Annexin A2 combined with TTK accelerates esophageal cancer progression via the Akt/mTOR signaling pathway.

Annexin A2 (ANXA2) is a widely reported oncogene. However, the mechanism of ANXA2 in esophageal cancer is not fully understood. In this study, we provided evidence that ANXA2 promotes the progression of esophageal squamous cell carcinoma (ESCC) through the downstream target threonine tyrosine kinase (TTK). These results are consistent with the up-regulation of ANXA2 and TTK in ESCC. In vitro experiments by knockdown and overexpression of ANXA2 revealed that ANXA2 promotes the progression of ESCC by enhancing cancer cell proliferation, migration, and invasion. Subsequently, animal models also confirmed the role of ANXA2 in promoting the proliferation and metastasis of ESCC. Mechanistically, the ANXA2/TTK complex activates the Akt/mTOR signaling pathway and accelerates epithelial-mesenchymal transition (EMT), thereby promoting the invasion and metastasis of ESCC. Furthermore, we identified that TTK overexpression can reverse the inhibition of ESCC invasion after ANXA2 knockdown. Overall, these data indicate that the combination of ANXA2 and TTK regulates the activation of the Akt/mTOR pathway and accelerates the progression of ESCC. Therefore, the ANXA2/TTK/Akt/mTOR axis is a potential therapeutic target for ESCC.

Single Multifunctional Nanocabinets-Based Target-Activated Feedback for Simultaneously Precise Monitoring and Therapy.

Stimulus-responsive mode is highly desirable for improving the precise monitoring and physiological efficacy of endogenous biomarkers (EB). However, its integrated application for visual detection and therapy is limited by inappropriate use of responsive triggers and poor delivery of EB signal-transducing agents, which remain challenging in simultaneous monitoring and noninvasive therapy of EB and EB-mediated pathological events. Target microRNA (miRNA) as controllable reaction triggers and DNAzyme as signal-transducing agent are proposed to develop target-stimulated multifunctional nanocabinets (MFNCs) for the visual tracking of both miRNA and miRNA-mediated anticancer events. The MFNCs, equipped with a target-discriminating sequence-incorporated DNAzyme motif, can specifically release therapeutic molecules through target-triggered conformational switches, accompanied by transduction signal output. Target detection and molecule release performance are recorded in parallel via reverse dual-signal feedback at the single-molecule level. In addition, the intrinsic thermal-replenishing of the MFNCs leads to tumor ablation without invasive exogenous aids. The system achieves visual target quantification, anticancer molecule real-time tracking, and tumor suppression in vivo and in vitro. This work proposes a new paradigm for precise visual exploration of EB or EB-mediated bio-events and provides a demonstration of efficacious all-in-one detection and therapy based on the target-triggered multifunctional nanosystem.

Engineering of Multivalent Membrane-Anchored DNA Frameworks for Precise Profiling of Variable Membrane Permeability During Reversible Electroporation.

Electroporation techniques have emerged as attractive tools for intracellular delivery, rendering promising prospects towards clinical therapies. Transient disruption of membrane permeability is the critical process for efficient electroporation-based cargo delivery. However, smart nanotools for precise characterization of transient membrane changes induced by strong electric pulses are extremely limited. Herein, multivalent membrane-anchored fluorescent nanoprobes (MMFNPs) that take advantages of flexible functionalization and spatial arrangement of DNA frameworks are developed for in situ evaluation of electric field-induced membrane permeability during reversible electroporation . Single-molecule fluorescence imaging techniques are adopted to precisely  verify the excellent analytical performance of the engineered MMFNPs. Benefited from tight membrane anchoring and sensitive adenosine triphosphate (ATP) profiling, varying degrees of membrane disturbances are visually exhibited under different intensities of the microsecond pulse electric field (µsPEF). Significantly, the dynamic process of membrane repair during reversible electroporation is well demonstrated via ATP fluctuations monitored by the designed MMFNPs. Furthermore, molecular dynamics (MD) simulations are performed for accurate verification of electroporation-driven dynamic cargo entry via membrane nanopores. This work provides an avenue for effectively capturing transient fluctuations of membrane permeability under external stimuli, offering valuable guidance for developing efficient and safe electroporation-driven delivery strategies for clinical diagnosis and therapeutics.

Nanoarray Enabled Size-Dependent Isolation and Proteomics Profiling of Small Extracellular Vesicle Subpopulations toward Accurate Cancer Diagnosis and Prognosis.

