Cervical Cancer Metastasis Research Articles

A novel lymphatic pattern promotes metastasis of cervical cancer in a hypoxic tumour-associated macrophage-dependent manner

Lymphatic remodelling in the hypoxic tumour microenvironment (TME) is critically involved in the metastasis of cervical squamous cell carcinoma (CSCC); however, its underlying mechanisms remain unclear. Here, we uncovered a novel lymphatic pattern in the hypoxic TME, wherein lymphatic vessels (LVs) are encapsulated by tumour-associated macrophages (TAMs) to form an interconnected network. We describe these aggregates as LVEM (LVs encapsulated by TAMs) considering their advantageous metastatic capacity and active involvement in early lymph node metastasis (LNM). Mechanistic investigations revealed that interleukin-10 (IL-10) derived from hypoxic TAMs adjacent to LVs was a prerequisite for lymphangiogenesis and LVEM formation through its induction of Sp1 upregulation in lymphatic endothelial cells (LECs). Interestingly, Sp1high LECs promoted the transactivation of C–C motif chemokine ligand 1 (CCL1) to facilitate TAM and tumour cell recruitment, thereby forming a positive feedback loop to strengthen the LVEM formation. Knockdown of Sp1 or blockage of CCL1 abrogated LVEM and consequently attenuated LNM. Notably, CSCCnon-LNM is largely devoid of hypoxic TAMs and the resultant LVEM, which might explain its metastatic delay. These findings identify a novel and efficient metastasis-promoting lymphatic pattern in the hypoxic TME, which might provide new targets for anti-metastasis therapy and prognostic assessment.

Integrated Profiles Analysis Identified a Coding-Non-Coding Signature for Predicting Lymph Node Metastasis and Prognosis in Cervical Cancer.

Accumulating evidence has shown that lymph node metastasis (LNM) is not only an important prognostic factor but also an indicator of the need for postoperative chemoradiotherapy. Therefore, identifying risk factors or molecular markers related to LNM is critical for predicting the prognosis and guiding individualized treatment of patients with cervical cancer. In this study, we used the machine learning-based feature selection approach to identify eight optimal biomarkers from the list of 250 differentially expressed protein-coding genes and long non-coding RNAs (lncRNAs) in the TCGA cohort. Then a coding-non-coding signature (named CNC8SIG) was developed using the elastic-net logistic regression approach based on the expression levels of eight optimal biomarkers, which is useful in discriminating patients with LNM from those without LNM in the discovery cohort. The predictive performance of the CNC8SIG was further validated in two independent patient cohorts. Moreover, the CNC8SIG was significantly associated with patient’s survival in different patient cohorts. In silico functional analysis suggested that the CNC8SIG-associated mRNAs are enriched in known cancer-related biological pathways such as the Wnt signaling pathway, the Ras signaling pathway, Rap1 signaling pathway, and PI3K-Akt signaling pathway.

Long noncoding RNA TPT1-AS1 promotes the progression and metastasis of colorectal cancer by upregulating the TPT1-mediated FAK and JAK-STAT3 signalling pathways.

Tumour protein translationally controlled 1 (TPT1) antisense RNA 1 (TPT1-AS1) is known to be involved in the development and metastasis of cervical and ovarian cancers; however, its biological role in colorectal cancer (CRC) remains unknown. This study aimed to determine the function and mechanism of action of TPT1-AS1 in the progression and metastasis of CRC. Elevated TPT1-AS1 levels were observed in CRC tissues. Furthermore, the high expression levels were found to be correlated with unfavourable clinicopathological characteristics in CRC. Cell function experiments demonstrated that TPT1-AS1 depletion impeded cell proliferation, migration and invasion and enhanced cell adhesion; it also attenuated tumorigenesis and metastasis in vivo. Additionally, TPT1-AS1 was predominately located in the nuclei of the cells and could upregulate the expression of TPT1 by recruiting mixed lineage leukaemia protein-1 (MLL1), which increased the trimethylation of H3K4 me3 in the TPT1 promoter region and subsequently activated FAK and JAK-STAT3 signalling cascades. The inhibition of FAK activation by PF573228 significantly attenuated the oncogenic effect of TPT1-AS1. These findings indicated that TPT1-AS1 promoted tumour progression and metastasis in CRC by upregulating TPT1 levels and activating the FAK and JAK-STAT3 signalling pathways. Thus, TPT1-AS1 may be considered as a potential therapeutic target for CRC.

