Cervical Cancer Invasion Research Articles

CDKN2A inhibits cell proliferation and invasion in cervical cancer through LDHA-mediated AKT/mTOR pathway.

The current study aims to explore the effects of CDKN2A on cell proliferation and cycle, and investigate the underlying mechanisms. Expression of CDKN2A in cervical cancer cell lines was evaluated by real-time quantitative PCR (RT-qPCR) and western blotting. Apoptotic rate was detected by Annexin V assay. MTT assay, Transwell assay and cell cycle assay kit were applied to examine the effect of CDKN2A on cell viability, invasion and cell cycle. Co-immunoprecipitation and western blotting were devoted to explore the mechanism by which CDKN2A contributes to cell function. CDKN2A was expressed at a low level in cervical cancer cell lines. Overexpression of CDKN2A inhibited cell proliferation and invasion, and caused cell cycle arrest in the G1 phase. CDKN2A mediates the AKT-mTOR signaling pathway by suppressing lactate dehydrogenase (LDHA). Taken together, our data revealed that CDKN2A can be applied as a therapeutic target for the treatment of cervical cancer in future. CDKN2A inhibits cell proliferation and invasion in cervical cancer through LDHA-mediated AKT-mTOR pathway.

MiR‑802 inhibits the epithelial‑mesenchymal transition, migration and invasion of cervical cancer by regulating BTF3.

MicroRNA (miR)-802 has been discovered to be involved in the occurrence and development of numerous types of tumor; however, studies into the role of miR-802 in cervical cancer are limited. Therefore, the present study aimed to investigate the regulatory effects of miR-802 in cervical cancer cells. miR-802 expression levels in cervical cancer tissue and cells were analyzed using reverse transcription-quantitative (RT-q)PCR, a dual-reporter luciferase activity assay was used to identify the direct target gene of miR-802, and RT-qPCR and western blotting were performed to determine the relationship between miR-802 and basic transcription factor 3 (BTF3). Cell viability, and migration and invasion were analyzed using Cell Counting Kit-8 and Transwell assays, respectively. Finally, the expression levels of metastasis-associated proteins, N-cadherin and E-cadherin, were determined using RT-qPCR and western blotting. Decreased expression levels of miR-802 were found in cervical cancer tissues and cells, and the overexpression of miR-802 inhibited cell viability, migration and invasion. Moreover, miR-802 was discovered to directly target BTF3 to inhibit its expression. Notably, the overexpression miR-802 markedly reversed the promotive effect of BTF3 on cell viability, in addition to the migratory and invasive abilities of the cells. Simultaneously, the overexpression of miR-802 significantly suppressed epithelial-mesenchymal transition, and the expression levels of matrix metallopeptidase (MMP)2 and MMP9 in cells through regulating BTF3. In conclusion, the present study revealed that miR-802 may suppress cervical cancer progression by decreasing BTF3 expression levels, indicating that it may represent a potential therapeutic target for the treatment and prognosis of patients with cervical cancer.

MicroRNA-362-3p Inhibits Migration and Invasion via Targeting BCAP31 in Cervical Cancer.

Cervical cancer (CC) is the most common malignant tumor in gynecology, and metastasis is an important cause of patient death. MiRNAs (microRNAs) have been found to play key roles in cervical cancer metastasis, but the effect of miR-362-3p in CC is unclear. This study aimed to investigate the role of miR-362-3p in cervical cancer migration and invasion. We compared the expression levels of miR-362-3p in cervical cancer tissues and adjacent normal cervical tissues. In CC tissues, miR-362-3p expression was significantly down-regulated, which is related to the cancer stage and patient survival. MiR-362-3p can effectively inhibit the migration and invasion of cervical cancer cells. The dual-luciferase reporter assay results showed that BCAP31 (B cell receptor associated protein 31) is a direct target protein of miR-362-3p. The results of the immunohistochemical examination of clinical tissue samples showed that BCAP31 was abnormally highly expressed in cervical cancer, which was positively correlated with the clinical stage. BCAP31 knockdown exerted similar effects as miR-362-3p overexpression. Further GSEA analysis showed that BCAP31 may participate in multiple biological processes, such as protein transport, metabolism, and organelle organization. Our results suggest that miR-362-3p inhibits migration and invasion via directly targeting BCAP31 in cervical cancer, and restoring miR-362-3p levels may be a new treatment strategy for cervical cancer in the future.