Small extracellular vesicles (sEVs) have emerged as noninvasive biomarkers in liquid biopsy due to their significant function in pathology and physiology. However, the phenotypic heterogeneity of sEVs presents a significant challenge to their study and has significant implications for their applications in liquid biopsies. In this study, anodic aluminum oxide films with different pore sizes (AAO nanoarray) were introduced to enable size-based isolation and downstream proteomics profiling of sEV subpopulations. The adjustable pore size and abundant Al3+ on the framework of AAOs allowed size-dependent isolation of sEV subpopulations through nanoconfined effects and Lewis acid-base interaction between AAOs and sEVs. Benefiting from the strong concerted effect, the simple AAO nanoarray enabled specific isolation of three sEV subpopulations, termed "50", "90", and "150 nm" groups, from 10 µL of complex biological samples within 10 min with high capture efficiencies and purities. Moreover, the nanopores of AAOs also acted as nanoreactors for comprehensive proteomic profiling of the captured sEV subpopulations to reveal their heterogeneity. The AAO nanoarray was first investigated on sEVs from a cell culture medium, where sEV subpopulations could be clearly distinguished, and three traditional sEV-specific proteins (CD81, CD9, and FLOT1) could be identified by proteomic analysis. A total of 3946, 3951, and 3940 proteins were identified from 50, 90, and 150 nm sEV subpopulations, respectively, which is almost twice the number compared to those obtained from the conventional approach. The concept was further applied to complex real-case sample analysis from prostate cancer patients. Machine learning and gene ontology (GO) information analysis of the identified proteins indicate that different-sized sEV subpopulations contain unique protein cargos and have distinct cellular components and molecular functions. Further receiver operating characteristic curve (ROC) analysis of the top five differential proteins from the three sEV subpopulations demonstrated the high accuracy of the proposed approach toward prostate cancer diagnosis (AUC > 0.99). More importantly, several proteins involved in focal adhesion and antigen processing and presentation pathways were found to be upregulated in prostate cancer patients, which may serve as potential biomarkers of prostate cancer. These results suggest that the sEV subpopulation-based AAO nanoarray is of great value in facilitating the early diagnosis and prognosis of cancer and opens a new avenue for sEVs in liquid biopsy.

CDK2-activated TRIM32 phosphorylation and nuclear translocation promotes radioresistance in triple-negative breast cancer.

INTRODUCTION: Despite radiotherapy being one of the major treatments for triple-negative breast cancer (TNBC), new molecular targets for its treatment are still required due to radioresistance. CDK2 plays a critical role in TNBC. However, the mechanism by which CDK2 promotes TNBC radioresistance remains to be clearly elucidated. OBJECTIVES: We aimed to elucidate the relationship between CDK2 and TRIM32 and the regulation mechanism in TNBC. METHODS: We performed immunohistochemical staining to detect nuclear TRIM32, CDK2 and STAT3 on TNBC tissues. Western blot assays and PCR were used to detect the protein and mRNA level changes. CRISPR/Cas9 used to knock out CDK2. shRNA-knockdown and transfection assays also used to knock out target genes. GST pull-down analysis, immunoprecipitation (IP) assay and in vitro isomerization analysis also used. Tumorigenesis studies also used to verify the results in vitro. RESULTS: Herein, tripartite motif-containing protein 32 (TRIM32) is revealed as a substrate of CDK2. Radiotherapy promotes the binding of CDK2 and TRIM32, thus leading to increased CDK2-dependent phosphorylation of TRIM32 at serines 328 and 339. This causes the recruitment of PIN1, involved in cis-trans isomerization of TRIM32, resulting in importin α3 binding to TRIM32 and contributing to its nuclear translocation. Nuclear TRIM32 inhibits TC45-dephosphorylated STAT3, Leading to increased transcription of STAT3 and radioresistance in TNBC. These results were validated by clinical prognosis confirmed by the correlative expressions of the critical components of the CDK2/TRIM32/STAT3 signaling pathway. CONCLUSIONS: Our findings demonstrate that regulating the CDK2/TRIM32/STAT3 pathway is a promising strategy for reducing radioresistance in TNBC.

SRPX2 promotes cancer cell proliferation and migration of papillary thyroid cancer.

