scholarly journals Acetyl Coenzyme A Synthase 2 Acts as a Prognostic Biomarker Associated with Immune Infiltration in Cervical Squamous Cell Carcinoma

Cancers ◽  
2021 ◽  
Vol 13 (13) ◽  
pp. 3125
Author(s):  
Chia-Jung Li ◽  
Yi-Han Chiu ◽  
Chung Chang ◽  
Yuan-chin Ivan Chang ◽  
Jim Jinn-Chyuan Sheu ◽  
...  

Cervical squamous cell carcinoma (CESC) is one of the most common malignant tumors in women worldwide with a low survival rate. Acetyl coenzyme A synthase 2 (ACSS2) is a conserved nucleosidase that converts acetate to acetyl-CoA for energy production. Our research intended to identify the correlations of ACSS2 with clinical prognosis and tumor immune infiltration in CESC. ACSS2 is highly expressed in many tumors and is involved in the progression and metastasis of these tumors. However, it is not clear how ACSS2 affects CESC progression and immune infiltration. Analysis of the cBioPortal, GEPIA2, UALCAN, and TCGA databases showed that ACSS2 transcript levels were significantly upregulated in multiple cancer types including CESC. Quantitative RT-PCR analysis confirmed that ACSS2 expression was significantly upregulated in human cervical cancer cells. Here, we performed tissue microarray analysis of paraffin-embedded tissues from 240 cervical cancer patients recorded at FIGO/TNM cancer staging. The results showed that ACSS2 and PDL1 were highly expressed in human CESC tissues, and its expression was associated with the clinical characteristics of CESC patients. TIMER database analysis showed that ACSS2 expression in CESC was associated with tumor infiltration of B cells, CD4+ and CD8+ T cells, and cancer-associated fibroblasts (CAF). Kaplan–Meier survival curve analysis showed that CESC with high ACSS2 expression was associated with shorter overall survival. Collectively, our findings establish ACSS2 as a potential diagnostic and prognostic biomarker for CESC.

2018 ◽  
Vol 13 (1) ◽  
pp. 527-532
Author(s):  
Qingyuan Lv ◽  
Weijuan Zhong ◽  
Xiabin Ye ◽  
Yang Lv ◽  
Haiying Liu ◽  
...  

AbstractObjectiveThe aim of this study was to evaluate the expression of Angiopoietin-1 (Ang-1), Angiopoietin-2 (Ang-2) and vascular endothelial growth factor (VEGF) in cervical cancer and its clinical significance.MethodsImmunohistochemical assay was used to examine the expression of Ang-1/2 and VEGF in tumor tissue from 56 cervical squamous cell carcinoma patients treated with operation only (SCC-O group), as well as 51 subjects with cervical squamous cell carcinoma treated with neoadjuvant radiotherapy (SCC-RCO group, n=28) or neoadjuvant chemotherapy (SCC-CO group, n=23). Both microvessel density (MVD) and lymphatic vessel density (LVD) were examined in the three groups through detection of CD34 and D2-40 expression in respective tissue samples.ResultsWith the progression of cervical cancer, the positive expression scores of Ang-2 and VEGF were significantly increased (p<0.05). Compared with surgical intervention, neoadjuvant chemoradiotherapy significantly reduced the positive expression scores of Ang-1, Ang-2, and VEGF in cervical cancer tissues (p<0.05). The MVD values of the SCC-CO and SCC-RO groups were significantly reduced as compared to the SCC-O group (p<0.05). Similarly, the LVD values of the SCC-CO and SCC-RO groups were also significantly reduced when compared to those of the SCC-O group (p<0.05). However, LVD values of the SCC-CO and SCC-RO groups were not statistical different (p>0.05).ConclusionAng-1, Ang-2 and VEGF may play an important role in the development of cervical cancer. Mutual synergism of Ang-2 and VEGF demonstrated a close relationship with the generation of cervical blood and lymphatic vessels. Cervical cancer radiotherapy and chemotherapy could significantly inhibit the formation of blood vessels and lymphatic vessels in tumor tissue.


