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Shaohua Zheng,1,* Lihua Li,2,* Na Li,3 Yi Du,4 Nan Zhang5 1Department of Anesthesiology, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an City, Shanxi Province, 710061, People’s Republic of China; 2Department of Stomatology, North Sichuan Medical College, Nanchong, Sichuan Province, 637000, People’s Republic of China; 3Department of Stomatology, Xi’an Shiyou University Hospital, Xi’an City, Shanxi Province, 710065, People’s Republic of China; 4Jinan Stomatological Hospital, Jinan City, Shandong Province 250001, People’s Republic of China; 5Department of Stomatology, The First Affiliated Hospital of Xi’an Jiaotong University, Xian City, Shanxi Province 710061, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yi DuJinan Stomatological Hospital, Jinan City, Shandong Province 250001, People’s Republic of ChinaEmail yidu1967@163.comNan ZhangDepartment of Stomatology, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an City, Shanxi Province 710061, People’s Republic of ChinaEmail rq6773@163.comIntroduction: Oral squamous cell carcinoma (OSCC) is the most prevalent malignancy affecting the oral cavity and is associated with severe morbidity and high mortality. 1, 6-O, O-Diacetylbritannilactone (OODBL) isolated from the medicinal herb of Inula britannica has various biological activities such as anti-inflammation and anti-cancer. However, the effect of OODBL on OSCC progression remains unclear. Here, we were interested in the function of OODBL in the development of OSCC.Methods: The effect of OODBL on OSCC progression was analyzed by MTT assays, colony formation assays, transwell assays, apoptosis analysis, cell cycle analysis, and in vivo tumorigenicity analysis. The mechanism investigation was performed by qPCR assays, Western blot analysis, and luciferase reporter gene assays.Results: We found that OODBL inhibits the proliferation of OSCC cells in vitro. Moreover, the migration and invasion were attenuated by OODBL treatment in the OSCC cells. OODBL arrested cells at the G0/G1 phase and induced cell apoptosis. OODBL was able to up-regulate the expression of LXRα, ABCA1, and ABCG1 in the system. In addition, OODBL activated LXRα/ABCA1 signaling by targeting miR-1247-3p. Furthermore, the expression levels of cytochrome c in the cytoplasm, cleaved caspase-9, and cleaved caspase-3 were dose-dependently reduced by OODBL. Besides, OODBL increased the expression ratio of Bax to Bcl-2. Moreover, OODBL repressed tumor growth of OSCC cells in vivo.Discussion: Thus, we conclude that OODBL inhibits OSCC progression by modulating miR-1247-3p/LXRα/ABCA1 signaling. Our finding provides new insights into the mechanism by which OODBL exerts potent anti-tumor activity against OSCC. OODBL may be a potential anti-tumor candidate, providing a novel clinical treatment strategy of OSCC.Keywords: OSCC, OODBL, anti-tumor, LXRα/ABCA1 signaling, miR-1247-3p

Liantao Li,1– 4,* Na Li,2,3,* Nianli Liu,1,4 Fuchun Huo,5 Junnian Zheng1,2 1Cancer Institute, Xuzhou Medical University, Xuzhou 221000, People’s Republic of China; 2Center of Clinical Oncology, Affiliated Hospital of Xuzhou Medical University, Xuzhou 221000, People’s Republic of China; 3Department of Radiation Oncology, Affiliated Hospital of Xuzhou Medical University, Xuzhou 221000, People’s Republic of China; 4Jiangsu Center for the Collaboration and Innovation of Cancer Biotherapy, Xuzhou 221000, People’s Republic of China; 5Department of Pathology, Xuzhou Medical University, Xuzhou 221000, People’s Republic of China*These authors contributed equally to this workCorrespondence: Junnian Zheng 84 West Huaihai Road, Xuzhou, Jiangsu, People’s Republic of ChinaTel +8605168558230Email jnzheng@xzhmu.edu.cnPurpose: DNA methylation plays an important role in regulating gene expression. Methyl-CpG-binding domain (MBD) proteins recognize and bind to methylated DNA, which mediate gene silencing by the interaction with deacetylases and histone methyltransferases. MBD2 has been reported in various human cancers; however, its clinical implication and potential regulatory role in renal cell carcinoma (RCC) have not been elaborated.Materials and Methods: In the study, we estimated the expression and prognostic value of MBD2 in RCC cell lines and tissues by Western blotting and immunohistochemistry. The associations of MBD2 expression and pathological characters and survival in RCC patients were performed using χ 2 and Kaplan–Meier survival analysis, respectively. Univariate and multivariable Cox regression analyses suggested the independent predictors in RCC prognosis. The functional role of MBD2 in RCC progression was assessed by in vitro cell experiments. In addition, we identified the MBD2-mediated alterations of protein-related proliferation and EMT markers in RCC cells after MBD2 overexpression and knockdown.Results: We found that the protein levels of MBD2 were upregulated in RCC cells and tissues. High MBD2 expression was related to TNM stage and predicted poorer survival in RCC. Enforced expression of MBD2 significantly promoted the proliferation, cycle progress, invasion and migration of RCC cells in vitro. However, downregulating MBD2 remarkably weakened the above cell functions. Mechanistically, the promotive effect of MBD2 overexpression may be regulated by its effects onp21, p53 and Cyclin D1 expression and EMT process.Conclusion: These results indicated that MBD2confers an oncogenic function in the malignant progression of RCC. MBD2 could be served as a meaningful prognostic biomarker and a latent therapeutic target in RCC patients.Keywords: MBD2, RCC, prognosis

