scholarly journals HPV E6/E7 mRNA In Situ Hybridization in Endocervical Adenocarcinoma: Implications for Prognosis and Diagnosis

2021 ◽  
Author(s):  
Rong-Zhen Luo ◽  
Shu-Lin Chen ◽  
Mei Li ◽  
Yue Li ◽  
Xia Yang ◽  
...  
Keyword(s):  
Regression Analysis ◽  
In Situ Hybridization ◽  
Univariate Analysis ◽  
Figo Stage ◽  
Clinicopathological Parameters ◽  
Cox Regression Analysis ◽  
Endocervical Adenocarcinoma ◽  
Hpv E6 ◽  
Mrna In Situ Hybridization

Abstract Background: Human papillomavirus (HPV) E6/E7 mRNA in situ hybridization (HPV E6/E7 RNAscope) appears to be a sensitive and specific technique in detecting transcriptionally active HPV. We aimed to examine the diagnostic utility of this technique in endocervical adenocarcinoma (ECA), to explore the prognostic factors for ECA patients and develop a clinically useful nomogram based on clinicopathological parameters to predict it.Methods: We retrospectively analyzed 200 patients with ECA who had undergone surgery at Sun Yat-sen University Cancer Center from 2010 and 2014. The diagnostic performance of HPV E6/E7 RNAscope were evaluated by receiver operating characteristic (ROC) curve. A prognostic nomogram model including HPV E6/E7 RNAscope was generated based on multivariate Cox regression analysis, then we compared the predictive accuracy of the prognostic model with FIGO staging and treatment using concordance index (C-index), time-dependent ROC (tdROC), and decision curve analysis (DCA).Results: The sensitivity and specificity of HPV E6/E7 RNAscope for distinguishing HPV-associated adenocarcinoma (HPVA) from non-HPV-associated adenocarcinoma (NHPVA) in the whole cohort were 75.8% and 80%, respectively. According the univariate analysis and multivariate logistic regression analysis, age, lymphovascular invasion (LVI), lymph node involvement (LNI), and HPV E6/E7 RNAscope were valuable predictive factors for OS. These parameters were incorporated into the nomogram model (nomogram A) compared with FIGO stage and treatment. The C-index of nomogram A for predicting OS was 0.825, which was significantly higher than FIGO stage (C-index = 0.653, p=0.002) and treatment (C-index = 0.578, p < 0.001).Conclusions: HPV E6/E7 RNAscope is highly specific for ECA, and the 4-variable nomogram showed more accurate prognostic outcomes in patients with ECA.

scholarly journals HPV E6/E7 mRNA in situ hybridization in endocervical adenocarcinoma: implications for prognosis and diagnosis

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Rong-Zhen Luo ◽  
Shu-Lin Chen ◽  
Mei Li ◽  
Yue Li ◽  
Xia Yang ◽  
...  
Keyword(s):  
Regression Analysis ◽  
In Situ Hybridization ◽  
Univariate Analysis ◽  
Figo Stage ◽  
Clinicopathological Parameters ◽  
Cox Regression Analysis ◽  
Endocervical Adenocarcinoma ◽  
Hpv E6 ◽  
Mrna In Situ Hybridization

