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OBJECTIVES@#The high morbidity and mortality of colorectal cancer (CRC) have posed great threats to human health. Circular RNA (circRNA) and microRNA (miRNA), acting as competing endogenous RNAs (ceRNAs), have been found to play vital roles in carcinogenesis. This paper aims to construct a circRNA/miRNA/mRNA regulatory network so as to explore the molecular mechanism of CRC.@*METHODS@#The sequencing data of circRNA from CRC were obtained from Gene Expression Omnibus (GEO). The differential circRNA was screened and its structure was identified by Cancer-specific CircRNA Database (CSCD); the sequencing data of miRNA and messenger RNA (mRNAs) were downloaded from The Cancer Genome Atlas (TCGA) database and the differentially expressed genes were screened; the corresponding miRNA of differential circRNAs were predicted by CircInteractome database; DIANA, Miranda, PicTar, and TargetScan databases were used to predict the target genes of different miRNAs; the target genes from Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) were enriched by R language; String database combined with Cytoscape 3.7.2 software was used to construct protein-protein interaction (PPI) network and hub genes were screened; the expressions of mRNAs in the Top10 hub genes were verified in CRC. The network diagrams of circRNAs/miRNAs/mRNAs and circRNAs/miRNAs/Top10 hub mRNAs were constructed by Cytoscape3.7.2. Real-time PCR was used to examine the expression levels of hsa_circRNA_0065173, hsa-mir-450b, hsa-mir-582, adenylate cyclase 5 (ADCY5), muscarinic acetylcholine receptor M2 (CHRM2), cannabinoid receptor 1 (CNR1), and lysophosphatidic acid receptor 1 (LPAR1) in the CRC tissues and the adjacent normal tissues.@*RESULTS@#A total of 14 differential circRNAs were identified, and 8 were found in CSCD; 34 miRNAs targeted by circRNAs were obtained. The PPI network was constructed, and the Top10 hub genes were identified, which were CHRM2, melanin concentrating hormone receptor 2 (MCHR2), G-protein gamma 3 subunit (GNG3), neuropeptide Y receptor Y1 (NPY1R), CNR1, LPAR1, ADCY5, adenylate cyclase 2 (ADCY2), gamma 7 (GNG7) and chemokine 12 (CXCL12), respectively. The expressions of Top 10 hub genes were also verified, and the results showed that the Top 10 hub genes were down-regulated in CRC; the constructed network diagram showed that hsa_circRNA_0065173 may regulate ADCY5, CHRM2, and Hsa-mir-450b by modulating hsa-mir-450b and hsa-mir-582. CNR1 and LPAR1 genes might serve as potentially relevant targets for the treatment of CRC. Real-time PCR results showed that the expression levels of hsa_circRNA_0065173, ADCY5, CHRM2, CNR1 and LPAR1 in the CRC tissues were significantly reduced compared with the adjacent normal tissues (all P<0.05); the expression levels of hsa-mir-450b and hsa-miR-582 were significantly increased (both P<0.05).@*CONCLUSIONS@#In this study, a potential circRNAs/miRNAs/mRNAs network is successfully constructed, which provides a new insight for CRC development mechanism through ceRNA mediated by circRNAs.
Subject(s)
Humans , Colorectal Neoplasms/genetics , Computational Biology/methods , Gene Regulatory Networks , MicroRNAs/genetics , RNA, Circular/genetics , RNA, Messenger/geneticsABSTRACT
Objective:To investigate the prognostic value of systemic inflammatory score (SIS) in prognostic assessment of patients with unresectable metastatic colorectal cancer (mCRC).Methods:The clinical data of 130 patients with unresectable mCRC in Affiliated Haikou Hospital of Xiangya Medical College of Central South University from January 2014 to December 2016 were retrospectively analyzed. The relationship between SIS and clinicopathological characteristics of unresectable mCRC patients was also analyzed. The survival analysis was made by using Kaplan-Meier. The risk factors affecting the prognosis of unresectable mCRC patients were analyzed by using Cox regression model to make univariate and multivariate analysis.Results:According to SIS results, patients were divided into 0-score group (40 cases), 1-score group (58 cases), and 2-score group (32 cases). There were no significant differences in different SIS constitution patients stratified by age, gender, primary tumor location, functional status score, tissue type, RAS gene status, number of metastatic organs, peritoneal spread and molecular targeted therapy (all P > 0.05). Kaplan-Meier survival analysis showed that the 5-year overall survival rates of SIS 0-score, 1-score and 2-score group were 37.5%, 19.0%, 6.3%, respectively; and the difference was statistically significant ( χ2 = 3.152, P<0.01). Cox regression survival analysis showed that female, primary tumor location in right side and SIS (scores of 1-2) were independent risk factors for overall survival in patients with unresectable mCRC (all P<0.05). Conclusion:SIS may be an important indicator for prognostic assessment of patients with unresectable mCRC, and patients with high SIS have poor prognosis.