Ran Li1 ,* Jintao Cao1 ,* Liucheng Chen2 ,* Fangqin Cui,3 Shaohua Chen,1 Zhenzhong Feng,1 Nan Li1 1Department of Pathology, The First Affiliated Hospital of Bengbu Medical College, Bengbu Medical College, Bengbu, Anhui, People’s Republic of China; 2Department of Radiology, The First Affiliated Hospital of Bengbu Medical College, Department of Imaging Diagnosis, Medical Imaging College, Bengbu Medical College, Bengbu, Anhui, People’s Republic of China; 3Department of Pathophysiology, Bengbu Medical College, Bengbu, Anhui, People’s Republic of China*These authors contributed equally to this workCorrespondence: Nan LiDepartment of Pathology, The First Affiliated Hospital of Bengbu Medical College, 287 Changhuai Road, Bengbu 233000, Anhui, People’s Republic of ChinaTel +86-552-3070209Email linanangel100@sina.comPurpose: Gastrointestinal neuroectodermal tumors (GNETs) are uncommon malignant tumors derived from ectodermal primitive neural cells.Patients and Methods: We retrospectively analyzed 2 GNET cases at our hospital and the remaining 94 cases in the literature to determine clinicopathological prognostic factors.Results: The patients had a mean age of 36 years and a median tumor size of 4.5 cm. A total of 67.0% of the tumors were located in the small intestine, and 76.4% of the patients presented recurrence or metastasis. There was a significant difference in sex and presence of osteoclast-like cells (P< 0.01). Microscopically, most cells were round or short spindle-like in shape, with weak eosinophilic or clear cytoplasm. Neoplastic cells were always arranged in solid sheets, nests, and pseudoalveoli. Immunohistochemistry showed strong, diffuse S100 and SOX10 expression, with a complete absence of HMB45 and Melan-A expression. A total of 72.9% of the cases revealed genetic EWSR1 recombination, including our 2 cases. The median time to death and first metastasis was 61 months and 12 months, respectively. K-M analysis showed a great difference in survival according to lymph node invasion or distant metastasis (M+N), independent lymph node metastasis (N), lower histological grades (G2), and aggressive chemoradiotherapy (P=0.026, P=0.027, P=0.039 and P=0.037). However, independent T, independent M, and postoperative routine adjuvant therapy showed no statistical influence on overall survival or disease-free survival.Conclusion: GNET is a new entity distinct in its clinical, morphological, immunochemical, and genetic features. Radical excision, close follow-up and adjuvant therapy may be effective for prolonged survival.Keywords: gastrointestinal neuroectodermal tumor, clear cell sarcoma-like tumor, GNET, SWI/SNF

Nan Li,* Jing-Jing Wu,* Ting-Ting Chen, Xiu-Qin Li, Jia-Jia Du, Shan Shan, Wei Wei, Wu-Yi Sun Institute of Clinical Pharmacology, Anhui Medical University, Key Laboratory of Anti-Inflammatory and Immune Medicine, Ministry of Education, Anhui Collaborative Innovation Center of Anti-Inflammatory and Immune Medicine, Hefei 230032, People’s Republic of China*These authors contributed equally to this workCorrespondence: Wu-Yi Sun; Wei WeiInstitute of Clinical Pharmacology, Anhui Medical University, Key Laboratory of Anti-Inflammatory and Immune Medicine, Ministry of Education, Anhui Collaborative Innovation Center of Anti-Inflammatory and Immune Medicine, Meishan Road, Hefei 230032, Anhui Province, People’s Republic of ChinaTel/Fax +86 551 65161206Email sunwuyi51@aliyun.com; wwei@ahmu.edu.cnBackground: Hepatocellular carcinoma (HCC) is an aggressive form of human liver cancer and the fifth most common malignancy worldwide. Novel effective treatment strategies for HCC are urgently in clinical because of its poor response to conventional therapies. G protein-coupled receptor kinases (GRKs), including GRK2 and GRK3, are known that involves in various essential cellular processes and regulates numerous signaling pathways. However, the role of GRK2/3 in invasion and metastasis of HCC still remains unclear.Materials and Methods: Immunohistochemistry, Western blot, laser confocal microscopy and qRT-PCR were used to detect the expression of GRK2/3 and EP2 in liver tissues of HCC patients and DEN-induced HCC mice. Wound healing and transwell assay were applied to measure the migration and invasion of HCC cells after transfected with GRK2 siRNA. The downstream pathway of Akt and ERK was verified by Western blot.Results: The expression of GRK2 was significantly decreased, while GRK3 was not significantly changed in HCC tissues compared with noncancerous tissues of HCC patients. Moreover, GRK2 expression was reduced during liver tumorigenesis in diethylnitrosamine-induced liver tumor model. In addition, our in vitro study showed that GRK2 expression was gradually decreased with increasing HCC cell line metastatic potential, and GRK2 knockdown significantly promoted the migration and invasion of HCC cells. Furthermore, low GRK2 expression was associated with increased expression of EP2 receptor translocation to HCC cell membrane, and the activation of Akt pathway.Conclusion: These data suggest that GRK2 inhibits HCC metastasis and invasion may be through regulating EP2 receptor translocation, and this effect appears to be mediated by Akt pathway.Keywords: GRK2, hepatocellular carcinoma, invasion, migration

Weiwei Huang,1 Chao Li,2 Mulan Chen,1 Duanyu Lin,3 Fan Wu,1 Xinhua Chen,1 Nani Li,1 Lili Wang,1 Jian Liu1 1Department of Medical Oncology, Fujian Cancer Hospital, Fujian Medical University Cancer Hospital, The Teaching Hospital of Fujian University of Traditional Chinese Medicine, Fuzhou, People’s Republic of China; 2Department of Pathology, Fujian Cancer Hospital, Fujian Medical University Cancer Hospital, The Teaching Hospital of Fujian University of Traditional Chinese Medicine, Fuzhou, People’s Republic of China; 3Department of Imaging, Fujian Cancer Hospital, Fujian Medical University Cancer Hospital, The Teaching Hospital of Fujian University of Traditional Chinese Medicine, Fuzhou, People’s Republic of ChinaCorrespondence: Jian Liu Tel +86-13906912727Email ljfjszl@163.comAbstract: A 62-year-old postmenopausal woman was diagnosed with breast cancer in her left breast and received modified radical mastectomy (molecular type: hormone-receptor-positive human epidermal growth factor receptor-2 negative). After that, she received postoperative chemotherapy and radiotherapy. After 2 years of tamoxifen adjuvant endocrine treatment, the patient inccurred recurrence with metastasis. PET-CT scanning showed metastasis in the left thoracic wall, the sixth left rib, and the right lower lobe of the lung. Multiple lymph node metastases were observed throughout the body. Palbociclib in combination with an aromatase inhibitor (AI) was used, but the metastatic lesion at the sixth left rib increased than before. Subsequently, the lesion shrunk and the clinical symptoms were relieved, which was considered as a pseudoprogression. Herein, we reported a pseudoprogression in the breast cancer patient after treatment with palbociclib plus AI.Keywords: pseudoprogression, palbociclib, breast cancer