Abstract Background Human papillomavirus (HPV) E6/E7 mRNA in situ hybridization (HPV E6/E7 RNAscope) appears to be a sensitive and specific technique in detecting transcriptionally active HPV. We aimed to examine the diagnostic utility of this technique in endocervical adenocarcinoma (ECA), to explore the prognostic factors for ECA patients and develop a clinically useful nomogram based on clinicopathological parameters to predict it. Methods We retrospectively analyzed 200 patients with ECA who had undergone surgery at Sun Yat-sen University Cancer Center from 2010 and 2014. The diagnostic performance of HPV E6/E7 RNAscope were evaluated by receiver operating characteristic (ROC) curve. A prognostic nomogram model including HPV E6/E7 RNAscope was generated based on multivariate Cox regression analysis, then we compared the predictive accuracy of the prognostic model with FIGO staging and treatment using concordance index (C-index), time-dependent ROC (tdROC), and decision curve analysis (DCA). Results The sensitivity and specificity of HPV E6/E7 RNAscope for distinguishing HPV-associated adenocarcinoma (HPVA) from non-HPV-associated adenocarcinoma (NHPVA) in the whole cohort were 75.8% and 80%, respectively. According the univariate analysis and multivariate logistic regression analysis, age, lymphovascular invasion (LVI), lymph node involvement (LNI), and HPV E6/E7 RNAscope were valuable predictive factors for OS. These parameters were incorporated into the nomogram model (nomogram A) compared with FIGO stage and treatment. The C-index of nomogram A for predicting OS was 0.825, which was significantly higher than FIGO stage (C-index = 0.653, p = 0.002) and treatment (C-index = 0.578, p < 0.001). Conclusions  HPV E6/E7 RNAscope is highly specific for ECA, and the 4-variable nomogram showed more accurate prognostic outcomes in patients with ECA.

scholarly journals Prognostic nomogram for patients with invasive endocervical adenocarcinoma incorporating HPV E6/E7 mRNA in situ hybridization and clinical characteristics

2020 ◽  
Author(s):  
Li-Li Liu ◽  
Shu-Lin Chen ◽  
Shu-Mei Yan ◽  
Yue Li ◽  
Xia Yang ◽  
...  
Keyword(s):  
In Situ Hybridization ◽  
Multivariable Analysis ◽  
Figo Stage ◽  
Cancer Center ◽  
Specific Method ◽  
Endocervical Adenocarcinoma ◽  
Hpv E6 ◽  
Mrna In Situ Hybridization ◽  
Significant Difference

Abstract Background: Human papillomavirus (HPV) E6/E7 mRNA in situ hybridization (HPV E6/E7 RNAscope) appears to be a sensitive and specific method. We aimed to examine the diagnostic and prognostic utility of this technique in endocervical adenocarcinoma (ECA) and build a useful prognostic nomogram model using this approach. Methods: The model was constructed from a retrospective study of 200 patients with ECA who had undergone surgery at Sun Yat-sen University Cancer Center between 2010 and 2014. The model's predictive efficiency and discriminative capability were defined by a concordance index (C-index) and calibration curve. Results: The overall sensitivity and specificity of HPV E6/E7 RNAscope for distinguishing HPV-associated adenocarcinoma (HPVA) from non HPV-associated adenocarcinoma (NHPVA) in the whole cohort were 75.8% and 80%, respectively, compared to 60.2% and 90.0% for p16 immunohistochemistry, 80.5% and 80.0% for HPV DNA, and 63.3% and 50% for HPV genotype. The independent factors derived from multivariable analysis of the whole cohort to predict overall survival (OS) were age, lymphovascular invasion (LVI), lymph node involvement (LNI), and HPV E6/E7 RNAscope, which were all incorporated into the nomogram with (nomogram B) or without (nomogram A) FIGO stage and treatment. The C-index of nomogram A for predicting OS was 0.825 (p = 0.002 and p < 0.001), which was significantly higher than the C-index for FIGO stage (0.653) and treatment (0.578). No significant difference occurred between nomograms A (0.825) and B (0.836). Furthermore, a risk stratification system was established to accurately stratify patients with ECA into two subgroups with significantly different prognosis. Conclusions: HPV E6/E7 RNAscope is highly specific for ECA, and the proposed nomogram using HPV E6/E7 RNAscope showed more accurate outcome in terms of prognosis in patients with ECA.