Influence of uterine corpus invasion on prognosis in stage IA2–IIB cervical cancer: A multicenter retrospective cohort study

ObjectiveTo determine the associations between the presence and depth of uterine corpus invasion and survival in patients with cervical cancer. MethodsClinical data of patients with stage IA2–IIB cervical cancer who underwent radical hysterectomy between 2004 and 2016 were retrospectively reviewed. Uterine corpus invasion was identified from a review of uterine pathology. Independent prognostic factors for 5-year disease-free survival (DFS) and overall survival (OS) were identified using multivariate forward stepwise Cox proportional hazards regression models. ResultsA total of 1414 patients with stage IA2–IIB cervical cancer from 11 medical institutions in China were included. Retrospective review of the original pathology reports revealed a missed diagnosis of uterine corpus invasion in 38 (13.4%) patients and a misdiagnosis in 20 (1.8%) patients. Therefore, 284 patients with cervical cancer and uterine corpus invasion (90 [31.7%] patients had endometrial invasion, 105 [37.0%] patients had myometrial invasion <50%, and 89 [31.3%] patients had myometrial invasion ≥50%), and 1130 patients with cervical cancer without uterine corpus invasion were included in the analysis. The 5-year DFS and OS were significantly shorter for patients with uterine corpus invasion compared to patients with no uterine corpus invasion. Myometrial invasion ≥50% was an independent prognostic factor associated with decreased 5-year DFS (aHR, 2.307, 95% CI, 1.588–3.351) and 5-year OS (aHR, 2.736, 95% CI, 1.813–4.130), while myometrial invasion <50% or endometrial invasion had no effect on patient outcomes. ConclusionsDiagnosis of uterine corpus invasion is frequently missed. Myometrial invasion ≥50% within the uterine corpus was an independent factor associated with worse prognosis in patients with cervical cancer, while myometrial invasion <50% or endometrial invasion had no effect on outcomes.

Preliminary study of the clinical value of colposcopy in diagnosing vagina invasion in cervical cancer

Objective: To explore the preliminary clinical values of colposcopy in the diagnosis of vaginal invasion in cervical cancer. Methods: A retrospective review of the clinical records of patients (31 cases) with cervical cancer treated in Xuzhou Cancer Hospital from April 2015 to August 2019. For those with early-stage cervical cancer and the vagina invasion being difficult to be determined, those with advanced cervical cancer and the scope of vaginal invasion being difficult to be judged, and those with obvious vaginal tumor and underexposed cervix or inconspicuous cervical lesion and the primary location needing to be identified, colposcopy-guided vaginal and cervix biopsy were performed before treatment. Results: (1) Image characteristics of colposcopy and pathological diagnosis: among 31 cases, 30 of them had the similar images of vagina and cervix. The images were dense acetowhite and (or) thick mosaic, coarse punctate and atypical vessels. Lugol's staining was uniformly bright yellow or brown. Pathological biopsy of vaginal wall: 27 cases were metastatic carcinoma, 3 cases were vaginal intraepithelial neoplasia (VaIN) Ⅱ-Ⅲ. One case showed dense acetowhite epithelium and atypical vessels image in cervix and thin acetowhite epithelium in upper 1/3 vagina which disappeared in two minutes; the results of vaginal biopsy was chronic inflammation. (2) Vaginal invasion diagnosed by colposcopy: among 31 cases, 14 of them without invasion of uterine side, vaginal invasion was judged as followed by colposcopy, being consistent with biopsy: 1 case of chronic vaginitis, 2 cases VaINⅡ, 1 case VaINⅢ, 6 cases upper 1/3 vagina invasion, 4 cases lower 1/3 vagina invasion. Among 10 cases with invasion of uterine side, vaginal invasion were identified by colposcopy, being consistent with biopsy: 4 cases upper 1/3 vagina invasion and 6 cases upper 1/2 vagina invasion. Five cases who had clinical diagnosis of vaginal cancer were diagnosed as cervical cancer with vaginal invasion by colposcopy, being consistent with biopsy. Two cases with no obvious lesions of cervix and vagina were diagnosed as cervical cancer with vaginal invasion by colposcopy, being consistent with cervical and vaginal biopsy: 1 case with stage Ⅳ (transfer to the left supraclavicular lymph node) and 1 case with stage Ⅱ a1. Conclusions: Colposcopy and multi-point biopsy have complementary diagnostic value for the cervical cancer cases that the invasion and scope of vagina are difficult to be determined by physical examination and (or) imaging examination. Thus the range of vaginal resection for patients underwent operation and the lower boundary of pelvic radiation field for those underwent radiotherapy could be fixed, so as to make the treatment much more individualized and humanized; the indications need further discussion.