A novel 2-deoxy-2-fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT)-based nomogram to predict lymph node metastasis in early stage uterine cervical squamous cell cancer.

We aimed to establish an effective 2-deoxy-2-fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) based nomogram for pelvic lymph node (PLN) metastasis prediction in early-stage uterine cervical squamous cell cancer. A predictive model was developed in a cohort that consisted of 351 patients with stage IB-IIA [International Federation of Gynecology and Obstetrics (FIGO) 2009] uterine cervical squamous cell cancer. All patients underwent a preoperative PET/CT scan and subsequent radical surgery between 2010 and 2017, with 241 and 110 patients allotted into training and external validation cohorts. The chi-square (χ2) test and the logistic regression analysis were used to compare the clinical and PET/CT parameters with PLN metastasis. A nomogram was developed and validated by internal and external validation. In the training cohort, 82 (34.0%) patients had positive PLNs identified in the preoperative PET/CT scan. Among them, 46 (56.1%) were pathologically confirmed. There were 30 (18.9%) PET/CT scan-negative patients found to have PLN metastasis. The χ2 test and logistic regression showed that only the squamous cell carcinoma antigen (SCCA) level (P=0.039) and maximum standardized uptake value (SUVmax) of PLN (nSUVmax, P=0.001) were independent predictors for PLN metastasis. A predictive nomogram based on these 2 parameters was developed with a C-index [95% confidence interval (CI)] of 0.854 (0.772-0.937) on internal validation and 0.836 (0.723-0.948) on the external validation. Compared to nSUVmax alone, our nomogram showed elevated sensitivity (70.5%, 73.1% vs. 60.5%), specificity (94.4%, 86.4% vs. 78.2%), and positive predictive value (PPV) (93.9%, 86.4% vs. 56.1%) in both the training and validation cohorts. We successfully developed a noninvasive and convenient nomogram for preoperative identification of PLN metastasis in early-stage squamous cell cervical cancer.

MiR-29c-3p inhibits epithelial-mesenchymal transition to inhibit the proliferation, invasion and metastasis of cervical cancer cells by targeting SPARC.

BackgroundCervical cancer is one of the most common gynecological malignancies. Cancer recurrence and the poor efficacy of cervical cancer treatments are mainly caused by invasion and metastasis of cervical cancer cells. This study is to investigate whether miR-29c-3p can inhibit epithelial-mesenchymal transition (EMT) by targeting secreted protein acidic and rich in cysteine (SPARC), thus inhibiting the invasion and metastasis of human cervical cancer cells.MethodsThe expression levels of miR-29c-3p and SPARC in cervical cancer tissues and non-tumor adjacent tissues, human normal cervical epithelial cell line Ect1/E6E7 and human cervical cancer cell lines HeLa, CaSki, C-33A, HT-3 and SiHa were detected. After the expression of miR-29c-3p and SPARC was intervened in C-33A and SiHa cells, RT-qPCR was used to detect the expression levels of miR-29c-3p and SPARC. Western blot was performed to observe the expression levels of SPARC and EMT-related proteins. The proliferation rate of C-33A and SiHa cells was measured using an MTT assay. The viability of the cells was determined using a cell colony formation assay. Apoptosis and cell cycle was measured using flow cytometry, and migration ability was observed using a wound healing assay. A transwell invasion assay was used to determine the invasion ability of the cells, whilst a dual-luciferase reporter assay verified that SPARC was a target gene of miR-29c-3p.ResultsmiR-29c-3p was expressed at low levels in cervical cancer tissues and cells, while SPARC expression was upregulated. The luciferase reporter assay confirmed that miR-29c-3p targeted and bound to SPARC. MiR-29c-3p overexpression significantly inhibited the proliferation, invasion, migration, and cell cycle of cervical cancer cells, but promoted apoptosis. In the miR-29c-3p group (miR-29c-3p overexpression), EMT progression was inhibited by upregulating E-cadherin expression and downregulating N-cadherin, vimentin, and Snail expression, which was contrary to the results of the in-miR-29c-3p group (inhibition of miR-29c-3p expression). In the miR-29c-3p + SPARC group (miR-29c-3p overexpression + SPARC overexpression), the effect of miR-29c-3p overexpression on cervical cancer cell functions was reversed.ConclusionsmiR-29c-3p can inhibit EMT by targeting SPARC, so as to inhibit the invasion and metastasis of cervical cancer cells.