HR-HPV E6/E7 mRNA In Situ Hybridization

2017 ◽  
Vol 41 (5) ◽  
pp. 607-615 ◽  
Author(s):  
Anne M. Mills ◽  
Dawn C. Dirks ◽  
Melinda D. Poulter ◽  
Stacey E. Mills ◽  
Mark H. Stoler
Keyword(s):  
In Situ Hybridization ◽  
Hpv E6 ◽  
Mrna In Situ Hybridization

scholarly journals The Expression of HPV E6/E7 mRNA in Situ Hybridization in HPV Typing-negative Cervical Cancer

2021 ◽  
Author(s):  
Yating Xu ◽  
Yonghong Sun ◽  
Hui Chang ◽  
Jingjing Cai ◽  
Chengcheng Cao ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
In Situ Hybridization ◽  
Hpv Infection ◽  
Detection Methods ◽  
Positive Group ◽  
Hpv E6 ◽  
Mrna In Situ Hybridization ◽  
Hpv Typing ◽  
Significant Difference

Abstract Background: High-risk human papilloma virus (HR-HPV) persistent infection is the major tumorigenesis factor for cervical cancer (CC) and cervical intraepithelial neoplasia (CIN). However, the incidence of HPV-negative CC is approximately 5%-30% with different HPV detection methods. HR-HPV E6/E7 mRNA in situ hybridization (RISH) can detect HPV-driven tumours. Our study aimed to explore whether HPV typing-negative CC was caused by HPV infection.Methods: The records of CC patients with HPV typing results who had undergone cervical biopsies, cervical conization or hysterectomies were collected from April 2018 to September 2021 at the Affiliated Hospital of Weifang Medical University. RISH was detected using RNAscope chromogenicin in the tissues of patients with CC. Immunohistochemistry (IHC) was performed to evaluate the expression of p16INK4a and Ki67. CC patients with positive HPV typing in the same period were collected as controls.Results: A total of 308 women with HPV typing results were enrolled, and 30 (9.74%) cases of HPV typing were negative, including 22/30 (73.3%) cases of squamous cell carcinoma (SCC) and 8/30 (26.7%) cases of adenocarcinoma. In the CC patients who were HPV typing-negative, 28/30 (93.3%) were positive for RISH and p16INK4a block+ staining, which contained 22/22 (100%) SCCs and 6/8 (75%) adenocarcinomas. RISH was positive in 278/278 (100%) HPV typing-positive CCs, which included 232/232 (100%) SCCs and 46/46 (100%) adenocarcinomas. While 273/278 (98.2%) showed p16INK4a block+ staining, the five negative cases were SCC. Positive RISH in HPV typing-negative CC was significantly lower than in the HPV typing-positive group (P=0.002, 95% CI: 0.848-1.027). However, this significant difference only existed in adenocarcinoma, and positive RISH in HPV typing-negative SCC was the same as in the HPV typing-positive group. No significant differences were seen in the expression of p16INK4a and Ki67 (P=0.291, 95% CI: 0.863-1.047 and P=0.174, 95% CI: 0.905-1.033).Conclusions: HPV typing may cause misdiagnosis in 9.74% of CC patients, and HPV E6/E7 mRNA can detect the majority of CC with HPV-related status even in HPV typing-negative patients. This approach could provide a novel option to accurately detect HR-HPVs in cervical tumours and help to eliminate the percentage of misdiagnosed HPV-related cases.

scholarly journals Construction and Validation of a Prognostic Risk Model Based on Autophagy-Related Genes in Hepatocellular Carcinoma Cells

2021 ◽  
Author(s):  
Rui Feng ◽  
Jian Li ◽  
Weiling Xuan ◽  
Hanbo Liu ◽  
Dexin Cheng ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Regression Analysis ◽  
Differential Expression ◽  
Prognostic Model ◽  
Risk Model ◽  
Cox Regression ◽  
Univariate Analysis ◽  
Differential Expression Analysis ◽  
Cox Regression Analysis ◽  
Dismal Prognosis