Bin Han,1 E Shaolong,1 Lan Luan,2 Nanyang Li,2 Xuefeng Liu1 1Department of Urology, Shengjing Hospital of China Medical University, Shenyang, People’s Republic of China; 2Department of Pathology, Central Hospital Affiliated to Shenyang Medical College, Shenyang, People’s Republic of ChinaCorrespondence: Xuefeng LiuDepartment of Urology, Shengjing Hospital of China Medical University, Shenyang, Liaoning 110004, People’s Republic of ChinaEmail xuefengliu78@163.comIntroduction: Accumulating evidence has demonstrated that circular RNAs (circRNAs) play a key role in the tumorigenesis of various types of cancers, including clear cell renal cell carcinoma (ccRCC).Materials and Methods: Reverse transcription-quantitative polymerase chain reaction was used to detect the expression of circRNA homeodomain interacting protein kinase 3 (circHIPK3) and microRNAs (miRNAs), including miR-508-3p. The clinical measurement of circHIPK3 was evaluated by Kaplan–Meier survival analysis and receiver operating characteristic analysis. Cell Counting Kit-8 and Transwell chamber assays were performed to determine the changes in the proliferative and metastatic ability of A498 and 786-O cells. C-X-C motif chemokine ligand 13 (CXCL13) protein expression was detected by Western blot analysis. The targeted binding effect between miR-508-3p and circHIPK3 or CXCL13 was confirmed by constructed luciferase and RNA immunoprecipitation (RIP) assays, respectively. Fluorescence in situ hybridization (FISH) assay was used to measure the subcellular localization of circHIPK3 and miR-508-3p.Results: It was found that circHIPK3 was markedly upregulated in ccRCC tissue and cell lines, and circHIPK3-upregulation was closely correlated with poor clinicopathological features in patients with ccRCC. It was found that both miR-508-3p and circHIPK3 were localized in the cytoplasm of ccRCC cells. The up- and downregulation of circHIPK3 positively regulated ccRCC cell proliferation and metastasis, and this regulatory effect was reversed by miR-508-3p. Through luciferase and RIP assays, it was confirmed that circHIPK3 could interacted with miR-508-3p. Furthermore, it was revealed that CXCL13, which was negatively correlated with miR-508-3p, was upregulated in ccRCC. It was also shown that CXCL13 was a downstream target of miR-508-3p. miR-508-3p suppressed ccRCC cell proliferation and metastasis by targeting CXCL13. Lastly, it was demonstrated that circHIPK3 promoted CXCL13 to facilitate ccRCC cell proliferation and metastasis by decoying miR-508-3p.Conclusion: In brief, the results of the present study showed that circHIPK3 promoted ccRCC cell proliferation and metastasis by altering miR-5083p/CXCL13 signaling. The present findings might provide a novel target for the molecular treatment of ccRCC.Keywords: circHIPK3, miR-508-3p, CXCL13, proliferation, metastasis, ccRCC &nbsp

Niuniu Li,1,* Chun Cheng,2,* Tieyan Wang3 1Department of Gynecology and Obstetrics of Shiyan, Taihe Hospital of Hubei Province, Shiyan, Hubei 442000, People’s Republic of China; 2Department of Pediatrics, Huangshi Central Hospital, Affiliated Hospital of Hubei Polytechnic University, Edong Healthcare Group, Huangshi, Hubei 435000, People’s Republic of China; 3Clinical Pathology Department of Shiyan, Taihe Hospital of Hubei Province, Shiyan, Hubei 442000, People’s Republic of China*These authors contributed equally to this workCorrespondence: Tieyan Wang Email tieyan_wang@sina.comBackground: Cervical cancer (CC) is a highly prevalent cancer and one of the main causes of death among women worldwide. The miR-181 family has turned out to be associated with tumorigenesis in a variety of tumors by regulating the expression of tumor-related genes. However, the mechanisms and biological function of miR-181c-5p in cervical squamous cell carcinoma (SCC) have not been well elucidated.Materials and Methods: SiHa cell lines with specific gene overexpression vectors were constructed. Targetscan was used to predict the binding site of miR-181c-5p and GSKIP. MTT assay was used to detect the clone formation rate. Flow cytometry was used to detect the apoptosis rate and to separate the cell markers. The Transwell test was used to detect cell invasion. Immunohistochemistry was used to detect protein expression in tumor tissues. Western Blotting was used to detect the expression levels of related proteins.Results: GSKIP was predicted to be the target gene of miR-181c-5p in cervical SCC. MiR-181c-5p overexpression suppressed SiHa cells proliferation and promoted apoptosis; the protein expressions of Ki67 and PCNA were decreased, but the expressions of Caspase-3 and Bax/Bcl-2 were increased. The overexpression of miR-181c-5p inhibited the stem-like properties of SiHa cells; the expressions of SOX2, OCT4 and CD44 were decreased. Furthermore, miR-181c-5p upregulation limited the invasion of SiHa cells; the expression of E-cadherin was higher, but the expressions of N-cadherin and Vimentin were lower. MiR-181c-5p overexpression inhibited tumorigenesis in cervical SCC tissues; the expressions of Ki67, Caspase-3, CD44 and Vimentin in vivo were consistent with those in vitro.Conclusion: Taken together, miR-181c-5p was able to mitigate the cancer cell characteristic and invasive properties of cervical SCC through targeting GSKIP gene.Keywords: apoptosis, cancer stem cell, epithelial-mesenchymal transition, kinase 3β interaction protein, miR-181c-5p