2022 ◽  
Vol 12 ◽  
Author(s):  
Yu Wang ◽  
Weigang Gu ◽  
Weiwei Wen ◽  
Xiaofeng Zhang

Background: Serpin peptidase inhibitor clade H, member 1 (SERPINH1) is a gene encoding a member of the serpin superfamily of serine proteinase inhibitors. The upregulated of SERPINH1 was associated with poor prognosis in breast cancer, stomach adenocarcinoma, and esophageal carcinoma. However, the role of SERPINH1 in pan-cancer is largely unexplored.Methods: SERPINH1 expression and the correlation with prognosis in human pan-cancer were analyzed by the Cancer Genome Atlas and the Genotype-Tissue Expression dataset. Pearson correlation analysis was applied to evaluate the role of SERPINH1 expression in tumor mutation burden (TMB), microsatellite instability (MSI), mismatch repair (MMR), DNA methyltransferase, and common immunoregulators. Spearman’s correlation test was used to analysis SERPINH1 expression in tumor immune infiltration and infiltrating immune cells via the Tumor Immune Evaluation Resource database. Furtherly, immunohistochemistry staining of SERPINH1 was acquired from the Human Protein Atlas database for validation.Results: SERPINH1 was abnormally expressed in fourteen cancers. The high expression of SERPINH1 significantly reduced the overall survival (OS), disease-specific survival, and progression free interval in eleven cancers. Moreover, SERPINH1 expression was correlated with MMR, MSI, TMB, and DNA methylation in multiple types of cancer. Also, SERPINH1 expression showed strong association with immunoregulators and immune checkpoint markers in testicular germ cell tumors, brain lower grade glioma (LGG), pheochromocytoma and paraganglioma. In addition, SERPINH1 expression was related to immune cell infiltration in multiple cancers, particularly in breast invasive carcinoma, LGG, and liver hepatocellular carcinoma. The result of immunohistochemistry verification shown that SERPINH1 staining was higher in tumor samples than in normal tissue in colon adenocarcinoma, head and neck squamous cell carcinoma, kidney renal papillary cell carcinoma and cervical squamous cell carcinoma, which was consistent with the result of OS.Conclusion: Overall, these results indicate that SERPINH1 may serve as an important prognostic biomarker and correlate with tumor immunity in human pan-cancer.


2021 ◽  
Author(s):  
Yu Ran ◽  
Qiang Yi ◽  
Cong Li ◽  
Qin Zhou

Abstract Background: Combined cervical cancer and pelvic organ prolapse (POP) is extremely uncommon and there is no standard treatment guideline for the complex comorbidity. We attempted to provide a treatment strategy and explore possible reasons for the comorbidities.Case presentation: We presented a 62-year-old patient seeking treatment for postmenopausal tissue prolapse and leakage of urine. Physical examination revealed procidentia with a 2.5 cm papillary and erosive lesion that was pathologically confirmed as cervical squamous cell carcinoma in stage Ib2. Clinical diagnosis included cervical squamous cell carcinoma in stage Ib2, prolapse of the anterior and posterior walls of the vagina and uterine, stress urinary incontinence (SUI). Then she was performed radical surgery for cervical cancer and tension-free vaginal tape-obturator (TVT-O). The urine function was good after operation. The surgery solved two diseases, which improved the quality of life (QOL) of patient and radically cured cervical malignancies at the same time.Conclusions: Surgical-based treatment seems to be more suitable that can cure the two diseases and improve the QOL. We should pay attention to the potential high incidence of HPV infection and HPV-related cervical cancer so that we should not ignore the screening for cervical cancer in the prolapse group and initiate surgery treatment strategies of cervical cancer or pre-cancerous lesions as early as possible to reach an optimal outcome of patient.


Author(s):  
Joana Moreira-Barros ◽  
Kuan-Gen Huang ◽  
Tsung-Hsun Tsai

Objective To describe a case of radiation-induced uterine carcinosarcoma 6 years after a cervical squamous cell carcinoma treatment, which imposed some diagnostic and management challenges. Case Report A 57-year-old woman with a history of pelvic chemoradiotherapy ∼ 6.5 years before the event described in this study, following an International Federation of Gynecology and Obstetrics (FIGO) stage IIB cervical cancer, presented with a cervical mass, involving the uterine cavity, the cervical canal and the upper two thirds of the vagina. The biopsy showed a poorly differentiated carcinoma, and a positron emission tomography (PET) scan excluded distant metastasis, although it was unable to define the origin of the tumor as either a new primary malignancy of the endometrium/cervix or as a cervical recurrence. Surgical staging procedure was performed, and the diagnosis was endometrial carcinosarcoma, FIGO stage IIB. The patient was not able to complete the adjuvant therapy, and the progression of the disease was remarkable. Conclusion The present case highlights one of the less common but more serious consequences of radiotherapy for cervical cancer, which has an increasing incidence in younger women, raising concerns about the long-term consequences of its management.