MiR-216a-3p suppresses the proliferation and invasion of cervical cancer through downregulation of ACTL6A-mediated YAP signaling.

The tumor-suppressive role of microRNA-216a-3p (miR-216a-3p) has been evidenced in multiple tumors. Yet, the relevance of miR-216a-3p in cervical cancer remains undermined. The current study was designed to determine the expression and potential function of miR-216a-3p in cervical cancer. Expression of miR-216a-3p was markedly decreased in cervical cancer and functional assays revealed an inhibitory effect of miR-216a-3p on the proliferation, colony formation, and invasion of cervical cancer. Actin-like 6A (ACTL6A) was identified as a target gene of miR-216a-3p. Elevated ACTL6A expression was detected in cervical cancer, and ACTL6A inhibition exhibited a tumor-suppressive effect. ACTL6A inhibition increased yes-associated protein (YAP) phosphorylation and downregulated YAP-mediated transcriptional activity. ACTL6A restoration or YAP reactivation partially abrogated the miR-216a-3p-mediated antitumor effect in cervical cancer cells. Taken together, these data demonstrate that miR-216a-3p acts as a potential tumor-suppressive miRNA in cervical cancer, which exerts its function through inhibition of YAP signaling via targeting ACTL6A.

FENDRR suppresses cervical cancer proliferation and invasion by targeting miR-15a/b-5p and regulating TUBA1A expression

BackgroundPrevious literature has revealed long non-coding RNAs (lncRNAs) are crucial regulators for cell functions and gene expression. LncRNA fetal-lethal non-coding developmental regulatory RNA (FENDRR) was reported as a biological suppressor in several types of human cancers, yet relevant mechanisms and biological effects of FENDRR with regards to cervical cancer (CC) are not explored until now.MethodsIn this study, quantitative real-time polymerase chain reaction (qRT-PCR) analysis detected gene expression in tissues and cells. Gain- or loss-of-function experiments revealed the biological effects of FENDRR and miR-15a/b-5p on CC cell functions. Bioinformatics tools were used to predict the relevant genes. Mechanism experiments including RNA immunoprecipitation (RIP) assay, pull down assay and luciferase reporter assay depicted the binding situation and coexistence of indicated genes.ResultsFENDRR was downregulated in CC tissues and cells, which suppressed CC progression. MiR-15a-5p and miR-15b-5p shared binding sites with FENDRR and had interaction with FENDRR. Tubulin alpha1A (TUBA1A) was downregulated in CC tissues and positively modulated by FENDRR. TUBA1A was the target of miR-15a/b-5p. TUBA1A silencing rescued the effect of FENDRR overexpression on CC cell growth and migration.ConclusionFENDRR inhibits CC progression through upregulating TUBA1A in a miR-15a/b-5p-dependent manner.