Xuesen Li,1 Na Li,2 Qinghui Niu,3 Haibin Zhu,4 Zhijie Wang,1 Qingxian Hou1 1Department of Spine Surgery, The Affiliated Hospital of Qingdao University, Qingdao, Shandong 266555, People’s Republic of China; 2Department of Ophthalmology, The Affiliated Hospital of Qingdao University, Qingdao, Shandong 266555, People’s Republic of China; 3Department of Hepatic Medicine, The Affiliated Hospital of Qingdao University, Qingdao, Shandong 266555, People’s Republic of China; 4Department of Orthopedics and Traumatology, Traditional Chinese Medical Hospital of Huangdao District, Qingdao, Shandong 266500, People’s Republic of ChinaCorrespondence: Qingxian HouDepartment of Spine Surgery, The Affiliated Hospital of Qingdao University, No. 1677, Wutaishan Road, Qingdao, Shandong 266555, People’s Republic of ChinaTel/Fax +86 532 82919525Email qingxiar547@163.comPurpose: Osteosarcoma (OS) is an invasive bone tumor that primarily affects children and adolescents. MicroRNA-629 (miR-629) acts as an oncogene involved in the development of various cancers. This study aims to reveal the clinical significance and biological function of miR-629 in OS.Patients and Methods: The levels of miR-629 expression in tissues and cells were detected through quantitative real-time polymerase chain reaction (qRT-PCR). Chi-square test was used to evaluate the relationship between miR-621 expression and clinical parameters in patients with OS. Survival analysis was performed by the Kaplan–Meier method. Cox regression analysis of the effect of miR-629 expression on the prognosis of OS patients. CCK-8 and Transwell experiments were used to demonstrate the effect of miR-629 on OS cell function.Results: Compared with the controls, miR-629 levels were significantly elevated in patients with OS (P < 0.001), Furthermore, miR-629 upregulation showed significantly associated with clinical stage (P = 0.011), distant metastasis (P = 0.003) and poor survival (log rank test, P = 0.013) in OS patients. miR-629 might be a potential prognostic biomarker for OS (HR = 2.890, 95% CI = 1.126– 7.416, P = 0.027). Cell function experiments proved that the high expression of miR-629 promoted cell proliferation, migration, and invasion of OS.Conclusion: All experimental results demonstrated that miR-629 as an oncogene promotes the tumor cell growth, migration and invasion of OS, and miR-629 may act as a novel prognostic biomarker and therapeutic target for patients with this malignant tumor.Keywords: miR-629, prognosis, progression, osteosarcoma

Na Li,1 Xinlu Liu2 1 1st Department of Gastroenterology, First Affiliated Hospital of Dalian Medical University, Dalian 116011, People’s Republic of China; 2 1st Department of General Surgery, First Affiliated Hospital of Dalian Medical University, Dalian 116011, People’s Republic of ChinaCorrespondence: Xinlu Liu 1st Department of General Surgery, First Affiliated Hospital of Dalian Medical University, Dalian 116011, People’s Republic of ChinaTel +86-411-83635963-2073Fax +86-411-83635432Email liuxinlu86@163.comAbstract: Phosphoglycerate mutase 1 (PGAM1) is an important enzyme that catalyzes the reversible conversion of 3-phosphoglycerate and 2-phosphoglycerate during the process of glycolysis. Increasing evidence suggests that PGAM1 is widely overexpressed in various cancer tissues and plays a significant role in promoting cancer progression and metastasis. Although PGAM1 is a potential target in cancer therapy, the specific mechanisms of action remain unknown. This review introduces the basic structure and functions of PGAM1 and its family members and summarizes recent advances in the role of PGAM1 and various inhibitors of cancer cell proliferation and metastasis from a glycolytic and non-glycolytic perspective. Recent studies have highlighted a correlation between PGAM1 and clinical features and prognosis of cancer as well as the development of target drugs for PGAM1. The integrated information in this review will help better understand the specific roles of PGAM1 in cancer progression. Furthermore, the information highlights the non-glycolytic functions of PGAM1 in tumor metastasis, providing an innovative basis and direction for clinical drug research.Keywords: PGAM1, glycolysis, non-glycolytic, proliferation, metastasis, cancer therapy

Liang-Yu Bie,1 Ning Li,1 Wen-Ying Deng,1 Xiao-Yu Lu,2 Ping Guo,3 Su-Xia Luo1 1Department of Oncology, Affiliated Cancer Hospital of Zhengzhou University/Henan Cancer Hospital, Zhengzhou 450008, Henan Province, People’s Republic of China; 2Department of Pathology, Affiliated Cancer Hospital of Zhengzhou University/Henan Cancer Hospital, Zhengzhou 450008, Henan Province, People’s Republic of China; 3Department of Oncology, The First Affiliated Hospital of Nanyang Medical College, Nanyang 473061, People’s Republic of ChinaCorrespondence: Su-Xia LuoDepartment of Oncology, Affiliated Cancer Hospital of Zhengzhou University/Henan Cancer Hospital, No. 127 Dongming Road Jinshui District, Zhengzhou 450008, Henan Province, People’s Republic of ChinaEmail luosuxia000@qq.comPurpose: miR-191 and miR-425 have been proved to be highly expressed in gastric carcinoma (GC). However, little research has been done on their clinical value in serum of patients with advanced GC. In addition, it is not clear whether they can be used as markers for the response and prognosis of GC patients treated with oxaliplatin combined with 5-fluorouracil and FOLFOX chemotherapy.Patients and Methods: A total of 230 patients with advanced GC admitted to our hospital were selected as the study objects, all of whom received FOLFOX chemotherapy regimen. Another 100 cases of healthy subjects were included. QRT-PCR was employed to detect the serum expression of miR-191 and miR-425 in patients.Results: Compared with the healthy subjects, the serum expressions of miR-191 and miR-425 in GC patients were significantly upregulated, which were correlated with differentiation degree and TNM staging, respectively. According to the ROC curve, the AUC of miR-191 and miR-425 for GC diagnosis was 0.937 and 0.901, respectively, while the AUC for differentiation degree diagnosis was 0.854 and 0.822, and that for TNM staging diagnosis was 0.860 and 0.829, respectively. The predictive AUC of miR-191 and miR-425 for chemosensitivity was 0.868 and 0.835, respectively, with a combined predictive AUC of 0.935. Low differentiation degree, high TNM staging, high miR-191 and high miR-425 expressions were independent risk factors for chemotherapy insensitivity. Differentiation degree, TNM staging, chemotherapy effect, miR-191 and miR-425 were independent influencing factors for the prognosis of GC patients.Conclusion: Up-regulated expression of miR-191 and miR-425 in the serum of patients with advanced GC are effective biomarkers for the diagnosis, chemotherapy and prognosis evaluation of GC.Keywords: miR-191, miR-425, FOLFOX, chemotherapy, prognosis, GC