Clinico-Pathologic Factors Affecting Lymph Node Metastases in Cervical Cancer

Clinico-Pathologic Factors Affecting Lymph Node Metastases in Cervical Cancer

Cervical Cancer Metastasis and Recurrence Risk Prediction Based on Deep Convolutional Neural Network

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MiR-552 promotes the proliferation and metastasis of cervical cancer cells through targeting MUC15 pathway.

Accumulating evidence shows that microRNAs (miRNAs) play key roles in tumorigenesis, progression, recurrence and drug resistance of malignant tumors. The tumor-promoting role of miR-552 has been evidenced in multiple tumors. Yet, the relevance of miR-552 in cervical cancer remains undetermined. This study aimed to investigate the role of miR-552 in cervical cancer proliferation and metastasis. Herein, we for first found that miR-552 expression was upregulated in cervical cancer tissues compared with their normal controls. Functional assays revealed that miR-552 promoted the proliferation and metastasis of cervical cancer cells. Mechanically, bioinformatics and luciferase reporter analysis identified MUC15 as a direct target of miR-552. Reduced MUC15 expression was detected in cervical cancer, and MUC15 overexpression exhibited a tumor-suppressive effect. MUC15 restoration partially abolished the discrepancy of growth and metastasis capacity between miR-552 overexpression cervical cancer cells and control cells. Taken together, these data demonstrate that miR-552 acts as a potential oncogene miRNA in cervical cancer, which exerts its function through targeting MUC15.

Circ SMARCA5 Inhibited Tumor Metastasis by Interacting with SND1 and Downregulating the YWHAB Gene in Cervical Cancer

Cervical cancer is one of the diseases that seriously endanger women’s health. Circular RNA plays an important role in regulating the occurrence and development of cervical cancer. Here, we investigated the mechanisms of circ SMARCA5 in the development of cervical cancer. Quantitative reverse transcriptase polymerase chain reaction (RT-qPCR) results showed that the expression of SMARCA5 was downregulated in cervical cancer tissues and cell lines. Then we found that overexpression of SMARCA5 inhibited proliferation and invasion, but promoted apoptosis in cervical cancer cells. These were detected by Cell Counting Kit-8, Transwell, and Annexin V-fluorescein isothiocyanate/propidium iodide detection kit, respectively, and the expression of the apoptosis-related proteins was determined by western blotting. Then we predicted that SMARCA5 combined with Staphylococcal nuclease domain-containing 1 (SND1) by starBase, and verified by RNA pull-down assay. To further reveal the molecular mechanisms of SMARCA5 in the progression of cervical cancer, the interaction protein of SND1 was predicted by STRING, and the interaction was verified by co-immunoprecipitation assay. Then, the effects of SND1 or YWHAB on the development of cervical cancer were detected by the gain and loss function test, and we found that knockdown of SND1 or YWHAB reversed the effects of SMARCA5 short interfering RNA on proliferation, invasion, and apoptosis of cervical cancer cells. Overexpression of SMARCA5 inhibited cervical cancer metastasis in vivo. Our results showed that overexpression of circ SMARCA5 inhibits the binding of SND1 to YWHAB, and inhibits the proliferation and invasion, but promotes apoptosis in cervical cancer cells, thus inhibiting the metastasis of cervical cancer.