Thyroid cancer is the endocrine tumor with the highest incidence at present. It originates from the thyroid follicular epithelium or follicular paraepithelial cells. There is an increasing incidence of thyroid cancer all over the world. We found that SRPX2 expression level was higher in papillary thyroid tumors than in normal thyroid tissues, and SRPX2 expression was closely related to tumor grade and clinical prognosis. Previous reports showed that SRPX2 could function by activating PI3K/AKT signaling pathway. In addition, in vitro experiments showed that SRPX2 promoted the proliferation and migration of papillary thyroid cancer (PTC). In conclusion, SRPX2 could promote the malignant development of PTC. This may be a potential treatment target for PTC.

STNM1 in human cancers: role, function and potential therapy sensitizer.

STMN1 belongs to the stathmin gene family, it encodes a cytoplasmic phosphorylated protein, stathmin1, which is commonly observed in vertebrate cells. STMN1 is a structural microtubule-associated protein (MAP) that binds to microtubule protein dimers rather than microtubules, with each STMN1 binding two microtubule protein dimers and preventing their aggregation, leading to microtubule instability. STMN1 expression is elevated in a number of malignancies, and inhibition of its expression can interfere with tumor cell division. Its expression can change the division of tumor cells, thereby arresting cell growth in the G2/M phase. Moreover, STMN1 expression affects tumor cell sensitivity to anti-microtubule drug analogs, including vincristine and paclitaxel. The research on MAPs is limited, and new insights on the mechanism of STMN1 in different cancers are emerging. The effective application of STMN1 in cancer prognosis and treatment requires further understanding of this protein. Here, we summarize the general characteristics of STMN1 and outline how STMN1 plays a role in cancer development, targeting multiple signaling networks and acting as a downstream target for multiple microRNAs, circRNAs, and lincRNAs. We also summarize recent findings on the function role of STMN1 in tumor resistance and as a therapeutic target for cancer.

Post-translational modifications of histones: Mechanisms, biological functions, and therapeutic targets.

Histones are DNA-binding basic proteins found in chromosomes. After the histone translation, its amino tail undergoes various modifications, such as methylation, acetylation, phosphorylation, ubiquitination, malonylation, propionylation, butyrylation, crotonylation, and lactylation, which together constitute the "histone code." The relationship between their combination and biological function can be used as an important epigenetic marker. Methylation and demethylation of the same histone residue, acetylation and deacetylation, phosphorylation and dephosphorylation, and even methylation and acetylation between different histone residues cooperate or antagonize with each other, forming a complex network. Histone-modifying enzymes, which cause numerous histone codes, have become a hot topic in the research on cancer therapeutic targets. Therefore, a thorough understanding of the role of histone post-translational modifications (PTMs) in cell life activities is very important for preventing and treating human diseases. In this review, several most thoroughly studied and newly discovered histone PTMs are introduced. Furthermore, we focus on the histone-modifying enzymes with carcinogenic potential, their abnormal modification sites in various tumors, and multiple essential molecular regulation mechanism. Finally, we summarize the missing areas of the current research and point out the direction of future research. We hope to provide a comprehensive understanding and promote further research in this field.

The roles, molecular interactions, and therapeutic value of CDK16 in human cancers.

Cyclin-dependent kinase 16 (CDK16) is an orphan "cyclin-dependent kinase" (CDK) involved in the cell cycle, vesicle trafficking, spindle orientation, skeletal myogenesis, neurite outgrowth, secretory cargo transport, spermatogenesis, glucose transportation, cell apoptosis, cell growth and proliferation, metastasis, and autophagy. Human CDK16 is located on chromosome Xp11.3 and is related to X-linked congenital diseases. CDK16 is commonly expressed in mammalian tissues and may act as an oncoprotein. It is a PCTAIRE kinase in which Cyclin Y or its homologue, Cyclin Y-like 1, regulates activity by binding to the N- and C- terminal regions of CDK16. CDK16 plays a vital role in various cancers, including lung cancer, prostate cancer, breast cancer, malignant melanoma, and hepatocellular carcinoma. CDK16 is a promising biomarker for cancer diagnosis and prognosis. In this review, we summarized and discussed the roles and mechanisms of CDK16 in human cancers.

Severe lymphopenia as a prognostic factor in rectal cancer patients receiving adjuvant chemoradiotherapy: a retrospective study.