Min Wu,1 Zhaobo Liu,1 Xin Li,1 Aiying Zhang,2 Ning Li1,2 1Department of General Surgery, Beijing Youan Hospital, Capital Medical University, Beijing, People’s Republic of China; 2Beijing Institute of Hepatology, Beijing Youan Hospital, Capital Medical University, Beijing, People’s Republic of ChinaCorrespondence: Ning LiBeijing Institute of Hepatology, Beijing Youan Hospital, Capital Medical University, 8 Xitoutiao, Youanmenwai, Fengtai District, Beijing 100069, People’s Republic of ChinaEmail liningya@ccmu.edu.cnAiying Zhang Email zhangaiying1996@163.comObjective: This study aimed to evaluate the individual and combined diagnostic values of serum alpha-fetoprotein (AFP), des-gamma-carboxyprothrombin (DCP), glypican-3 (GPC3) and golgi protein 73 (GP73) in diagnosing hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC).Methods: Participants from Beijing YouAn Hospital were enrolled and divided into seven groups. Serum was collected and the levels of AFP, GPC3, GP73 and DCP were simultaneously measured with a protein array. Pearson’s χ2 test was applied to compare the clinicopathological characteristics. Receiver operating characteristic (ROC) curves were used to analyse the diagnostic performance of the four markers.Results: As a single biomarker for differentiating HCC from all controls, AFP had a larger area under the curve (AUC) (0.798, 95% CI (0.754– 0.838) than the other biomarkers, with a sensitivity of 77.3% and a specificity of 71.1%. Among the other combinations, AFP plus GPC3 and DCP (0.871, 95% CI (0.833– 0.903)) was the best at differentiating HCC from all controls. In discriminating very early stage and early stage HCC from all controls, the AUC of GPC3 (0.744, 95% CI (0.690– 0.793); sensitivity 62.8%; specificity 83.3%) was better than that of AFP (0.723, 95% CI (0.668– 0.774); sensitivity 67.3%; specificity 71.7%). Among all biomarker combinations, the combination of AFP, GPC3 and GP73 had the largest AUC (0.843, 95% CI (0.796– 0.883); sensitivity 84.1%; specificity 71.7%). AFP (AUC 0.726, 95% CI (0.662– 0.784)) showed the best performance in the very early diagnosis of HBV-related HCC.Conclusion: As a single biomarker, AFP has an advantage in the very early and early diagnosis of HBV-related HCC. The combination of AFP, GPC3 and GP73 is the most suitable marker for the early diagnosis of HBV-related HCC. However, AFP remains the best biomarker for the very early diagnosis of HBV-related HCC, and the adding of one or more markers does not significantly improve the diagnostic accuracy.Keywords: hepatocellular carcinoma, hepatitis B virus, diagnosis, protein array

Ziyan Yang,1,* Nani Li,2,* Xiaolin Li,3 Lei Lei,3 Xiaojia Wang3 1The Second Clinical Medical College of Zhejiang Chinese Medical University, Hangzhou, Zhejiang 310022, People’s Republic of China;2Department of Medical Oncology, Fujian Cancer Hospital, Fuzhou, Fujian 350014, People’s Republic of China; 3Department of Medical Oncology, Cancer Hospital of the University of Chinese Academy of Sciences, Hangzhou, Zhejiang, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xiaojia WangDepartment of Medical Oncology, Cancer Hospital of the University of Chinese Academy of Sciences, Hangzhou, Zhejiang 310022, People’s Republic of ChinaTel +86 13906500190Email wxiaojia0803@163.comBackground: Hormone receptor (HR) and human epidermal growth factor receptor (HER2) discordance between primary and metastatic breast cancer lesions is common. However, its impact on long-term survival remains unclear. We aimed to determine the prognostic value of this discordance in patients with metastaticf breast cancer (MBC).Methods: A total of 270 patients with MBC who were underwent re-biopsy of progressive metastases at Zhejiang Cancer Hospital from January 1, 2012 to December 31, 2015 with patients consent and then review their primary tumors pathological findings. The HR and HER2 status in both primary and progressive metastatic lesions was determined by immunohistochemistry and/or fluorescence in situ hybridization. The discordance rates were correlated with the clinicopathologic characteristics, metastatic lesions, salvage treatment, and survival analysis in this population.Results: A total of 142 (52.6%) MBC patients were diagnosed with discordant HR and HER2 status. Alterations in estrogen receptor (ER), progesterone receptor (PR), and HER2 status were observed in 20.70%, 37.78%, and 11.48% cases, respectively. Chemotherapy (P=0.0192) and endocrine therapy (P=0.048) significantly affected the conversion of HR status. Endocrine therapy was positively correlated with PR discordance (P=0.002), while ER discordance was associated with adjuvant chemotherapy (P=0.031). Survival analysis showed that ER status alterations between primary and metastatic lesions were associated with overall survival (P=0.002). The clinical prognosis was significantly worse with HR losses than with persistent HR positivity (P=0.023). In Cox multivariate analysis, the loss of HR expression and conversion to triple negative were independent prognostic indicators.Conclusion: Discordance in HR status between primary and metastatic lesions may impact the prognosis of MBC, and HR conversion has independent prognostic value.Keywords: breast cancer, hormone receptor, receptor discordance, recurrent

Li Yao,1,* Linghui Zhou,2,3,* Yujiao Deng,2,3,* Yi Zheng,2,3 Pengtao Yang,2 Meng Wang,2 Shanshan Dong,4 Qian Hao,2,3 Peng Xu,2,3 Na Li,2,3 Ying Wu,2,3 Zhen Zhai,2,3 Lijuan Lyu,2,3 Zhijun Dai2,3 1Department of Neurology, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710004, People’s Republic of China; 2Department of Oncology, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710004, People’s Republic of China; 3Department of Breast Surgery, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, People’s Republic of China; 4School of Life Science and Technology, Xi’an Jiaotong University, Xi’an 710049, People’s Republic of China*These authors contributed equally to this workCorrespondence: Zhijun DaiDepartment of Oncology, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710004, People’s Republic of ChinaEmail dzj0911@126.comBackground: Thymidylate synthase (TYMS) polymorphisms are reported to be related to susceptibility to some cancers. However, no study exists on TYMS polymorphisms and glioma risk. This study aimed to evaluate the relationship between two common TYMS gene variants (rs1059394 C>T, rs2847153 G>A) and glioma susceptibility.Methods: This case-control study included 605 patients and 1300 cancer-free individuals. Genotyping was performed using Sequenom Mass-ARRAY. We determined odds ratios (ORs) and their 95% confidence intervals (CIs) to estimate the correlations.Results: The analysis revealed that rs1059394 TT and CT+TT genotype had significantly low glioma risk (TT to CC: OR = 0.71, 95% CI = 0.52–0.97, P = 0.03; CT+TT to CC: OR = 0.74, 95% CI = 0.55–0.99, P = 0.04). However, no significant difference was found between rs2847153 and glioma risk in any genetic model (P﹥0.05). In high-grade gliomas, the GA and GA+AA genotypes of rs2847153 made the majority of genotypes, compared with GG genotype (GA to GG: OR = 2.01, 95% CI = 1.39–2.91, P < 0.001; GA+AA to GG: OR = 1.78, 95% CI =1.25–2.54, P < 0.001). Moreover, online expression quantitative trait locus (eQTL) analysis indicated that these two polymorphisms may alter TYMS gene expression in transformed fibroblast cells.Conclusion: Our study provides evidence of the effect of TYMS rs1059394 on the susceptibility of glioma. In high-grade gliomas, compared with GG genotype, the GA and GA+AA genotypes of rs2847153 comprise a larger proportion.Keywords: TYMS, glioma, gene variant, susceptibility, case-control study