Protein tyrosine phosphatase, receptor type B is a potential biomarker and facilitates cervical cancer metastasis via epithelial-mesenchymal transition

ABSTRACT Cervical cancer (CC) is one of the most common malignant tumors. This study analyzed the impact of protein tyrosine phosphatase, receptor type B (PTPRB) on malignant behavior of CC and explored its possible molecular mechanism. RT-PCR, western blot and Immunohistochemistry were applied to examine the expression of PTPRB in CC specimens and cells. Aberrant PTPRB expression in CC and survival outcomes were constructed using The Cancer Genome Atlas (TCGA) database and tissue microarray cervical squamous cell carcinoma cohort. Cultured human CC cells were assayed for viability, apoptosis, migration, and invasion in vitro and in vivo. Kyoto Encyclopedia of Genes and Genomes (KEGG) assays and gene set enrichment analysis (GSEA) assays were used to delve into PTPRB-related pathways using TCGA datasets. The levels of proteins associated with the epithelial–mesenchymal transition (EMT) pathway and modulated by PTPRB were examined through Western blot. We found that the levels of PTPRB in CC tissues and cells were distinctly up-regulated. PTPRB was also an unfavorable prognostic factor for CC patients. Functionally, PTPRB knockdown exhibits tumor-suppressive function via reducing cell proliferation and metastasis and inducing cell apoptosis. KEGG assays and GSEA assays suggested PTPRB overexpression was associated with several tumor-related pathways. The results of Western blot assays suggested that N-cadherin was decreased in the PTPRB-knockdown CC cells, while E-cadherin was increased. Overall, PTPRB is highly expressed in CC and can effectively enhance the proliferation, metastasis and EMT process of tumor cells. PTPRB is expected to be a therapeutic target for CC.

Predictive value of protease-activated receptor-2 (PAR2 ) in cervical cancer metastasis.

Metastasis is the primary cause of an unfavourable prognosis in patients with malignant cancer. Over the last decade, the role of proteinases in the tumour microenvironment has attracted increasing attention. As a sensor of proteinases, proteinase‐activated receptor 2 (PAR2) plays crucial roles in the metastatic progression of cervical cancer. In the present study, the expression of PAR2 in multiple types of cancer was analysed by Gene Expression Profiling Interactive Analysis (GEPIA). Kaplan‐Meier plotter was used to calculate the correlation between survival and the levels of PAR2, Grb‐associated binding protein 2(Gab2) and miR‐125b. Immunohistochemistry (IHC) was performed to examine PAR2 expression in a tissue microarray (TMA) of CESCs. Empower Stats was used to assess the predictive value of PAR2 in the metastatic potential of CESC. We found that PAR2 up‐regulation was observed in multiple types of cancer. Moreover, PAR2 expression was positively correlated with the clinicopathologic characteristics of CESC. miR‐125b and its target Gab2, which are strongly associated with PAR2‐induced cell migration, are well‐characterized as predictors of the prognostic value of CESC. Most importantly, the Cancer Genome Atlas (TCGA) data set analysis showed that the area under the curve (AUC) of the PAR2 model was significantly greater than that of the traditional model (0.833 vs 0.790, P < .05), demonstrating the predictive value of PAR2 in CESC metastasis. Our results suggest that PAR2 may serve as a prognostic factor for metastasis in CESC patients.

RETRACTED: Long non-coding RNA TUG1 sponges microRNA-381-3p to facilitate cell viability and attenuate apoptosis in cervical cancer by elevating MDM2 expression

Based on the theory that long non-coding RNAs (lncRNAs) sponge microRNAs (miRNAs) to engage in cervical cancer development, this work was set out to investigate the possible role of lncRNA taurine upregulated gene 1 (TUG1) and miR-381-3p in the development of cervical cancer. TUG1, miR-381-3p and murine double minute 2 (MDM2) expression were measured in cervical cancer tissues and cells. The nexus between TUG1 and clinicopathological features of cervical cancer was discussed. The biological functions of TUG1, miR-381-3p and MDM2 on cervical cancer cell process were interpreted via gain- and loss-of-function experiments. Also, tumor xenograft in nude mice was conducted in vivo. The interactions between TUG1, miR-381-3p and MDM2 were identified. TUG1 and MDM2 raised while miR-381-3p reduced in cervical cancer. TUG1 expression was related to tumor size, differentiation, international federation of gynecology and obstetrics stage and lymph node metastasis of cervical cancer. Restored miR-381-3p, depleted TUG1 or reduced MDM2 decreased viability, colony-forming, migration and invasion abilities, and facilitated apoptosis of cervical cancer cells. Xenografted tumors grew slowly upon injection with restored miR-381-3p and depleted TUG1. TUG1 bound to miR-381-3p and miR-381-3p targeted MDM2. On all accounts, this present study provides evidence that silencing TUG1 depressed cervical cancer cell progression through miR-381-3p/MDM2 axis, highlighting a theoretical basis for cervical cancer treatment.