The relationship between total lymphocyte counts (TLCs) and survival is not well documented in rectal cancer. This study aimed to investigate the association between TLCs and disease-free survival (DFS) and identify factors associated with lymphopenia in locally advanced rectal cancer patients receiving chemoradiotherapy. Thirty-six patients with locally advanced rectal cancer were retrospectively analyzed. TLCs were evaluated before surgery (pre-S), before radiotherapy (pre-RT), and during concurrent chemoradiotherapy (CCRT). The relationship between TLCs and DFS was analyzed by univariate and multivariate analysis. Potential clinical factors associated with lymphopenia were also evaluated. Median TLC declined significantly during radiotherapy. Severe lymphopenia during CCRT was significantly associated with poorer DFS on Kaplan-Meier analysis (p = 0.01), univariate regression analysis (p = 0.036), and multivariate regression analysis (p = 0.038). Pre-S TLCs (p = 0.009) and pre-RT TLCs (p = 0.042) were significantly associated with severe lymphopenia on univariate regression analysis; however, only pre-S TLCs (p = 0.026) were significantly associated with severe lymphopenia on multivariate regression analysis. Severe lymphopenia was a predictor of poorer DFS in patients with locally advanced rectal cancer receiving adjuvant chemoradiotherapy. Pre-S TLCs were predictors of severe lymphopenia. Further study is warranted to reduce the rate of severe lymphopenia.

[Effect of transcutaneous electrical acupoint stimulation combined with auricular acupressure on sexual hormone level and gonadal development in girls with precocious puberty].

OBJECTIVE: To explore the effect of transcutaneous electrical acupoint stimulation (TEAS) combined with auricular acupressure on serum sexual hormone level, and the ovarian, follicular and uterine development in the girls with precocious puberty. METHODS: Sixty girls with precocious puberty were randomly divided into a control group (30 cases, 2 cases dropped off) and a treatment group (30 cases, 3 cases dropped off). In both the control group and the treatment group, the healthy life-style intervention was provided for 12 weeks. Besides, in the treatment group, TEAS was delivered for 20 minutes each time, twice a week; and bilateral auricular acupressure was combined. The duration of treatment was 12 weeks. The levels of serum luteinizing hormone (LH), follicle stimulating hormone (FSH) and estradiol (E2), as well as ovarian volume, maximum follicular diameter and uterine volume before and after treatment were detected, and the safety was evaluated separately. RESULTS: Compared with before treatment, the contents of serum LH and FSH were increased (P<0.05), and the ovarian volume and the maximum follicle diameter were increased (P<0.05) in the control group after treatment; the contents of serum FSH and E2 were decresed (P<0.05), and the maximum follicular diameter was reduced significantly (P<0.05) in the treatment group after treatment. Compared with the control group, the contents of serum LH, FSH and E2 were decreased (P<0.05), while the ovarian volume and the maximum follicle diameter were decreased (P<0.05) in the treatment group after treatment. CONCLUSION: TEAS combined with auricular acupressure can effectively decrease the level of sex hormone, improve the ovarian and uterine development and retard the gonadal development. Such combined therapy is of high safety and conductive to regulating the development for the girls with precocious puberty.

A 5-year survival status prognosis of nonmetastatic cervical cancer patients through machine learning algorithms.

BACKGROUND: Prediction models with high accuracy rates for nonmetastatic cervical cancer (CC) patients are limited. This study aimed to construct and compare predictive models on the basis of machine learning (ML) algorithms for predicting the 5-year survival status of CC patients through using the Surveillance, Epidemiology, and End Results public database of the National Cancer Institute. METHODS: The data registered from 2004 to 2016 were extracted and randomly divided into training and validation cohorts (8:2). The least absolute shrinkage and selection operator (LASSO) regression was employed to identify significant factors. Then, four predictive models were constructed, including logistic regression (LR), random forest (RF), support vector machine (SVM), and extreme gradient boosting (XGBoost). The predictive models were evaluated and compared using Receiver-operating characteristics with areas under the curves (AUCs) and decision curve analysis (DCA), respectively. RESULTS: A total of 13,802 patients were involved and classified into training (N = 11,041) and validation (N = 2761) cohorts. By using the LASSO regression method, seven factors were identified. In the training cohort, the XGBoost model showed the best performance (AUC = 0.8400) compared to the other three models (all p < 0.05 by Delong's test). In the validation cohort, the XGBoost model also demonstrated a superior prediction ability (AUC = 0.8365) than LR and SVM models (both p < 0.05 by Delong's test), although the difference was not statistically significant between the XGBoost and the RF models (p = 0.4251 by Delong's test). Based on the DCA results, the XGBoost model was also superior, and feature importance analysis indicated that the tumor stage was the most important variable among the seven factors. CONCLUSIONS: The XGBoost model proved to be an effective algorithm with better prediction abilities. This model is proposed to support better decision-making for nonmetastatic CC patients in the future.