Ning Li,1 Tao Cui,2 Wenling Guo,1 Dianwei Wang,1 Li Mao31Obstetrical Department, Binzhou Central Hospital, Binzhou, Shandong 251700, People’s Republic of China; 2Anesthesiology Department, Huimin County Maternal and Child Health Hospital, Binzhou, Shandong, 251700, People’s Republic of China; 3Gynecology Department, Binzhou Central Hospital, Binzhou, Shandong 251700, People’s Republic of ChinaBackground: The dysregulation of microRNAs has been implicated in the progression of different malignancies. Herein, we sought to identify the precise roles of miR-155-5p in the progression of cervical cancer.Materials and methods: The expressions of miR-155-5p in cervical carcinoma cells and clinical tissues were assessed using qRT-PCR analysis. The functions of miR-155-5p on the growth of cervical cancer cell were investigated using MTT and colony formation. The Transwell and wound closure assays were selected to explore the influence of miR-155-5p on the invasion and migration of cervical cancer cell. The effect of miR-155-5p on cervical carcinoma cell growth and metastasis in vivo was investigated using xenograft model and experimental lung metastasis model. Bioinformatics analysis and luciferase reporter assay were applied to identify that tumor protein p53-inducible nuclear protein 1 (TP53INP1) was the target of miR-155-5p.Results: MiR-155-5p was significantly upregulated in cervical cancer tissue than that in control normal tissue. Downexpression of miR-155-5p decreased the growth, migration as well as invasiveness abilities of cervical cancer cell in vitro whereas overregulation of miR-155-5p caused the opposite outcomes. In addition, the in vivo mice xenograft model suggested that downexpression of miR-155-5p restrained the progression of cervical cancer cell whereas overexpression of miR-155-5p caused opposite outcomes. Furthermore, we revealed that TP53INP1 was the target of miR-155-5p and the level of TP53INP1 was inversely associated with miR-155-5p level in cervical carcinoma. Furthermore, TP53INP1 knockdown mimicked the influence of miR-155-5p on cervical cancer proliferation, migration and invasion phenotypes. Finally, overexpression of TP53INP1 impaired the promote effect of miR-155-5p on cervical cancer cell and downregulation of TP53INP1 counteracted the suppressive impact of miR-155-5p on the aggressiveness of cervical cancer cell.Conclusion: Our study indicated that miR-155-5p regulated the development of cervical cancer cell by regulating the expression of TP53INP1.Keywords: miR-155-5p, cervical cancer, TP53INP1, metastasis &nbsp

Nan Li, Guang-Wei Tian, Ling-Rong Tang, Guang Li Department of Radiation Oncology, The First Affiliated Hospital of China Medical University, Shenyang, China Purpose: Human males absent on the first (hMOF) is a histone acetyltransferase (HAT) and is responsible for acetylating histone H4 at lysine 16 (H4K16). Recent studies have indicated that hMOF is overexpressed in non-small-cell lung cancer (NSCLC) as an oncogene. The aim of this study is to profile the prognostic roles of hMOF in patients with unresectable stage III NSCLC undergoing definitive radiotherapy (RT) and in the radiosensitivity of human NSCLC cells. Materials and methods: The expression of hMOF was detected in 24 normal and tumor-paired fresh-frozen NSCLC tissue samples. The immunohistochemistry was conducted, and the correlation of hMOF with clinicopathological parameters was studied in tissues from 90 patients with unresectable stage III NSCLC who underwent definitive RT. Radiation sensitivity was monitored using clonogenic assays in NCI-H1299 and A549 NSCLC cell lines with hMOF knockdown. Results: hMOF was overexpressed in NSCLC tissues compared with non-cancerous tissues. Compared to patients with downregulated hMOF, upregulated hMOF was observed in 51.1% (46/90) of the patients, who showed a significantly worse 5-year survival rate (5.4% vs 22.9%, P=0.025). hMOF expression was an independent prognostic factor of unresectable stage III NSCLC patients who underwent definitive RT. Silencing hMOF increased in vitro the sensitive enhancing ratio (SER) of NSCLC cell lines and downregulated the expression of phospho-ataxia telangiectasia mutated (p-ATM) and RAD51 after irradiation (IR). Conclusion: Overexpression of hMOF predicts poor prognosis in patients with unresectable stage III NSCLC undergoing definitive RT. Downregulating hMOF might be a promising intervention to improve the outcome after RT. Keywords: prognosis, NSCLC, hMOF, radiosensitivity, HATs