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Objective:To explore the therapeutic efficacy and safety of conventional radiotherapy and large-segment radiotherapy in patients with early breast cancer undergoing breast-conserving surgery.Methods:A total of 84 early breast cancer patients undergoing breast-conserving surgery treated in Haikou People's Hospital from March 2013 to March 2015 were collected, and they were divided into the conventional group (40 cases) and the large segmentation group (44 cases) according to the radiotherapy method. The patients in the conventional group received conventional radiotherapy at a dose of 2 Gy/time, 25 times in total, with a total dose of 50 Gy, 42 d of total treatment; the patients in the large-scale group received large-scale radiotherapy at a dose of 2.66 Gy/time, 16 times in total, with a total dose of 42.56 Gy, 22 d of total treatment. The effect of radiotherapy, cosmetic effect and adverse reactions of patients in two groups was evaluated. The survival, local recurrence and distant metastasis were also analyzed.Results:There was no statistically significant difference in the total effective rate between the large segmentation group and the conventional group [90.9% (40/44) vs. 95.0% (39/40), χ2 = 1.626, P = 0.205], and there was no statistically significant difference in the excellent rate of beauty effect [90.9% (40/44) vs. 92.5% (37/40), χ2 = 0.069, P = 0.792]. There were no significant differences in the incidence of esophageal mucosal reaction, radiation-induced pneumonia, myelosuppression, advanced skin reaction and acute skin reaction between the conventional group and the large-scale group [2.5% (1/40) vs. 4.6% (2/44), χ2 = 0.255, P = 0.614; 2.5% (1/40) vs. 2.3% (1/44), χ2 = 0.005, P = 0.946; 52.5% (21/40) vs. 52.3% (23/44), χ2 = 0.001, P = 0.983; 2.5% (1/40) vs. 2.3% (1/44), χ2 = 0.005, P = 0.946; 85.0% (34/40) vs. 79.6% (35/44), χ2 = 0.425, P = 0.514). There were no significant differences in 3-year overall survival rate, local recurrence rate and distant metastasis rate between the large-scale segmentation group and the conventional group [90.0% vs. 90.9%, χ2 = 0.020, P = 0.904; 5.0% (12/40) vs. 2.3% (1/44), χ2 = 0.453, P = 0.501; 7.5% (3/40) vs. 6.3% (3/44), χ2 = 0.015, P > 0.05]. Conclusions:Compared with conventional segmented radiotherapy, large-segment radiotherapy regimen can achieve similar efficacy and safety when used as an adjuvant treatment for early breast cancer after breast-conserving surgery. It has the advantages of short treatment cycles and fewer radiotherapy treatments.
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Objective:To evaluate the clinical prognosis of patients with pseudomyxoma peritonei (PMP) after cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC).Methods:The clinical data of 42 patients with PMP after CRS combined with HIPEC in the Affiliated Haikou Hospital of Xiangya Medical College of Central South University from January 2012 to December 2018 was retrospectively analyzed. All patients underwent open surgery CRS combined with HIPEC, the operation condition and prognosis of patients were analyzed.Results:In 42 patients with PMP, the disenminated peritoneal adenomucinosis (DPAM) accounted for 61.9% (26/42), the peritoneal mucinous carcinomatosis (PMCA) accounted for 28.6% (12/42), and the borderline accounted for 9.5% (4/42). The incidence rate of major operative complications (grade Ⅲ-Ⅳ) after CRS combined with HIPEC was 21.4% (9/42). The logistic regression analysis showed that the previous surgery score ( OR = 35.765, 95% CI 2.746-43.986, P = 0.001) and completeness of CRS score ( OR = 23.865, 95% CI 1.345-347.876, P = 0.028) were independent factors influencing major postoperative complications in PMP patients. The overall survival time of 42 patients with PMP was (64.8±4.1) months, and the disease-free survival time was (54.0±4.9) months; the 3-year and 5-year overall survival rates were 80.8% and 65.9%, and the 3-year and 5-year disease-free survival rates were 59.5% and 54.6%, respectively. The difference in overall survival time of patients with different pathological subtypes was statistically significant ( P = 0.022). Conclusion:CRS combined with HIPEC is safe and effective for treatment of patients with PMP, and most of the patients have a good prognosis.