2021 ◽  
Vol 18 (6) ◽  
pp. 8201-8222
Author(s):  
Caiyun Wu ◽  
◽  
Cong Ma ◽  
Jing Yuan ◽  
Pei Zhou ◽  
...  

<abstract> <p>Cervical cancer, as the second most common female malignancy, brings a great health burden to women worldwide. Cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC) are the most common histological subtypes of cervical cancer. CXC chemokines (CXCLs) within the tumor microenvironment can modulate carcinogenesis and progression. The present study aimed to explore the therapeutic and prognostic value of different CXCLs in CESC. ONCOMINE, GEPIA, cBioPortal, TRRUST, GeneMANIA, STRING and TIMER were utilized to explore the expression, mutation and function of CXCLs in CESC, as well as their correlation with pathological and survival features of CESC patients. We found that the mRNA expression levels of CXCL1/8/9/10/11/13/16/17 in CESC were upregulated compared with normal cervical tissues, whereas CXCL12 was downregulated. No significant correlation was found between the expression levels and pathological stage of CESC patients. CESC patients with high expression of CXCL1/2/3/4/5/8 were significantly associated with poor overall survival, additionally, low mRNA level of CXCL3 was associated with better disease-free survival. Besides, a high mutation rate (43%) of CXCLs in CESC was observed. Depicted by co-expression analysis, the expression of CXCL1/2/3/6/8 showed a modest to strong correlation, while that of CXCL9/10/11/13 showed a very strong correlation. Differentially expressed CXCLs primarily functioned in chemokine signaling pathway and inflammation response, such as cell chemotaxis, chemokine activity and chemokine receptor binding. We also found the association of CXCLs with the tumor-infiltration of six types of immune cells (B cells, CD8+ T cells, CD4+ T cells, macrophages, neutrophils and dendritic cells) in CESC patients. The present study elucidated that CXCLs may have the potential to be novel therapeutic targets and prognosis predictors of CESC patients.</p> </abstract>


2021 ◽  
Author(s):  
Yifang Mao ◽  
Run Chen ◽  
Meng Xia ◽  
Peng Guo ◽  
Feitianzhi Zeng ◽  
...  

Aim: To better predict the survival of cervical squamous cell carcinoma (CESC) patients, we aimed to construct a signature according to different immune infiltration. Methods: We downloaded the RNA sequences of CESC patients from the Cancer Genome Atlas database. By using single-sample gene set enrichment analysis, we separated the samples into high- and low-immunity groups. Then we separated the samples into training and testing datasets and performed the following analyses: univariate, least absolute shrinkage and selection operator analysis, multivariate Cox regression analyses and weighted gene coexpression network analysis using R software. Gene ontology and Kyoto Encyclopedia of Genes and Genomes studies were performed using the Database for Annotation, Visualization and Integrated Discovery website. Results & conclusion: We finally identified a signature with three mRNAs and two lncRNAs: ADGRG5, HSH2D, ZMAT4, RBAKDN and LINC00200. In short, our study constructed an mRNA–lncRNA signature related to immune infiltration to better predict the survival of CESC patients.


2018 ◽  
Vol 19 (11) ◽  
pp. 3607 ◽  
Author(s):  
Xia Li ◽  
Yunpeng Cai

Cervical cancer is traditionally classified into two major histological subtypes, cervical squamous cell carcinoma (CSCC) and cervical adenocarcinoma (CA). However, heterogeneity exists among patients, comprising possible subpopulations with distinct molecular profiles. We applied consensus clustering to 307 methylation samples with cervical cancer from The Cancer Genome Atlas (TCGA). Fisher’s exact test was used to perform transcription factors (TFs) and genomic region enrichment. Gene expression profiles were downloaded from TCGA to assess expression differences. Immune cell fraction was calculated to quantify the immune cells infiltration. Putative neo-epitopes were predicted from somatic mutations. Three subclasses were identified: Class 1 correlating with the CA subtype and Classes 2 and 3 dividing the CSCC subtype into two subclasses. We found the hypomethylated probes in Class 3 exhibited strong enrichment in promoter region as compared with Class 2. Five TFs significantly enriched in the hypomethylated promoters and their highly expressed target genes in Class 3 functionally involved in the immune pathway. Gene function analysis revealed that immune-related genes were significantly increased in Class 3, and a higher level of immune cell infiltration was estimated. High expression of 24 immune genes exhibited a better overall survival and correlated with neo-epitope burden. Additionally, we found only two immune-related driver genes, CARD11 and JAK3, to be significantly increased in Class 3. Our analyses provide a classification of the largest CSCC subtype into two new subclasses, revealing they harbored differences in immune-related gene expression.


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