Breast metastasis of signet ring cell carcinoma from the colon: a case report.

BACKGROUND: Colon cancer is one of the most common diagnosed malignancies. Despite the use of surgery, chemotherapy, radiotherapy, targeted therapy, immunotherapy, and other comprehensive treatments, distant metastasis is still one of the main causes for dying of colon cancer. The common metastatic site of colon cancer is the liver, lung, and bone. In this article, we report a rare case of breast metastasis of signet ring cell carcinoma from the colon. CASE PRESENTATION: A 44-year-old woman was diagnosed with colon cancer and received a radical surgery of colon cancer in 2019. Combined with postoperative pathological and computed tomography (CT) images, a diagnosis of cT3N2M0 mucinous adenocarcinoma of colon (according to AJCC cancer staging manual, Version 8) was established. Adjuvant chemotherapy (XELOX: oxaliplatin 130 mg/m2 on day 1 plus capecitabine 1000 mg/m2 twice daily on days 1 to 14 every 3 weeks for 18 weeks) was performed followed by surgical resection. Fourteen months later, the patient underwent mastectomy for breast mass, which was diagnosed pathologically as metastasis of signet ring cell carcinoma from the colon. XELOX chemotherapy regimen (oxaliplatin 130 mg/m2 on day 1 plus capecitabine 1000 mg/m2 twice daily on days 1 to 14 every 3 weeks for 24 weeks) combined with bevacizumab (7.5 mg/kg on day 1) was used after the mastectomy. The patient had stable disease according to her last examination (RECIST criteria). CONCLUSION: It is rare to find a report of a patient of colon cancer that metastasizes to breast. We hope to increase treatment experience for patients with this rare metastasis.

Long non-coding RNA PVT1: A promising chemotherapy and radiotherapy sensitizer.

The long non-coding RNA (lncRNA) PVT1 was first found to activate variant translocations in the plasmacytoma of mice. Human lncPVT1 is located on chromosome 8q24.21, at the same locus as the well-known MYC oncogene. LncPVT1 has been found to promote the progression of various malignancies. Chemoresistance and radioresistance seriously affect tumor treatment efficacy and are associated with the dysregulation of physiological processes in cancer cells, including apoptosis, autophagy, stemness (for cancer stem cells, CSC), hypoxia, epithelial-mesenchymal transition (EMT), and DNA damage repair. Previous studies have also implicated lncPVT1 in the regulation of these physiological mechanisms. In recent years, lncPVT1 was found to modulate chemoresistance and radioresistance in some cancers. In this review, we discuss the mechanisms of lncPVT1-mediated regulation of cellular chemoresistance and radioresistance. Due to its high expression in malignant tumors and sensitization effect in chemotherapy and radiotherapy, lncPVT1 is expected to become an effective antitumor target and chemotherapy and radiotherapy sensitizer, which requires further study.

Long non-coding RNA LINC00152 in cancer: Roles, mechanisms, and chemotherapy and radiotherapy resistance.

Long non-coding RNA LINC00152 (cytoskeleton regulator, or LINC00152) is an 828-bp lncRNA located on chromosome 2p11.2. LINC00152 was originally discovered during research on hepatocarcinogenesis and has since been regarded as a crucial oncogene that regulates gene expression in many cancer types. LINC00152 is aberrantly expressed in various cancers, including gastric, breast, ovarian, colorectal, hepatocellular, and lung cancer, and glioma. Several studies have indicated that LINC00152 is correlated with cell proliferation, apoptosis, migration, invasion, cell cycle, epithelial-mesenchymal transition (EMT), chemotherapy and radiotherapy resistance, and tumor growth and metastasis. High LINC00152 expression in most tumors is significantly associated with poor patient prognosis. Mechanistic analysis has demonstrated that LINC00152 can serve as a competing endogenous RNA (ceRNA) by sponging miRNA, regulating the abundance of the protein encoded by a particular gene, or modulating gene expression at the epigenetic level. LINC00152 can serve as a diagnostic or prognostic biomarker, as well as a therapeutic target for most cancer types. In the present review, we discuss the roles and mechanisms of LINC00152 in human cancer, focusing on its functions in chemotherapy and radiotherapy resistance.

Retraction Notice to: Comprehensive analysis of FKBP4/NR3C1/TMEM173 signaling pathway in triple-negative breast cancer cell and dendritic cell among tumor microenvironment.

