scholarly journals Polo like kinase 1 expression in cervical cancer tissues generated from multiple detection methods

PeerJ ◽  
2020 ◽  
Vol 8 ◽  
pp. e10458
Author(s):  
Li Gao ◽  
Yu-Yan Pang ◽  
Xian-Yu Guo ◽  
Jing-Jing Zeng ◽  
Zhong-Qing Tang ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Cancer Patients ◽  
Tissue Microarrays ◽  
Cervical Adenocarcinoma ◽  
Rna Seq ◽  
Event Free Survival ◽  
Survival Curves ◽  
Free Survival ◽  
Kaplan Meier ◽  
Plk1 Expression

Background Existing studies of PLK1 in cervical cancer had several flaws. The methods adopted by those studies of detecting PLK1 expression in cervical cancer were single and there lacks comprehensive evaluation of the clinico-pathological significance of PLK1 in cervical cancer. Methods A total of 303 cervical tissue samples were collected for in-house tissue microarrays. Immunohistochemistry was performed for evaluating PLK1 expression between cervical cancer (including cervical squamous cell carcinoma (CESC) and cervical adenocarcinoma) and non-cancer samples. The Expression Atlas database was searched for querying PLK1 expression in different cervical cancer cell lines and different tissues in the context of pan-cancer. Standard mean difference (SMD) was calculated and the summarized receiver’s operating characteristics (SROC) curves were plotted for integrated tissue microarrays, exterior high-throughput microarrays and RNA sequencing data as further verification. The effect of PLK1 expression on the overall survival, disease-free survival and event-free survival of cervical cancer patients was analyzed through Kaplan Meier survival curves for cervical cancer patients from RNA-seq and GSE44001 datasets. The gene mutation and alteration status of PLK1 in cervical cancer was inspected in COSMIC and cBioPortal databases. Functional enrichment analysis was performed for genes correlated with PLK1 from aggregated RNA-seq and microarrays. Results A total of 963 cervical cancer samples and 178 non-cancer samples were collected from in-house tissue microarrays and exterior microarrays and RNA-seq datasets. The combined expression analysis supported overexpression of PLK1 in CESC, cervical adenocarcinoma and all types of cervical cancer (SMD = 1.59, 95%CI [0.56–2.63]; SMD = 2.99, 95%CI [0.75–5.24]; SMD = 1.57, 95% CI [0.85–2.29]) and the significant power of PLK1 expression in distinguishing CESC or all types of cervical cancer samples from non-cancer samples (AUC = 0.94, AUC = 0.92). Kaplan-Meier survival curves showed that the event-free survival rate of cervical cancer patients with higher expression of PLK1 was shorter than that of patients with lower PLK1 (HR = 2.020, P = 0.0197). Genetic alteration of PLK1 including missense mutation and mRNA low occurred in 6% of cervical cancer samples profiled in mRNA expression. Genes positively or negatively correlated with PLK1 were mainly assembled in pathways such as DNA replication, cell cycle, mismatch repair, Ras signaling pathway, melanoma, EGFR tyrosine kinase inhibitor resistance and homologous recombination (P < 0.05). Conclusions Here, we provided sufficient evidence of PLK1 overexpression in cervical cancer. The overexpression of PLK1 in cervical cancer and the contributory effect of it on clinical progression indicated the hopeful prospect of PLK1 as a biomarker for cervical cancer.

scholarly journals OP0294 SJÖGREN’S SYNDROME ASSOCIATED LYMPHOMAS: CLINICAL DESCRIPTION AND 10-YEAR SURVIVAL

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 180-181
Author(s):  
L. Chatzis ◽  
V. Pezoulas ◽  
A. Goules ◽  
I. Stergiou ◽  
C. Mavragani ◽  
...  
Keyword(s):  
Overall Survival ◽  
T Cell ◽  
Cell Lymphoma ◽  
T Cell Lymphoma ◽  
Histologic Type ◽  
Single Center ◽  
Event Free Survival ◽  
Survival Curves ◽  
Free Survival ◽  
Kaplan Meier