MiR‑34c‑5p targets Notch1 and suppresses themetastasis and invasion of cervical cancer.

Micro (mi)RNAs are crucial participants in the progression of cervical cancer (CC). Growing evidence indicates that miRNA (miR)-34c-5p is a pivotal tumor suppressor in numerous types of cancer and its functions in CC require further investigating. The present study demonstrated that there was a decreased level of miR-34c-5p in CC-associated cell lines compared with healthy control samples. It also demonstrated that miR-34c-5p targeted Notch1 and suppressed CC progression. Dual-Luciferase reporter assays verified the targeted relationship of miR-34c-5p and Notch1. The expression of Notch1 in HeLa cells was markedly reduced following miR-34c-5p overexpression and the proliferation, migration and invasion of HeLa cells were reduced although apoptosis was accelerated. However, overexpression of miR-34c-5p was reversed following the addition of Notch1, which supported the finding of the targeted relationship between miR-34c-5p and Notch1. Flow cytometry demonstrated that miR-34c-5p inhibited the proliferation of HeLa cells while accelerating apoptosis. The present study concluded that miR-34c-5p was a tumor suppressor in CC and may be a novel measure for the future treatment of CC.

Circular RNA circGSE1 Promotes Cervical Cancer Progression Through miR-138-5p/Vimentin

BackgroundA growing number of studies have identified that circular RNAs (circRNAs) play a vital role in the progression of various tumors. However, the underlying functions and mechanisms of circRNAs in cervical cancer have not been clarified.MethodsqRT-PCR was used to detect the level of circGSE1 in cervical cancer tissues and matched normal tissues. In vitro cell wound healing, transwell migration and invasion assays were employed to assess the effects of circGSE1 on cell mobility. The pull-down, luciferase reporter, RIP and rescue assays were performed to evaluate the interaction between circGSE1and miR-138-5p and the regulation of miR-138-5p on Vimentin.ResultsWe found that circGSE1 was significantly higher in cervical cancer tissues than that in matched normal tissues. Further analyses revealed that the level of circGSE1 was positively correlated with tumor differentiation, FIGUREO stage, depth of stromal invasion, lymph node metastasis and infiltration of parauterine organ. Kaplan–Meier survival analysis showed that high circGSE1 predicted worse overall survival and disease-free survival. Down-regulated circGSE1 evidently inhibited cell migration and metastasis of cervical cancer, while up-regulated circGSE1 significantly promoted cell migration and metastasis. The pull-down, luciferase reporter and RIP assays revealed that circGSE1 directly bound to and sponge miR-138-5p. MiR-138-5p inhibited the expression of Vimentin through directly binding to 3ʹUTR of Vimentin mRNA. In addition, miR-138-5p suppressed cell migration and invasion through inhibiting Vimentin expression, and circGSE1 promoted cell migration and invasion through sponging miR-138-5p and enhancing Vimentin expression.ConclusionCircGSE1 promotes the progression and may act as a novel diagnostic biomarker for disease progression of cervical cancer.

Anti-pulmonary metastases from cervical cancer responses induced by a human papillomavirus peptide vaccine adjuvanted with CpG-oligodeoxynucleotides in vivo

Metastasis, particularly hematogenous metastasis, is associated with poor prognosis in patients with cervical cancer. The lungs are the most common site for hematogenous metastasis of cervical cancer. The currently available therapeutic modalities, including surgery, radiotherapy, or chemotherapy do not provide satisfactory clinical outcome for patients with pulmonary metastases. Therefore, it is necessary to investigate an alternative efficacious treatment modality. Therapeutic vaccines may evoke tumor-specific immune responses in patients to attack tumor cells, representing an attractive treatment option for controlling metastatic tumors. Our previous study demonstrated that a single administration of a human papillomavirus 16 E7 peptide vaccine, adjuvanted with unmethylated CpG-oligodeoxynucleotides, induced the clearance of subcutaneous xenograft cervical cancer. In this study, we investigated the anti-metastases responses induced by this vaccine using a murine model of pulmonary metastases from cervical cancer. The results showed that subcutaneous administration of the vaccine inhibited the growth of pulmonary metastases, which may be attributed to the increased infiltration of CD4 + and CD8 + T cells, and decreased number of immunosuppressive cells (including myeloid-derived suppressive cells and tumor-associated macrophages) in the lungs. Meanwhile, the alteration in a panel of cytokines, chemokines, and matrix metalloproteinases induced by the vaccination may contribute to the re-modulation of the local suppressive environment and inhibition of pulmonary metastases. To the best of our knowledge, this is the first report on the efficacy of the vaccine formula against murine pulmonary metastases from cervical cancer.