[This retracts the article DOI: 10.1016/j.omto.2021.12.024.].

In situ ratiometric SERS imaging of intracellular protease activity for subtype discrimination of human breast cancer.

Accurate discrimination between different cells at the molecular level is of fundamental importance for disease diagnosis. Endogenous proteases are such molecular candidates for cancer cell subtype study. But in situ probing their activity in live cells remains challenging for surface-enhanced Raman scattering (SERS). Here, we present a sensitive ratio-type SERS nanoprobe for imaging of matrix metalloproteinase-2 (MMP-2) in different cancer cells subtypes. The nanoprobe contained three components: a plasmon-active gold nanoparticle as the SERS enhancing matrix, Raman dye rhodamine B (Rh B)-labelled substrate peptides as the specific MMP-2 recognizer, and 2-naphthalenethiol (2-NT) as the internal standard. MMP-2-responsive cleavage of peptides from the nanoprobe surface results in decrease or even disappearance of SERS emission of Rh B, which was ratioed over the emission of 2-NT for the quantification of MMP-2 activity. Both in-tube assay and in-cell imaging results show that the MMP-responsive nanoprobe can work and serve to differentiate the normal breast cells from the tumorous ones, to differentiate two breast cancer cell subtypes with a different degree of malignancy. We believe that this SERS nanoprobe could find a wide application in the fields of tumor biology and accurate disease diagnosis.

Comprehensive analysis of FKBP4/NR3C1/TMEM173 signaling pathway in triple-negative breast cancer cell and dendritic cell among tumor microenvironment.

TMEM173 is a pattern recognition receptor detecting cytoplasmic nucleic acids and transmits cGAS related signals that activate host innate immune responses. It has also been found to be involved in tumor immunity and tumorigenesis. In this study, we first identified that the FKBP4/NR3C1 axis was a novel negative regulator of TMEM173 in human breast cancer (BC) cells. The effect of FKBP4 appeared to be at the transcriptional level of TMEM173, because it could suppress the promoter activity of TMEM173, thereby affecting TMEM173 at mRNA and protein levels. Past studies, our bioinformatics analysis, and in vitro experiments further implied that FKBP4 regulated TMEM173 via regulating nuclear translocation of NR3C1. We then demonstrated that the FKBP4/NR3C1/TMEM173 signaling pathway could regulate autophagy and proliferation of BC cells as well as dendritic cell (DC) abundance through exosome release. Our study found an unprecedented strategy used by BC to escape from TMEM173 mediated tumor suppression. Identification of the FKBP4/NR3C1 axis as a novel TMEM173 regulator would provide insights for novel anti-tumor strategy against BC among tumor microenvironment.

Long-Term Survival Outcomes and Comparison of Different Treatment Modalities for Stage I-III Cervical Esophageal Carcinoma.

Purpose: To investigate the survival outcomes, prognostic factors and treatment modalities of stage I-III cervical esophageal carcinoma (CEC) patients using data from the Surveillance, Epidemiology, and End Results (SEER) database from the period 2004-2016. Methods: Patients with a histopathologic diagnosis of CEC were included. The primary endpoint was overall survival (OS). Univariate and multivariate analyses of OS were performed using Cox proportional hazards models, and OS was compared using the Kaplan-Meier method and log-rank test. Results: A total of 347 patients in the SEER database were enrolled. The median OS was 14.0 months, with a 5-year OS rate of 20.9%. The parameters that were found to significantly correlate with OS in the multivariate analysis were age at diagnosis [P < 0.001, hazard ratio (HR) = 1.832], sex [P < 0.001, HR= 1.867], histology [P = 0.001, HR = 0.366], surgery at the primary site [P = 0.021, HR = 0.553], radiotherapy (RT, P = 0.017, HR = 0.637) and chemotherapy (CT, P < 0.001, HR = 0.444). Comparison among the three treatment modalities demonstrated that a triple therapy regimen consisting of surgery, RT and CT was associated with a longer survival time than the other two treatment modalities before and after propensity score matching (PSM). However, triple therapy showed no significant survival benefit over double therapy (P = 0.496 before PSM and P = 0.184 after PSM). Conclusions: The survival of patients with CEC remains poor. Surgery, RT and CT were all strongly correlated with OS. We recommend a triple therapy regimen for select CEC patients based on the findings of the current study, although this recommendation should be further confirmed by prospective studies with large sample sizes.