Na Li,1 Guodong Wang,2 Xiaohong Jiang,1 Minguang Huang,2 Huanyong Tian,2 Feng Xuan,2 Yufeng Zhang,2 Yanting Lv,3 Mengjun Hu,3 Zhen Wang,2 Peng Ren,1 Maoyi Xu2 1Department of Pathology, Jiaxing University Afffiliated Women and Children Hospital, Jiaxing Maternity and Child Health Care Hospital, Jiaxing University, Jiaxing, Zhejiang314051, China; 2Department of Radiotherapy Oncology, Zhuji People’s Hospital of Zhejiang Province, The Zhuji Affiliated Hospital of Wenzhou Medical University, Zhuji, Zhejiang 311800,China; 3Department of Pathology, Zhuji People’s Hospital of Zhejiang Province, The Zhuji Affiliated Hospital of Wenzhou Medical University, Zhuji, Zhejiang311800, China Abstract: Merkel cell carcinoma (MCC) is a rare, aggressive skin malignancy that has a propensity for local recurrence and metastasis to the lymph nodes. In this case report, we discuss a 54-year-old female with rheumatoid arthritis (RA) who had received treatment with prednisone (15 mg/day) for symptom relief and management. The patient visited our hospital with complaints of a nodule in right preauricular area. Computed tomography (CT) scans revealed no distant metastasis. The patient underwent surgical resection and histopathological evaluation of the nodule led to the diagnosis of MCC. The patients received post-surgical treatment with 6 MeV electronic wire radiotherapy. Six months later, CT of the head, neck, abdomen and chest demonstrated a right cervical lymph node mass at the C2 level. The patient then underwent cervical lymph node biopsy and pathological diagnosis confirmed metastatic MCC. One month after the lymph node biopsy, the patients received postoperative intensity modulated radiation therapy in the biopsied area. The patient did not experience any adverse effects to the therapy. In conclusion, the MCC patients with RA can tolerate radiation therapy. As MCC is a highly malignant neoplasia, considering the immune checkpoint inhibitors can lead to immune-related adverse events, detection of MCC at earlier stages is associated with better survival. The treatment decisions of MCC patients with RA continues is still challenging. Keywords: Merkel cell carcinoma, metastasis, cervical lymph node, rheumatoid arthritis

Na Li,1,2 Mingming Cui,2 Ping Yu,1 Qiang Li1 1Department of Endocrinology and Metabolism, The 2nd Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150080, China; 2Department of Internal Medicine, Harbin Medical University Cancer Hospital, Harbin Medical University, Harbin, Heilongjiang 150081, China Background: Cervical lymph node metastasis is an important prognostic indicator for papillary thyroid carcinoma (PTC) and affects treatment strategies for PTC. lncRNAs essentially contribute to the biological functions of tumors. This study aimed to identify the lncRNAs associated with cervical lymph node metastasis and prognosis of PTC and their potential pathophysiological mechanisms. Materials and methods: PTC-associated lncRNAs were selected from The Cancer Genome Atlas database, and correlations among lncRNAs, lymph node metastasis, tumor staging, and prognosis of PTC were analyzed in silico. These correlations were then validated through quantitative reverse transcription PCR (qRT-PCR) and immunohistochemistry (IHC). Results: In silico analysis showed that FAM95B1 and UCA1 were significantly correlated with cervical lymph node metastasis, tumor staging, and PTC prognosis (P

Wenhua Ma,1,* Fugang Zhao,2,* Changpeng Zhou,1 Yongqian Zhang,1 Yingchun Zhao,1 Na Li,1 Peng Xie3 1Department of Oncology, The First Hospital of Hebei Medical University, Shijiazhuang 050000, Hebei Province, China; 2Department of Traditional Chinese Medicine, The First Hospital of Hebei Medical University, Shijiazhuang 050000, Hebei Province, China; 3Department of Nuclear Medicine, The Third Hospital of Hebei Medical University, Shijiazhuang 050000, Hebei Province, China *These authors contributed equally to this work Aim: To evaluate efficacy and safety of lapatinib or trastuzumab alone or both plus chemotherapy for the treatment of breast cancer patients with positive HER-2 expression.Methods: Cochrane Central Register of Controlled Trials, PubMed, MEDLINE, OVID, Embase, Chinese Biomedical Literature Database, and China Academic Journals Database were searched from 1994 through December 2017 using the keywords “breast cancer”, “preoperative”, “neoadjuvant”, “lapatinib”, “pertuzumab”, “Herceptin”, and “trastuzumab”.Results: Meta-analysis found that pathological complete response (PCR; risk ratio [RR]=0.82, 95% CI: 0.72–0.93) and tall PCR (tPCR; RR=0.77, 95% CI: 0.67–0.88) of chemotherapy plus lapatinib were significantly less effective or safe compared to that of chemotherapy plus trastuzumab (P0.05). Incidence of diarrhea, hepatic toxicity, and skin rash in the groups of chemotherapy plus lapatinib or chemotherapy plus both lapatinib and trastuzumab was significantly higher than that in chemotherapy plus trastuzumab (P

Xiaofei Wang,1 Lei Wang,1 Yanbing Gong,2 Zhenzhen Liu,3 Yingchao Qin,4 Jia Chen,1 Ningcheng Li1 1Department of Urology, Peking University Shougang Hospital, Beijing 100144, People’s Republic of China; 2Department of Science Research, Peking University Shougang Hospital, Beijing 100144, People’s Republic of China; 3Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Hepatopancreatobiliary Surgery Department I, Peking University Cancer Hospital and Institute, Beijing 100142, People’s Republic of China; 4Department of General Surgery, Chaoyang District Shuangqiao Hospital, Beijing 100024, People’s Republic of China Purpose: Long noncoding RNAs (lncRNAs) play an important role in the tumorigenesis and progression of human cancer. This research was performed to investigate the role of LINC01296 in clinical characteristics, biological functions and molecular mechanisms of bladder cancer. Materials and methods: In this study, expressions of LINC01296 in cancer tissues and normal tissues were firstly compared using the Gene Expression Profiling Interactive Analysis database. Subsequently, a microarray data analysis was performed to compare lncRNA and mRNA expression profiles in four pairs of human bladder cancer samples. Then, quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect the expression of LINC01296 in bladder cancer tissues. The association between LINC01296 expressions and clinicopathological characteristics of bladder cancer was analyzed by Kaplan–Meier analysis and the Cox proportional-hazard model. The biological functions and molecular mechanisms of LINC01296 in bladder cancer were studied by MTT assay, colony-formation assay, cell cycle analysis, transwell migration assay, wound healing assay, qRT-PCR analysis and Western blot assay. Results: The expression of LINC01296 was significantly higher in most cancer tissues than that in adjacent normal tissues, and was positively correlated with clinical stages of the cancer (P=0.016), lymph node metastasis (P=0.034), and pathologic grades (P=0.012). The increased level of LINC01296 was associated with a poorer prognosis and shorter survival of the patients. Multivariate analysis showed that the LINC01296 expression was an independent predictor of overall survival in bladder cancer. Additionally, LINC01296 knockdown inhibited the proliferation, migration and progression of cell cycle of bladder cancer cells, and was involved in the regulation of epithelial-mesenchymal transition. Conclusion: The findings of this study suggested that LINC01296 promotes progression of bladder cancer, and potentially acts as a biomarker and therapeutic target of bladder cancer. Keywords: bladder cancer, long noncoding RNA, biological function, biomarker, therapeutic target