Background:Sjögren’s Syndrome (SS) is a chronic systemic autoimmune disease of unknown etiology, carrying the highest lymphoma risk among autoimmune diseases, with significant impact on mortality and morbidity of patients.Objectives:To describe: i) the clinical phenotype of SS, ii) the histologic type, stage, treatment options regarding lymphomas and iii) the prognosis of patients with SS related lymphoproliferative disorders.Methods:Eight hundred and fifteen consecutive SS patients’ records from a single center fulfilling the 2016 ACR/EULAR were reviewed retrospectively for the purpose of this study. One hundred twenty-one patients with a diagnosis of non-Hodgkin Lymphoma (NHL) were identified and enrolled in the study population. Cumulative clinical, laboratory and histologic data were recorded and overall survival as well as event free survival curves were constructed using the Kaplan-Meier method. An event was defined as a disease progression, lymphoma relapse, treatment failure, histologic transformation, development of a 2nd lymphoma or death from any cause.Results:From 121 pSS patients with lymphoma the most common histologic type encountered was MALT lymphoma (92/121, 76,0%) followed by DLBCL (11/121, 9.0%) and NMZL (8/119, 6.6%). The remaining 10 patients had various lymphomas of B (follicular, lymphoplasmacytic, chronic lymphocytic leukemia} and T cell origin (peripheral T cell lymphoma not otherwise specified, primary cutaneous T cell lymphoma, angioimmunoblastic t-cell lymphoma). Permanent salivary gland enlargement (66.1%, 80/121), palpable purpura (34,7% 42/121), peripheral nervous involvement (9,9%, 12/121), interstitial lung disease (8,2%, 10/121) presence of serum cryoglobulins (38,7%, 43/111) and C4 hypocomplementemia (69,8% 81/116) present at least 1 year before the development of lymphoma were the main pSS related features. The median age at lymphoma diagnosis was 58 years old (range 29-82) while MALT lymphomas developed earlier compared to DLBCL from pSS diagnosis (8 vs 3 OR= 3.84, 95%CI: 0.29 to 10.46; p=0.0266). The commonest biopsy proven extranodal sites included the labial minor salivary (43,8% patients) and parotid glands (30,5%) while 11% of patients had more than 1 extranodal sites affected. Bone marrow involvement was evident in 24,3% of patients (29/119) while nodal involvement in 35,5% (42/118). The majority of patients (65%) had limited disease (stage I or II). A watch and wait therapeutic policy was chosen in 40 patients while the rest received rituximab with or without chemotherapy. The 10-year survival and event free rates were 79% and 45,5% for MALT lymphomas, 40,9% and 24,2% for DLBCL and 46% and 31% for NMZL respectively (Figure 1). The Mantel-Cox log-rank comparison of the overall survival curves revealed a statistically significant difference (p=0.0016) among lymphoma subtypes.Figure 1.Overall and event free survival of SS-associated lymphoma patients. A. Kaplan-Meier overall survival analysis. B. A Kaplan-Meier event free survival analysis.Conclusion:This is the largest single center series of SS- associated lymphoma patients, providing a detailed description of SS and lymphoma related features, combined with a 10-year survival and event free curves for the first time in the literature.Disclosure of Interests:None declared.

Effect of mast cells on efficacy of anti-angiogenic therapy by secreting matrix-degrading granzyme b.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 11522-11522
Author(s):  
Mark Wroblewski ◽  
Janna-Lisa Velthaus ◽  
Raimund Bauer ◽  
Volkmar Müller ◽  
Christian Schem ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Granzyme B ◽  
Resistance Mechanism ◽  
Disease Free Survival ◽  
Tissue Microarrays ◽  
Breast Cancer Patients ◽  
Free Survival ◽  
Angiogenic Therapy ◽  
Kaplan Meier