Abstract Background Hepatocellular carcinoma (HCC) is a prevalent primary liver cancer and the main cause of cancer mortality. Its high complexity and dismal prognosis bring dramatic difficulty to treatment. Due to the disclosed dual functions of autophagy in cancer development, understanding autophagy-related genes devotes into seeking novel biomarkers for HCC. Methods Differential expression of genes in normal and tumor groups was analyzed to acquire autophagy-related genes in HCC. GO and KEGG pathway analyses were conducted on these genes. Genes were then screened by univariate regression analysis. The screened genes were subjected to multivariate Cox regression analysis to build a prognostic model. The model was validated by ICGC validation set. Results Altogether, 42 autophagy-related differential genes were screened by differential expression analysis. Enrichment analysis showed that they were mainly enriched in pathways including regulation of autophagy and cell apoptosis. Genes were screened by univariate analysis and multivariate Cox regression analysis to build a prognostic model. The model was constituted by 6 feature genes: EIF2S1, BIRC5, SQSTM1, ATG7, HDAC1, FKBP1A. Validation confirmed the accuracy and independence of this model in predicting HCC patient’s prognosis. Conclusion A total of 6 feature genes were identified to build a prognostic risk model. This model is conducive to investigating interplay between autophagy-related genes and HCC prognosis.

scholarly journals Transcriptome-Wide Analyses Provide Insights into Development of the Hedychium Coronarium Flower, Revealing Potential Roles of PTL

2020 ◽  
Author(s):  
Tong Zhao ◽  
Alma Piñeyro-Nelson ◽  
Qianxia Yu ◽  
Xiaoying Hu ◽  
Huanfang Liu ◽  
...  
Keyword(s):  
In Situ Hybridization ◽  
Flower Development ◽  
Molecular Mechanisms ◽  
Expression Patterns ◽  
Floral Organ ◽  
Mrna In Situ Hybridization ◽  
Hedychium Coronarium ◽  
Organ Identity

Abstract Background:The flower of Hedychium coronarium possesses highly specialized floral organs: a synsepalous calyx, petaloid staminodes and a labellum. The formation of these organs is controlled by two gene categories: floral organ identity genes and organ boundary genes, which may function individually or jointly during flower development. Although the floral organogenesis of H. coronarium has been studied at the morphological level, the underlying molecular mechanisms involved in its floral development still remain poorly understood. In addition, previous works analyzing the role of MADS-box genes in controlling floral organ specification in some Zingiberaceae did not address the molecular mechanisms involved in the formation of particular organ morphologies that emerge later in flower development, such as the synsepalous calyx formed through intercalary growth of adjacent sepals. Results:Here, we used comparative transcriptomics combined with Real-time quantitative PCR and mRNA in situ hybridization to investigate gene expression patterns of ABC-class genes in H. coronarium flowers, as well as the homolog of the organ boundary gene PETAL LOSS (HcPTL). qRT-PCR detection showed that HcAP3 and HcAG were expressed in both the petaloid staminode and the fertile stamen. mRNA in situ hybridization showed that HcPTL was expressed in developing meristems, including cincinnus primordia, floral primordia, common primordia and almost all new initiating floral organ primordia.Conclusions:Our studies found that stamen/petal identity or stamen fertility in H. coronarium was not necessarily correlated with the differential expression of HcAP3 and HcAG. We also found a novel spatio-temporal expression pattern for HcPTL mRNA, suggesting it may have evolved a lineage-specific role in the morphogenesis of the Hedychium flower. Our study provides a new transcriptome reference and a functional hypothesis regarding the role of a boundary gene in organ fusion that should be further addressed through phylogenetic analyzes of this gene, as well as functional studies.

scholarly journals Association of methicillin resistance with mortality of hospital-acquired Staphylococcus aureus bacteremia

