGFR mutations. The median overall survival (OS) of the low Ki-67 expression group was significantly longer than that of the high Ki-67 group, no matter in all NSCLC, EGFR mutations, EGFR wildtype, KRAS-mutant status, EGFR-TKIs, or chemotherapy of patients (P < 0.05). Subgroup analysis showed that the KRAS wildtype or EGFR mutations combine with low Ki-67 expression group had the longest median OS than KRAS mutations or EGFR wildtype combine with Ki-67 high expression group (P < 0.05). In the training cohort, the multivariate Cox analysis identified age, serum lactate dehydrogenase (LDH), serum Cyfra211, EGFR mutations, and Ki-67 as independent prognostic factors, and a nomogram was developed based on these covariates. The calibration curve for predicting the 12-, 24-, and 30-month OS showed an optimal agreement between the predicted and actual observed outcomes. Conclusions: The Ki-67 expression-based nomogram can well predict the efficacy of first-line therapy in NSCLC patients with EGFR- or KRAS-mutant status, high expression levels of Ki-67 correlated with a poor prognosis.

miR-506-3p can inhibit cell proliferation and is a diagnostic and prognostic marker of liver cancer.

BACKGROUND: At the time of diagnosis, most patients with liver cancer (LC) are at advanced stage, which increases the difficulty of treatment. MiR-506-3p is considered an anti-oncogene in a wide spectrum of malignancies. This investigation aims to determine the clinical implications of miR-506-3p in diagnosis and prognosis of LC. METHODS: The expression of miR-506-3p in tissues and serum samples of 92 LC patients was detected using quantitative real-time PCR (qRT-PCR), and the connection between serum miR-506-3p and pathologic features of LC patients was analyzed. The diagnostic efficacy of miR-506-3p in LC was visualized by Receiver Operating Characteristic (ROC) curves, its prognostic implications in LC were confirmed by follow-up, and its impact on LC cell proliferation was analyzed by CCK-8 assay. RESULTS: miR-506-3p was lowly expressed in LC tissues and serum samples. Reduced serum miR-506-3p expression indicated larger tumor size, higher TNM stage, and poorer differentiation degree in LC patients. The area under the curve (AUC) of serum miR-506-3p in diagnosing LC was 0.911, and for distinguishing tumor size, TNM stage and pathologic differentiation degree, AUC was 0.751, 0.825 and 0.777, respectively. Kaplan-Meier analysis demonstrated decreased overall survival in patients presenting with reduced serum miR-506-3p. Cox proportional hazards regression model analysis revealed that TNM staging and low serum miR-506-3p expression were independent prognostic factors in patients with LC. In vitro experiments identified that the proliferation of LC cells decreased significantly following miR-506-3p up-regulation. CONCLUSION: miR-506-3p, capable of inhibiting LC cell proliferation, is a possible diagnostic and prognostic biomarker of LC.

A Competing Risk Nomogram for Predicting Cancer-Specific Death of Patients With Maxillary Sinus Carcinoma.

OBJECTIVES: Herein, we purposed to establish and verify a competing risk nomogram for estimating the risk of cancer-specific death (CSD) in Maxillary Sinus Carcinoma (MSC) patients. METHODS: The data of individuals with MSC used in this study was abstracted from the (SEER) Surveillance, Epidemiology, and End Results data resource as well as from the First Affiliated Hospital of Nanchang University (China). The risk predictors linked to CSD were identified using the CIF (cumulative incidence function) along with the Fine-Gray proportional hazards model on the basis of univariate analysis coupled with multivariate analysis implemented in the R-software. After that, a nomogram was created and verified to estimate the three- and five-year CSD probability. RESULTS: Overall, 478 individuals with MSC were enrolled from the SEER data resource, with a 3- and 5-year cumulative incidence of CSD after diagnosis of 42.1% and 44.3%, respectively. The Fine-Gray analysis illustrated that age, histological type, N stage, grade, surgery, and T stage were independent predictors linked to CSD in the SEER-training data set (n = 343). These variables were incorporated in the prediction nomogram. The nomogram was well calibrated and it demonstrated a remarkable estimation accuracy in the internal validation data set (n = 135) abstracted from the SEER data resource and the external validation data set (n = 200). The nomograms were well-calibrated and had a good discriminative ability with concordance indexes (c-indexes) of 0.810, 0.761, and 0.755 for the 3- and 5-year prognosis prediction of MSC-specific mortality in the training cohort, internal validation, and external validation cohort, respectively. CONCLUSIONS: The competing risk nomogram constructed herein proved to be an optimal assistant tool for estimating CSD in individuals with MSC.

Overexpression of Human Aspartyl (Asparaginyl) ß-hydroxylase in NSCLC: Its Diagnostic Value by Means of Exosomes of Bronchoalveolar Lavage.