11522 Background: Resistance towards anti-angiogenic therapy (AAT) still represents a substantial clinical challenge. As mast cell (MC) density is known to correlate with tumor angiogenesis, we analyzed if inhibition of MC holds potential to increase efficacy of AAT in mice and cancer patients. Methods: C57BL/6J (WT), NSG or MC-deficient KitW-sh(Wsh) mice were subcutaneously injected with Panc02, EL4 or BxPC3 cells with or without bone marrow-derived MC. Tumors were treated with 20 mg/kg of anti-VEGFR2 antibodies (DC101) or 25 mg/kg cromoglicic acid. Tissue microarrays from n = 299 breast cancer patients from the GeparQuinto Phase 3 clinical trial were stained for MC and MC numbers were correlated with clinical data. Results: We observed that absence of MC reduced tumor growth and increased the efficacy of AAT in different tumor models. Intriguingly, AAT only initially reduced microvessel proliferation but this was abrogated over time as a result of MC-mediated resistance. We show that MC secrete increased amounts of granzyme b upon therapy, which mobilizes alternative pro-angiogenic factors from the tumor matrix. These factors act beside the targeted VEGFA-VEGFR2-axis and reinduce angiogenesis despite the presence of AAT. Importantly, MC-mediated resistance could be overcome using the FDA-approved MC inhibitor cromoglicic acid. In line with our preclinical data, high intratumoral MC density correlated with disease progression in HR+ breast cancer patients when Bevacizumab was added to standard neodjuvant chemotherapy (HR 8.45, p = 0.006). Accordingly, Kaplan-Meier curves indicated that disease free survival of patients with high tumoral MC density was numerically shorter in the whole cohort and significantly shorter in the HR+ cohort upon addition of AAT to chemotherapy (p = 0.168 and p = 0.004, respectively). Conclusions: Here we unravel a novel resistance mechanism, by which MC hamper efficacy of AAT in mice and cancer patients. In preclinical models this effect could be overcome by combining AAT with an FDA-approved MC inhibitor indicating high clinical relevance. Thus, combination of FDA-approved MC inhibitors with AAT might be a suitable approach to increase efficacy of AAT in the clinic.

scholarly journals Potential prognostic factors in progression-free survival for patients with cervical cancer

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Hui-Hui Chen ◽  
Wei-Yu Meng ◽  
Run-Ze Li ◽  
Qing-Yi Wang ◽  
Yu-Wei Wang ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Prognostic Factors ◽  
Lymph Nodes ◽  
Cancer Patients ◽  
Survival Curve ◽  
Progression Free Survival ◽  
Curve Analysis ◽  
Free Survival ◽  
Kaplan Meier ◽  
Initial Symptoms

Abstract Background Cervical cancer continues to be one of the leading causes of cancer deaths among females in low and middle-income countries. In this study, we aimed to assess the independent prognostic value of clinical and potential prognostic factors in progression-free survival (PFS) in cervical cancer. Methods We conducted a retrospective study on 92 cervical cancer patients treated from 2017 to 2019 at the Zhuhai Hospital of Traditional Chinese and Western Medicine. Tumor characteristics, treatment options, progression-free survival and follow-up information were collected. Kaplan–Meier method was used to assess the PFS. Results Results showed that the number of retrieved lymph nodes had a statistically significant effect on PFS of cervical cancer patients (P = 0.002). Kaplan-Meier survival curve analysis showed that cervical cancer patients with initial symptoms age 25–39 had worse survival prognoses (P = 0.020). And the using of uterine manipulator in laparoscopic treatment showed a better prognosis (P < 0.001). A novel discovery of our study was to verify the prognostic values of retrieved lymph nodes count combining with FIGO staging system, which had never been investigated in cervical cancer before. According to the Kaplan-Meier survival curve analysis and receiver operating characteristic (ROC) curve analysis, significant improvements were found after the combination of retrieved lymph nodes count and FIGO stage in predicting PFS for cervical cancer patients (P < 0.001, AUC = 0.826, 95% CI: 0.689–0.962). Conclusion Number of retrieved lymph nodes, initial symptoms age, uterine manipulator, and retrieved lymph nodes count combining with FIGO staging system could be potential prognostic factors for cervical cancer patients.