Circular RNA circNRIP1 promotes migration and invasion in cervical cancer by sponging miR-629-3p and regulating the PTP4A1/ERK1/2 pathway

Emerging evidence indicates that circRNAs play essential roles in tumorigenesis and development. However, the role of circRNAs in cervical cancer (CC) remains unclear. CircRNA microarrays performed on the immortal cervical cell line H8 and the cervical cancer cell line SiHa were used to identify a circRNA, termed circNRIP1 (hsa_circ_0004771), which was upregulated in SiHa. QRT-PCR confirmed that circNRIP1 was upregulated in CC tissues, where its expression was correlated with lymphovascular space invasion. Besides, both in vitro and in vivo experiments demonstrated that circNRIP1 promotes cell proliferation, migration, and invasion. Additionally, we found that miR-629-3p induced tumor suppression by regulating PTP4A1 and the ERK1/2 pathway. Finally, we confirmed that circNRIP1 exerts its effect, at least partially, by sponging miR-629-3p and thereby regulating the PTP4A1/ERK1/2 pathway. Therefore, circNRIP1 may be useful as a potential prognostic biomarker and therapeutic target in CC patients.

Life-threatening arterioureteral fistula treatment by endovascular complete anatomic iliac artery bifurcation reconstruction.

We present an endovascular approach for anatomic reconstruction of the iliac bifurcation in life-threatening arterioureteral fistula without sacrificing the pelvic arterial vascular supply. Five consecutive patients suffering from acute onset of significant gross hematuria caused by iliac-ureteral fistula resulting from previous oncologic surgery and radiation therapy were treated by transfemoral stent graft implantation in a double-barrel technique. Iliac-ureteral pseudoaneurysm coverage succeeded in an iliac neobifurcation with preservation of pelvic perfusion. Follow-up ranging from 9 to 37 months confirmed cessation of hematuria. One patient experienced stent graft thrombosis of the external iliac artery as a result of large cervical cancer invasion treated by crossover bypass. In all other patients, stent grafts were patent.

Long non-coding RNA MIAT promotes cervical cancer proliferation and migration.

Cervical cancer is one of the most common cancers in the world while its pathological mechanisms are not well-elucidated. Long non-coding RNA (lncRNA) has been implicated in cancer development. The dysregulation of lncRNA myocardial infarction-associated transcript (MIAT) has been reported in several cancers while its role in cervical cancer is not described yet. In this study, the role of MIAT in cervical cancer was explored. We evaluated the expression of MIAT in cervical cancer tissues and cell lines. Furthermore, we explored the effects of MIAT on proliferation and invasion of cervical cancer using cell model and animal transplantation model. We also evaluated the effects of MIAT on activation of PI3K/Akt/mTOR signalling pathway. Our results show that MIAT was up-regulated in cervical cancer tissues and cell lines. Knocking down MIAT resulted in decreased cell proliferation, migration and invasion of cervical cancer cells and suppression of tumour growth in mice. Mechanically, knocking down MIAT suppressed the activation of PI3K/Akt signalling pathway. In conclusion, MIAT promotes cell proliferation and invasion in cervical cancer.

Analysis of factors related to perineural invasion in cervical cancer and its relationship with prognosis

Objective To investigate the relationship between perineural invasion (PNI) and the clinicopathological features of cervical cancer, and to explore its influence on the prognosis of cervical cancer patients. Methods Retrospective analysis the clinical data of 76 patients with early cervical cancer who received radical hysterectomy+ pelvic lymphadenectomy±paraaortic lymphadenectomy from November 2015 to December 2019 in Xuanwu Hospital. The clinicopathological characteristics of the postoperative pathological results of cervical cancer patients were analyzed to explore the related factors of PNI and its influence on prognosis. Results Single factor analysis suggested that the incidence of PNI was related to tumor diameter, depth of stroma invasion, lymph-vascular space invasion, lymph node metastasis and clinical stage (P 0.05). Conclusions PNI is related to the depth of interstitial infiltration. PNI has no significant effect on the short-term recurrence rate and short-term survival rate of cervical cancer patients. Key words: Uterine cervical neoplasms; Perineural invasion; Prognosis; Factor analysis, statistical

Preoperative prediction of parametrial invasion in early-stage cervical cancer with MRI-based radiomics nomogram.