MiR-362 suppresses cervical cancer progression via directly targeting BAP31 and activating TGFβ/Smad pathway.

BAP31 (B‐cell receptor‐associated protein 31) is an important regulator of intracellular signal transduction and highly expressed in several cancer tissues or testicular tissues. Our previous study had revealed that elevated BAP31 plays a crucial role in the progress and metastasis of cervical cancer. Even so, the precise mechanism of abnormal BAP31 elevation in cervical cancer has not been fully elucidated. We revealed that the expression of BAP31 was mainly regulated by microRNA‐362 (miR‐362), which was markedly downregulated in cervical cancer tissues and negatively correlated with clinical tumor staging. Overexpression of miR‐362 inhibited cervical cancer cell proliferation and increased the proportion of apoptotic cells. Furthermore, miR‐362 reduced the tumor sizes and prolonged mice survival time in xenograft nude mice model. Finally, we demonstrated that the BAP31/SPTBN1 complex regulated tumor progression through the Smad 2/3 pathway under the control of miR‐362. Collectively, our findings demonstrated that miR‐362 could work as an anti‐oncomiR that inhibits proliferation and promotes apoptosis in cervical cancer cells via BAP31 and TGFβ/Smad pathway. Overexpression of miR‐362 might be a potential therapeutic strategy for cervical cancer.

The Rare Occurrence of Splenic Metastasis of Cervical Cancer: A Case Report

Splenic metastasis of solid tumors has a low occurrence rate and an incidence of only 2.9%–9%. Given its rarity, only a few cases of splenic metastasis of cervical cancer have been reported. This report presents a case of 76-year-old woman with stage IB1, moderately differentiated adenocarcinoma of cervix, coupled with invasion of cervical stroma and cervical canal. The patient had a cancer antigen 125 (CA-125) level of 150 U/ml and was treated with hysterictomy and pelvic lymphadenectomy. She received 45 Gy pelvic radiotherapy and then 24 Gy brachytherapy. She developed abdominal pain two years later. Computed tomography (CT) examination found two solid lesions of the spleen and no lesions in the rest of the abdominal cavity and chest. Her CA-125 level increased to 2,733 U/ml. Histopathological findings showed splenic metastasis of well differentiated adenocarcinoma in cervix. Immunohistochemical tests revealed that the tumor was positive for carcinoembryonic antigen and negative for estrogen and progesterone receptors. Eight weeks after operation, CA-125 level of the patient was 16 U/ml. She received adjuvant therapy consisting of paclitaxel and cisplatin for 6 cycles. After being followed up for 12 months, the patient was still alive and had no evidence of tumor activity. The spleen is a rare metastatic site. Splenectomy is considered an appropriate treatment to prevent complications, such as splenic rupture and splenic vein thrombosis, and reduce the pain caused by splenomegaly.

LINC00636 promotes lymph node metastasis and cervical cancer through targeting NM23.

Background: Metastasis is a major obstacle in treatment of cervical cancer, and long non-coding RNA (lncRNA) mediated regulatory effect on associated genes expression is found to be involved in metastasis. However, its mechanisms have not been fully elucidated.Materials and methods: Specimens from patients with cervical cancer metastasis and non-metastasis were used to screen out candidate non-coding RNAs (ncRNAs) and possible downstream targets. And then, effects were determined in vitro and in vivo through knockdown and overexpression techniques.Results: LINC00636 was significantly higher in serum and solid tumor cells of metastatic cervical cancer patients than non-metastatic patients. And knockdown of LINC00636 significantly suppressed invasion, proliferation of cervical cancer cells. NM23 expression was negatively regulated by LINC00636 and it mediated anti-tumor effects was partially blocked by overexpression of LINC00636.Conclusion: LINC00636 might promote metastasis of cervical cancer cells through inhibiting NM23 expression.