2021 ◽  
Vol 49 (11) ◽  
pp. 030006052110588
Author(s):  
Tomonori Aratani ◽  
Hitoshi Tsukamoto ◽  
Takashi Higashi ◽  
Takaaki Kodawara ◽  
Ryoichi Yano ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Regression Analysis ◽  
Cox Regression ◽  
Methicillin Resistance ◽  
Univariate Analysis ◽  
Cox Regression Analysis ◽  
Staphylococcus Aureus Bacteremia ◽  
Mortality Outcome ◽  
Delayed Initiation ◽  
Hospital Acquired

Objective Methicillin-resistant (MR) Staphylococcus aureus bacteremia (SAB) is associated with higher mortality rates than methicillin-susceptible (MS) SAB. This study assessed potential predictors of mortality and evaluated the association of methicillin resistance with mortality in patients with SAB. Methods We conducted a retrospective cohort study in patients with hospital-acquired SAB, from 2009 to 2018. Clinical features of patients with MR-SAB were compared with those of patients with MS-SAB and predictors of 30-day mortality were determined using Cox regression analysis. Results Among 162 patients, 56.8% had MR-SAB. Overall 30-day mortality was 19.1%; MR-SAB had higher mortality (25.0%) than MS-SAB (11.4%). Univariate analysis highlighted long-term hospitalization, prior antibiotics use, and delayed initiation of appropriate antibiotics as risk factors. Cox regression analysis showed that respiratory tract source, Pitt bacteremia score, Charlson comorbidity index, and appropriate antibiotic therapy within 24 hours were independently and significantly associated with 30-day mortality outcome. Conclusions Methicillin resistance was not an independent risk factor for mortality in patients with SAB. Early, appropriate antibiotic treatment is an important prognostic factor.

Clinicopathological Features and Prognosis of Gastric Neuroendocrine Neoplasms

2020 ◽  
Author(s):  
Yajie Wang ◽  
Bei Wen ◽  
Shubo Tian ◽  
Kangdi Dong ◽  
Yuan Liu ◽  
...  
Keyword(s):  
Regression Analysis ◽  
Distant Metastasis ◽  
Univariate Analysis ◽  
Clinicopathological Features ◽  
Neuroendocrine Neoplasm ◽  
Open Approach ◽  
Primary Tumor Site ◽  
Cox Regression Analysis ◽  
Surgical Method ◽  
T Stage

Abstract Purpose: We performed a retrospective study to investigate the relationship between clinicopathological features and prognosis of G-NEN.Methods: Clinicopathological features and follow-up data of 67 patients with G-NEN treated at Shandong Provincial Hospital affiliated of Shandong University were analyzed retrospectively. Results: This whole cohort included 53 males and 14 females, with a mean age of 59.37±9.80 years. The clinical symptoms and the primary tumor site were not specific. Neuroendocrine tumor, neuroendocrine carcinoma, and mixed neuroendocrine–non‐neuroendocrine neoplasm accounted for 14.93%, 59.70%, and 25.37%, respectively. TNM stages Ⅰ-Ⅳ: 6, 6, 49, 4, respectively. All patients underwent surgically treated. Forty-five patients underwent laparoscopic surgery, and twenty-two patients received an open approach. The median survival time was 36 months in all patients. The overall survival rate for the entire cohort was 68.1 %, 44.7 %, and 34.5% at 1, 3, and 5 years, respectively. Logistic regression analysis revealed that the invasive depth of tumors was predictors for metastasis. The univariate analysis confirmed that smoking, T stage, distant metastasis, and surgical method were related to survival. COX regression analysis showed that the T stage (HR=4.817, 95%CI: 1.021-22.729, P=0.047) was an independent risk factor for evaluating the prognosis of patients with G-NEN.Conclusions: G-NEN is a kind of rare tumors that can occur at any part of the stomach. The clinical features are not specific. The tumor invasive depth related to tumor metastasis. The prognosis is associated with smoking, T stage, distant metastasis, and surgical method. Of them, T stage is an independent prognostic factor for G-NEN patients. But larger studies are needed in the future.

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