To develop and identify a MRI-based radiomics nomogram for the preoperative prediction of parametrial invasion (PMI) in patients with early-stage cervical cancer (ECC). All 137 patients with ECC (FIGO stages IB-IIA) underwent T2WI and DWI scans before radical hysterectomy surgery. The radiomics signatures were calculated with the radiomics features which were extracted from T2WI and DWI and selected by the least absolute shrinkage and selection operation regression. The support vector machine (SVM) models were built using radiomics signatures derived from T2WI and joint T2WI and DWI respectively to evaluate the performance of radiomics signatures for distinguishing patients with PMI. A radiomics nomogram was drawn based on the radiomics signatures with a better performance, patient's age, and pathological grade; its discrimination and calibration performances were estimated. For T2WI and joint T2WI and DWI, the radiomics signatures yielded an AUC of 0.797 (95% CI, 0.682-0.911) vs 0.946 (95% CI, 0.899-0.994), and 0.780 (95% CI, 0.641-0.920) vs 0.921 (95% CI, 0.832-1) respectively in the primary and validation cohorts. The radiomics nomogram, integrating the radiomics signatures from joint T2WI and DWI, patient's age, and pathological grade, showed excellent discrimination, with C-index values of 0.969 (95% CI, 0.933-1) and 0.941 (95% CI, 0.868-1) in the primary and validation cohorts, respectively. The calibration curve showed a good agreement. The radiomics nomogram performed well for the preoperative prediction of PMI in patients with ECC and may be used as a supplementary tool to provide individualized treatment plans for patients with ECC. • No previously reported study that has utilized radiomics nomogram to preoperatively predict PMI for patients with ECC. • Radiomics model involves radiomics features extracted from joint T2WI and DWI which characterize the heterogeneity between tumors in patients with ECC. • Radiomics nomogram can assist clinicians with individualized treatment decision-making for patients with ECC.

LINC01410 Knockdown Suppresses Cervical Cancer Growth and Invasion via Targeting miR-2467-3p/VOPP1 Axis.

BackgroundLong noncoding RNAs have essential roles in human diseases, including cancer. Our work aims to assess the function and mechanisms of LINC01410 in cervical cancer (CC) development.MethodsExpression analyses were performed using qRT-PCR. Proliferation was determined through CCK8 and colony formation assays. Cell migration and invasion were determined by Transwell assay. The interactions among LINC01410, miR-2467-3p and VOPP1 were analyzed via luciferase reporter assay.ResultsLINC01410 was upregulated in CC tissues and cell lines. LINC01410 upregulation correlated with poor prognosis. LINC01410 silencing suppressed proliferation, migration and invasion of CC cells. LINC01410 was the sponge for miR-2467. And LINC01410 promoted VOPP1 expression through inhibiting miR-2467.ConclusionOur findings demonstrated that LINC01410 contributed to CC progression through regulating miR-2467/VOPP1 axis and suggested that LINC01410/miR-2467/VOPP1 cascade may be a potential therapeutic target.

Schwann Cell-Derived CCL2 Promotes the Perineural Invasion of Cervical Cancer.

Perineural invasion (PNI) has guiding significances for nerve preservation in cervical cancer, but there is no definite marker indicating PNI. Two cervical cancer cell lines (HeLa and ME-180) showed significant abilities to migrate along neurites in vitro and in vivo. Morphological observation revealed that Schwann cells (SC) arrived at the sites of cervical cancer cells before the onset of cancer metastasis. We used high-throughput antibody array to screen the signals mediating the interaction of nerve cells and cancer cells and found the high expression of CCL2 in dorsal root ganglion (DRG). Meanwhile, serum CCL2 showed a notable raise especially in cervical adenocarcinoma. SC-derived CCL2 bound to its receptor CCR2 and promoted the proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT) of cervical cancer cells. In turn, cancer cell-derived signals triggered the expression of metalloproteinases (MMPs) including MMP2, MMP9, and MMP12 in SCs, promoting SCs to dissolve matrix. These data demonstrated that the cancer-nerve crosstalk formed a tumor microenvironment (TME) that facilitated to PNI. We identified the CCL2/CCR2 axis as a potential marker to predict the PNI and affect the nerve preservation for cervical cancer.