Gasdermin D as a potential prognosis and treatment response prediction biomarker for invasive breast cancer.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e12548-e12548
Author(s):  
Xianghou Xia ◽  
Wenjuan Yin ◽  
Jiefei Mao ◽  
Jiejie Hu ◽  
Dehong Zou ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Invasive Breast Cancer ◽  
Response Prediction ◽  
Chemotherapy Response ◽  
Breast Cancer Patients ◽  
Free Survival ◽  
Kaplan Meier ◽  
Kaplan Meier Plotter ◽  
Treatment Response Prediction

e12548 Background: Pyroptosis is a type of inflammatory cell death mediated by gasdermins. Pyroptosis is critical for macrophage against pathogen infection. Recently growing evidences show that pyroptosis may affect development and progression of many cancers. We aim to explore the expression and related function of pyroptosis executioner Gasdermin D (GSDMD) in breast cancer. Methods: We investigated the expression level of GSDMD using TNM plotter and Breast Cancer landscape proteome with TCGA, GTEx and TARGET databases, and the prognostic value of GSDMD in invasive breast cancer using Kaplan-Meier plotter with TCGA, GEO and EGA databases. The treatment response prediction values of GSDMD in invasive breast were calculated using ROC-plotter with GEO database. Further validation of the prognostic value and chemotherapy response prediction value of GSDMD were carried out with immunohistochemical staining on tissues from 165 cases of breast cancer patients receiving neoadjuvant chemotherapy in our cancer center. Results: TNM plotter and breast cancer landscape proteome portal analysis shows that overall expression level of GSDMD in invasive breast cancer tissue is 1.67 folds higher than it is in breast normal tissues ( p=1.05*e-06). Expression of GSDMD in LuminalB subtype (p=0.019) and Her2 subtype(p=0.04) is significantly higher than it is in TNBC subtype. Calculations with Kaplan-Meier plotter show expression of GSDMD is negatively correlated with overall survival(OS), HR=0.61(0.4−0.95) p=0.027 and relapse free survival (RFS), HR =0.65(0.58−0.63), p=8.7*e-14 and distant metastasis free survival (DMFS) HR =0.75(0.61−0.91), p=0.0038 in breast cancer patients. ROC-plotter calculations show high GSDMD expression is a powerful endocrine therapy (AUC=0.731 p=6*e-09 ) and chemotherapy response (AUC=0.64 p=8*e-05 ) predictor based on 5-year RFS in overall breast cancer patients. Our IHC staining analysis shows consistent prognostic and chemotherapy prediction value of GSDMD expression in TNBC patients. Conclusions: In conclusion, our findings suggest that high expression of GSDMD is positively correlated with prognosis and therapeutic response in breast cancer. GSDMD is a promising prognostic marker and therapeutic response predictor in invasive breast cancer.

scholarly journals Prognostic implication of human papillomavirus types in cervical cancer patients: a systematic review and meta-analysis

2020 ◽  
Vol 15 (1) ◽  
Author(s):  
Yuanyuan Xu ◽  
Yichao Qiu ◽  
Shuang Yuan ◽  
Hongjing Wang
Keyword(s):  
Cervical Cancer ◽  
Human Papillomavirus ◽  
Cancer Patients ◽  
Meta Analysis ◽  
Disease Free Survival ◽  
Progression Free Survival ◽  
Hpv 16 ◽  
Free Survival ◽  
American Society ◽  
Hpv 18

Abstract Background To estimate the prognostic relevance of human papillomavirus (HPV) 16 and HPV 18 in patients with cervical cancer. Method We searched PubMed, EMBASE, American Society of Clinical Oncology (ASCO) and the European Society of Medical Oncology (ESMO), CNKI, and Wanfang databases to search primary articles illustrating the survival outcomes in cervical cancer patients with or without HPV 16/18 infection. A meta-analysis was conducted to generate a combined hazard ratio (HR) with 95% confidence intervals (CI) for progression-free survival (PFS), disease free survival (DFS) and overall survival (OS). Results A total of 13 studies were included. Our meta-analysis revealed that HPV 16 positive did not have any impact on OS (HR, 0.76; 95% CI = 0.37–1.54; P = 0.44). Cervical cancer patiensts infected with HPV 18 had worse OS (HR, 1.66; 95% CI = 1.28–2.17; P = 0.0001), DFS (HR, 2.10; 95% CI = 1.73–2.54; P < 0.0001) and worse PFS (HR, 2.97; 95% CI = 1.69–5.23; P = 0.00012) compared with those not infected with HPV 18. cervical cancer patiensts infected with HPV 18 had worse PFS compared with those infected with HPV 16 ((HR, 1.34; 95% CI = 1.06–1.70; P = 0.01). Conclusion Cervical cancer patients infected with HPV 18 had worse survival compared with cervical cancer patients with HPV 16 infection.