The human aspartyl ß-hydroxylase (ASPH) is overexpressed in tumor tissues. Bronchoalveolar lavage (BAL) is a diagnostic procedure for infections and malignancies. The aim of this study was to investigate whether tumor exosomes carrying ASPH gene marker were present in bronchoalveolar fluid of patients with non-small cell lung cancer (NSCLC). A tissue microarray analysis was applied to explore the expression of ASPH in different histologic NSCLC. The human NSCLC cell lines and normal bronchial cell lines were used to study exosomal ASPH exprerssion. A total of 27 NSCLC, 21 benign tumor, and 15 healthy controls underwent BAL. Immunohistochemistry was performed to study the ASPH expression in malignant and normal lung tissues. The expression characteristics of ASPH in different NSCLC and normal bronchial cells and pneumocytes were confirmed by cell blocks. A reverse transcription-quantitative polymerase chain reaction was carried out to study the levels of exosomal ASPH expression. Immunohistochemical staining of tissue microarray demonstrated that overexpression of ASPH was found in NSCLC tissues including adenocarcinoma, large cell carcinoma, and squamous cell carcinoma, but absent in adjacent normal tissues. All NSCLC specimens exhibited high levels of ASPH immunoreactivity, while nonmalignant and normal lung tissues exhibited a very low level of expression. Overexpression of ASPH was found in exosomes from NSCLC cell lines but absent from the normal bronchial cell line NL-20. ASPH level from BAL exosomes was significantly increased in NSCLC patients compared with that from nonmalignant or health group. Our method of isolation of BAL exosomes was easily performed in the clinical laboratory. BAL exosomal ASPH can be a potential biomarker for NSCLC diagnosis.

Sex-related differences in the efficacy of immune checkpoint inhibitors in malignancy: a systematic review and meta-analysis.

Although disease susceptibility is known to differ between men and women, it is controversial whether the efficacy of immune checkpoint inhibitors for malignancies also differs between the sexes. We conducted a meta-analysis to explore the impact of sex on immune checkpoint inhibitor treatment outcomes. We searched PubMed, Embase and the Cochrane Library databases from inception to October 1, 2020 for randomized controlled trials of immune checkpoint inhibitors with hazard ratios (HRs) stratified by sex. We calculated the pooled HRs for men and women using the ln(HR), and assessed the heterogeneity between the two estimates through an interaction test. In total, 22,268 patients from 39 randomized controlled trials were included. Immune checkpoint inhibitors yielded better overall survival than conventional agents in both men (HR: 0.75, 95% confidence interval [CI]: 0.71-0.80) and women (HR: 0.77, 95% CI: 0.70-0.85). Progression-free survival benefits were also observed in both men (HR: 0.64, 95% CI: 0.58-0.70) and women (HR: 0.67, 95% CI: 0.58-0.77) treated with immune checkpoint inhibitors. No sex differences in the response to immune checkpoint inhibitors were found when overall survival and progression-free survival were used as the endpoints.

[Expression of HER2/neu in meningiomas: an immunohistochemistry and fluorescence in situ hybridization study].

OBJECTIVE: To investigate the expression of HER2/neu, Ki-67 and TK1 protein in meningiomas in correlation with tumor grades and recurrence. METHODS: Twenty cases of each of the following types of meningiomas were selected for the study, namely: the benign non-recurrent, recurrent benign, atypical and malignant, according to the World Health Organization (WHO) histological classification of nervous system, 2007. Immunohistochemistry study for HER2/neu, Ki-67 and TK1 protein was performed. HER2/neu gene amplification was detected using FISH. Cases with HER2 protein overexpression were studied by immunohistochemistry staining. The results of the biomarker assays were also used to study the correlationship with the tumor grades and tumor recurrency. RESULTS: Immunohistochemistry showed that the positive rates of HER2 expression in non-recurrence benign group, recurrence benign group, atypical group and malignant group were 3 cases (15%), 6 cases (30%), 7 cases (35%), and 10 cases (50%), respectively (P < 0.05). A higher tumor grade was correlated with a higher rate of HER2/neu expression. The Ki-67 and TK1 labeling index (LI) in non-recurrence group were lower than those in the atypical or malignant group (P < 0.05), whereas the atypical group had lower LI than that of the malignant group (P < 0.05). Higher levels of LI of Ki-67 and TK1 were correlated with higher tumor grades and recurrence of the benign meningiomas (P < 0.05). Expression of HER2 was positively correlated with Ki-67 and TK1 (r = 0.445, P < 0.01; r = 0.501, P < 0.01, respectively), and there was a positive correlation between Ki-67 and TK1 (r = 0.450, P < 0.01) as well. HER2/neu gene copy amplification in 7 of 26 cases (26.9%) of HER2 immunopositive meningiomas. The rates of HER2/neu gene amplification were 0 in tumors with 1+ immunopositivity, 4/6 in tumor with 2+ immunopositivity and 3/4 in tumor with 3+ immunopositivity. HER2/neu gene amplification in 3+ and 2+ immunopositive cases had no statistical significance (P > 0.05). Aneuploidy of chromosome 17 existed in 9 of 26 of HER2 immunopositive meningiomas (34.6%). However, the rates of chromosome 17 aneuploidy had no significant difference among tumors with variable HER2/neu imumopositivity (P > 0.05). CONCLUSIONS: High levels of HER2 and Ki-67 or TK1 expression correlate with the increase of tumor grades and tumor recurrence. HER2/neu gene amplification is seen in a subset of meningiomas with the protein expression (26.9%). A combination of biomarker study including HER2/neu, Ki-67 and TK1 may be useful in predicting the biological behavior of meningiomas.