LINC00319 promotes migration, invasion and epithelial-mesenchymal transition process in cervical cancer by regulating miR-3127-5p/RPP25 axis

Cervical cancer is among the most prevalent malignancies for women. An increasing number of evidences have been proved that long non-coding RNAs (lncRNAs) play significant role in the initiation and progression of cervical cancer. However, the function of long intergenic non-protein coding RNA 319 (LINC00319) in cervical cancer still remains vague. In this study, our purpose was to investigate the effects of LINC00319 on cell migration, invasion and epithelial-mesenchymal transition (EMT) process in cervical cancer. It confirmed that LINC00319 was highly expressed in tissues and cell lines in cervical cancer. Further, overexpression of LINC00319 accelerates cell migration, invasion and EMT in cervical cancer. Moreover, LINC00319 could bind with miR-3127-5p and negatively regulated its expression. Besides, RPP25 was targeted by miR-3127-5p, and its expression was negatively/positively regulated by miR-3127-5p/LINC00319. Additionally, miR-3127-5p mimics or RPP25 insufficiency could offset the encouraging effects of LINC00319 overexpression on migration, invasion and EMT process in cervical cancer. Generally speaking, LINC00319 promotes migration, invasion and EMT process in cervical cancer by regulating miR-3127-5p/RPP25 axis, which may be conductive to cervical cancer treatment.

MRI Based Radiomics Approach With Deep Learning for Prediction of Vessel Invasion in Early-Stage Cervical Cancer.

This article aims to build deep learning-based radiomic methods in differentiating vessel invasion from non-vessel invasion in cervical cancer with multi-parametric MRI data. A set of 1,070 dynamic T1 contrast-enhanced (DCE-T1) and 986 T2 weighted imaging (T2WI) MRI images from 167 early-stage cervical cancer patients (January 2014 - August 2018) were used to train and validate deep learning models. Predictive performances were evaluated using receiver operating characteristic (ROC) curve and confusion matrix analysis, with the DCE-T1 showing more discriminative results than T2WI MRI. By adopting an attention ensemble learning strategy that integrates both MRI sequences, the highest average area was obtained under the ROC curve (AUC) of 0.911 (Sensitivity = 0.881 and Specificity = 0.752). The superior performances in this article, when compared to existing radiomic methods, indicate that a wealth of deep learning-based radiomics could be developed to aid radiologists in preoperatively predicting vessel invasion in cervical cancer patients.

Siva 1 Inhibits Cervical Cancer Progression and Its Clinical Prognosis Significance.

BackgroundCervical cancer is the second most common female malignancies. But the exact etiology of cervical cancer is still under investigation. Recent observations revealed that the loss expression of Siva 1 was related to several different types of tumors. It could play an indispensable role in both exogenous and endogenous apoptotic signaling pathways. Nevertheless, the relationship between Siva 1 expression and cervical cancer progression has not yet been fully clarified. This study aimed to explore the functional role of Siva1 in cervical cancer.Materials and MethodsIn this present experiment, expression of Siva 1 was detected in 87 cervical cancer, 34 CIN and 20 normal samples by immunohistochemistry. The correlation of Siva 1 expression and overall survival times (OS) was analyzed by Kaplan–Meier analysis. We up-regulated the expression of Siva 1 by plasmid pCMV3-Siva 1 in C33A cells. CCK8, flow cytometry, wound-healing, and transwell assays were performed to examine the influences of Siva 1 expression on cell proliferation, apoptosis, migration and invasion.ResultsThe expression of Siva 1 was decreased in cervical cancer tissues compared with CIN and normal tissues. In addition, the Siva 1 immunoreactivity was significantly associated with tumor differentiation. Patients with Siva 1 negative staining exhibited a significantly decreased overall survival. Then, we established stable Siva 1 ectopic expression cells, and we found that elevated expression of Siva 1 promoted apoptosis, inhibited proliferation, and suppressed migration and invasion of cervical cancer cells.ConclusionThe present study revealed a crucial role of Siva 1 in tumor progression and it may be a valuable prognostic indicator of cervical cancer.

Long non-coding RNA MALAT1 promotes cell proliferation, migration and invasion in cervical cancer by targeting miR-625-5p and AKT2.