Circular RNA circ_PVT1 induces epithelial-mesenchymal transition to promote metastasis of cervical cancer.

Cervical cancer is one of the most common gynecological malignant tumors. At present, it has been confirmed that the occurrence and development of cervical cancer is related to human papillomavirus infection. As a new regulatory molecule and research hotspot, circRNA is abnormally expressed in tumors and other diseases, and is expected to become a new biomarker for diagnosis and prediction of tumor occurrence and development. In this research, bioinformatics analysis and RT-PCR analysis showed that hsa_circ_0009143 (circRNA_PVT1) was up-regulated in cervical cancer. Knockdown of circRNA_PVT1 inhibits the migration and invasion of cervical cancer cells and would prevent pulmonary metastasis. Overexpression of circRNA_PVT1 induced migration and invasion of cervical cancer cells, which would result in the promotion of pulmonary metastasis. Finally, we found that circRNA_PVT1 can induce EMT of cervical cancer cells via targeting miR-1286 by exosome pathway, which can be a novel mechanism of cervical cancer progression.

Radiotherapy for Cervical Cancer in Patients With Systemic Lupus Erythematosus

The use of radiation for cervical cancer in patients with systemic lupus erythematosus (SLE) has been rarely reported. We reported the experience of our hospital using intensity modulated radiation therapy (IMRT) for those patients. Medical records of 12 patients with SLE, who had received radiation due to cervical cancer in our hospital from May 2013 to June 2019, were retrospectively reviewed. Adverse events were graded in accordance with Common Terminology Criteria for Adverse Events v4.0. Survival data were analyzed with Kaplan-Meier method. 12 patients were diagnosed with cervical cancer in 2.6 to 18.6 years (mean time, 9.1y) following the onset of SLE in our hospital from May 2013 to June 2019. The median age at the diagnosis of SLE ranged from 18 to 68 years old (median, 36y). Concurrent chemoradiotherapy was delivered in 4 patients with IIB disease and 3 patients with IIIB disease. 2 patients with FIGO IA disease and 2 patients with IB disease received radical surgery and adjuvant radiation. For radical chemoradiotherapy, patients were treated with IMRT and brachytherapy with concurrent platinum-based chemotherapy (40 mg/m2). A total dose of 50.4Gy in 28 fractions was delivered to pelvic region, with a concomitant boost of involved lymph nodes to a dose of 60.2Gy. High-dose rate brachytherapy was delivered to a total dose of 28 to 30Gy in 5 fractions. For adjuvant radiation after surgery, a total dose of 45 to 50.4Gy in 25-28 fractions was prescribed. Before the treatment of radiotherapy, patients were evaluated for the SLE disease activity. All patients were in remission status with maintaining low to moderate dosage of prednisone (2.5 to 20mg per day) or immunosuppressive medication. The median follow-up was 31 months (range, 9.3 to 101m) from the diagnosis of cervical cancer. At last follow-up, 1 patient of concurrent chemoradiotherapy and 1 patient of post-surgery radiation died due to distant metastasis of cervical cancer. 10 patients remained complete remission. The 3-year overall survival rates (OS) and progression-free survival rates (PFS) were 77.8% and 83.3%, respectively. 8 (66.7%) of 12 patients experienced acute gastrointestinal toxicity of Grade 1 or Grade 2, and 2 (16.7%) patients had Grade 3 acute gastrointestinal toxicity. 6 (50%) patients experienced Grade 3 or Grade 4 acute hematologic toxicity during radiation. 2 (16.7%) patients had late Grade 1 gastrointestinal and urological toxicities. Only 1 patient had Grade 3 late hematologic toxicity. No other Grade 3 or greater radiation-related toxicities were revealed. The use of IMRT in SLE patients with cervical cancer provided a favorable outcome. And the risk of acute and chronic toxicity of radiation even with concurrent chemotherapy was moderate in SLE patients with remission status. The tolerance of SLE patients to radiotherapy may be achieved by IMRT technology and the satisfactory control of SLE disease activity, although further confirmatory studies are required.