Outcomes of abandoned radical hysterectomy in patients with stages IB–IIA cervical cancer found to have positive nodes during the operation

2005 ◽  
Vol 15 (3) ◽  
pp. 498-502 ◽  
Author(s):  
P. Suprasert ◽  
J. Srisomboon ◽  
K. Charoenkwan ◽  
S. Siriaungul ◽  
S. Khunamornpong ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Cancer Patients ◽  
Radical Hysterectomy ◽  
Disease Free Survival ◽  
Pelvic Lymphadenectomy ◽  
Adjuvant Radiation ◽  
Free Survival ◽  
Number Of Patients ◽  
Extended Field ◽  
Disease Free

The objective of this study was to evaluate the outcomes of stages IB–IIA cervical cancer patients whose radical hysterectomy (RH) was abandoned for positive pelvic nodes detected during the operation compared with those found to have positive nodes after the operation. Among 242 patients with planned RH and pelvic lymphadenectomy (RHPL) for stages IB–IIA cervical cancer, 23 (9.5%) had grossly positive nodes. RH was abandoned, and complete pelvic lymphadenectomy was performed. Of these 23 patients, 22 received adjuvant chemoradiation, and the remaining 1 received adjuvant radiation. Four patients with positive para-aortic nodes were additionally treated with extended-field irradiation. When compared with 35 patients whose positive nodes were detected after the operation, there were significant differences regarding number of positive nodes and number of patients receiving extended-field irradiation. Complications in both groups were not significantly different, but the 2-year disease-free survival was significantly lower in the abandoned RH group compared with that of the RHPL group (58.5% versus 93.5%, P = 0.01). In conclusion, the survival of stages IB–IIA cervical cancer patients whose RH was abandoned for grossly positive pelvic nodes was significantly worse than that of patients whose node metastasis was identified after the operation. This is because the abandoned RH group had worse prognostic factors.

scholarly journals TILs and Anti-PD1 Therapy: An Alternative Combination Therapy for PDL1 Negative Metastatic Cervical Cancer

2020 ◽  
Vol 2020 ◽  
pp. 1-11 ◽  
Author(s):  
Huanhuan Yin ◽  
Wei Guo ◽  
Xiangling Sun ◽  
Ruili Li ◽  
Cuihua Feng ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Overall Survival ◽  
Combination Therapy ◽  
Survival Time ◽  
Response Rate ◽  
Multivariate Analyses ◽  
Objective Response ◽  
Progression Free Survival ◽  
Free Survival ◽  
Kaplan Meier

Background. We investigated the efficacy of TILs and anti-PD1 combination therapy in patients with metastatic cervical cancer with low MSI expression and PDL1-negative. Methods. A total of 80 patients were put on TILs and anti-PD1 combination therapy, and the progression-free survival time (PFS) and overall survival time (OS) were assessed by Kaplan–Meier analysis. Univariate and multivariate analyses were performed to identify factors that could predict the prognosis of metastatic cervical cancer in the previously described patients. Results. The objective response rate was 25%, whereas the mPFS and mOS were 6.1 and 11.3 months, respectively. The therapeutic efficacy was influenced by the characteristics of TILs, infection with HPV, and development of fever just after the therapy. Conclusion. Overall, our results show that the combination therapy of TILs and anti-PD1 significantly improves the prognosis of metastatic cervical cancer.

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