Long non-coding RNA MALAT1 promotes cell proliferation, migration and invasion in cervical cancer by targeting miR-625-5p and AKT2.

Decreased Expression of Retinoblastoma Protein-Interacting Zinc-Finger Gene 1 Is Correlated With Poor Survival and Aggressiveness of Cervical Cancer Patients.

Background: Retinoblastoma protein-interacting zinc finger gene 1 (RIZ1) is a tumor suppressor deregulated in several human cancers. We aim to (1) explore RIZ1 expression in FIGO stages I–II cervical cancer tissues and its association with the clinical outcome of cervical cancer patients, (2) the role of RIZ1 in proliferation, apoptosis, migration, and invasion in cervical cancer cells.Methods: The expression of RIZ1 in 268 cervical cancer tissues and 30 paired adjacent non-tumor tissues were assessed by immunohistochemistry. We also examined RIZ1 at mRNA and protein level in 20 paired fresh frozen cervical cancer tissues and the adjacent non-tumor tissue using real-time PCR and western blot. We then examined proliferation, apoptosis, migration, and invasion in two human cervical cancer cells, HeLa and SiHa, with overexpression of RIZ1.Results: RIZ1 expression generally decreased in cervical cancer tissues. Decreased RIZ1 expression was significantly correlated with advanced FIGO stage (P = 0.005), deep stromal invasion (P = 0.001), lymphovascular space involvement (P = 0.041), pelvic lymph node metastasis (P = 0.005), and postoperative recurrence (P = 0.002). Kaplan-Meier analysis demonstrated that patients with low RIZ1 expression had shorter overall survival (OS) and disease-free survival (DFS) than those with high RIZ1 expression. Multivariate analysis showed that RIZ1 was an independent prognostic factor for DFS (HR = 2.184, 95% CI 1.365–3.496, P = 0.001) and OS (HR = 1.899, 95% CI 1.112–3.241, P = 0.019). In vitro analysis demonstrated that overexpression of RIZ1 inhibited cell proliferation, migration, and invasion, but promoted apoptosis in HeLa and SiHa cells.Conclusion: Down-regulation of RIZ1 may contribute to tumor migration, invasiveness, and poor survival of cervical cancer patients. RIZ1 may be a prognostic biomarker for cervical cancer patients.

The Association of Parametrial Invasion with the Expression of Vascular Endothelial Growth Factor-C and Other Factors in Squamous Cell Cervical Carcinoma Stage IB and IIA

BACKGROUND: The presence of parametrial invasion in early stage squamous cell cervical cancer (SCCC) indeed indicates worse prognosis and need more adjuvant treatment. This study aimed to investigate the association between parametrial invasion and clinicohystopathology variables.METHODS: This retrospective study used specimens of squamous cell carcinoma stage IB-IIA. The inclusion criteria were cervical cancer stage IB-IIA and post radical hysterectomy with lymph node dissection and exclusion criteria was damaged and or insufficient histological preparations. The clinicohystopathology variables included age, tumour size and stage, differentiation and inflammation grade, lymphatic vascular and parametrial invasion, and lymph node metastasis. Histopathology staining, immunohistochemistry examination, and vascular endothelial growth factor-C (VEGF-C) expression were evaluated according to the standard procedure. The independent-T, Chi square, and Fisher’s exact test were applied to evaluate the association. The significance was set at p&lt;0.05.RESULTS: Seventy-five cases were eligible. Parametrial invasion was found in 15 cases (20%). Three variables demonstrated a significant association with parametrial invasion, tumor size &gt;4 cm (OR 4.32, 95% CI 1.29-14.38, p=0.01), lymphatic node metastasis (OR 3.90, 95% CI 1.17-13.03, p=0.02), and VEGF-C (OR 0.75, 95% CI 0.65- 0.87, p=0.03).CONCLUSION: Tumor size of &gt;4 cm and lymph node metastasis (LNM) had a higher risk of parametrial invasion in SCCC stage IB-IIA.KEYWORDS: cervical carcinoma, parametrial invasion, vascular invasion, peritumoral stroma, VEGF-C expression