Qianqian Yu,1 Niankai Zhang,1 Yan Jiang,1 Yichuan Huang,1 Yuan-Yuan Lian,1 Tingting Liu,1 Na Li,1 Ge Guan2 1Department of Otorhinolaryngology, Affiliated Hospital of Qingdao University, Qingdao, China; 2Department of Organ Transplantation, Affiliated Hospital of Qingdao University, Qingdao, China Background: Nasopharyngeal carcinoma (NPC) is a poorly differentiated malignant tumor, and 5-fluorouracil (5-FU) is one of the most effective chemotherapeutic drugs used for the treatment of NPC. Abnormal expression of RGS17 had been shown to improve the sensitivity of many cancers to chemotherapy; however, the effects of RGS17 on NPC remain unclear. Methods: We cultured NPC cell lines and altered the RGS17 expression with vector. Subsequently colony formation assays and CCK8 cell viability assay was used to test the proliferation of NPC cells, flow cytometry was used to determine the percentage of apoptotic cells, MMP kit and flow cytometry was used to measure the mitochondrial membrane potential, and a xenograft tumour model was attached to investigate the effects of RGS17 on the growth of NPC cells in vivo. Additionally, RT-PCR and western blot was induced to examine the expression of RGS17 and the mechanism. Results: Here, we report for the first time that RGS17 is downregulated in NPC cell lines and that RGS17 overexpression significantly reduces cell proliferation, decreases the mitochondrial membrane potential, and induces cell apoptosis in NPC cells. In vivo, RGS17 also inhibits the tumorigenicity of NPC. In addition, RGS17 could significantly improve the sensitivity of NPC cells to 5-FU. Furthermore, investigation into the underlying mechanisms showed that RGS17 upregulated the levels of IRE1α, p53, and active caspase-3 and cleaved PARP. Conclusion: These results indicate that RGS17 could play important roles in the proliferation, apoptosis, and chemotherapeutic sensitivity of NPC cells. Keywords: nasopharyngeal carcinoma, RGS17, cell apoptosis, mitochondrial membrane potential, fluorouracil chemotherapy

Yangfan Du,1 Na Li,1 Xin Jiao,2 Kai Li,1 Shunchao Yan1 1Department of Oncology, Shengjing Hospital of China Medical University, Shenyang 110022, People’s Republic of China; 2Department of Respiratory Medicine, Shenyang Chest Hospital, Shenyang 110044, People’s Republic of China Purpose: The predictive ability of plasma ESR1 mutations for outcomes among patients with advanced breast cancer undergoing endocrine therapy (ET) remains disputable. We performed a comprehensive meta-analysis of published studies to clarify the impact of plasma ESR1 mutations on clinical outcomes for patients after subsequent ET. Materials and methods: An electronic search was performed to identify eligible studies. Studies analyzing progression-free survival (PFS) and/or overall survival (OS) according to plasma ESR1 mutation status after subsequent ET were included. HRs were calculated using a fixed- or random-effects model according to heterogeneity. Pooled HRs and 95% CIs were used to estimate the effects. Results: Six studies including 705 patients with advanced breast cancer met the inclusion criteria. The impact of plasma ESR1 mutations on PFS and OS after subsequent ET was reported in six studies (seven groups) and two studies, respectively. Meta-analysis results showed that the pooled HR for ESR1 mutations was 1.70 (95% CI, 1.05–2.74; P=0.03) for OS, which was statistically significant for predicting poor survival, and 1.56 (95% CI, 1.13–2.14; P=0.006) for PFS; however, Begg’s and Egger’s test results identified the presence of bias. The trim-and-fill method was used, and after incorporation of the imputed studies, the HR was 1.16 (95% CI, 0.88–1.53, P=0.30) for PFS, which indicates that plasma ESR1 mutation had no effect on PFS after subsequent ET. Subgroup analysis suggested that plasma ESR1 mutations were correlated with shorter PFS (HR, 1.98; 95%CI, 1.12–3.51; P=0.02) in patients subsequently treated with aromatase inhibitors (AIs), whereas no association with PFS was observed for patients subsequently treated with non-AI ET (HR, 1.08; 95% CI, 0.85–1.38; P=0.54) or fulvestrant (HR, 1.03; 95% CI, 0.79–1.34; P=0.83). Conclusion: The current meta-analysis demonstrates that plasma ESR1 mutation status is not a predictor of ET efficacy for all drugs without distinction in patients with hormone-receptor-positive advanced breast cancer. ESR1 mutation predicted a poor response to AIs, whereas it was not predictive of non-AI ET efficacy, especially for fulvestrant. Keywords: ESR1 mutation, breast cancer, endocrine therapy, efficacy predictor

Weiqun Lu,1,2 Zhiliang Huang,1,2 Nan Li,1,2 Haiying Liu1,2 1Department of Gastrointestinal Surgery, 2Guangzhou Key Laboratory of Translational Medicine on Malignant Tumor Treatment, Affiliated Cancer Hospital & Institute of Guangzhou Medical University, Guangzhou, People’s Republic of China Aim: The principal goal of this meta-analysis is to test the hypothesis that circulating total adiponectin or certain fractions may represent a promising biological candidate in modulating the risk of colorectal cancer. Methods: The processes of paper identification, paper selection and data extraction were accomplished independently by two authors. Effect-size estimates were expressed as weighted mean difference (WMD) and 95% confidence interval (95% CI). A total of 31 papers including 48 qualified studies (7,554 patients with colorectal cancer and 9,798 controls) were meta-analyzed. Results: Pooling all studies found that circulating total adiponectin was significantly lower in patients with colorectal cancer than in controls (WMD: -0.76 µg/mL, 95% CI: -1.20 to -0.32, p=0.001), with significant heterogeneity (I2: 94.2%) and low publication bias (Egger’s p=0.336). By adiponectin fractions, the difference in high-molecular weight (HMW) adiponectin was comparable between the two groups (WMD: -0.22 μg/mL, 95% CI: -0.70 to 0.25, p=0.350), while non-HMW adiponectin was significantly lower in patients with colorectal cancer than in controls (WMD: -0.27 µg/mL, 95% CI: -0.35 to -0.19, p

Nan Li,1 Liang Yang,2 Xinna Deng,3 Yanan Sun4 1Department of Gynecology, Second Hospital of Hebei Medical University, Shijiazhuang, People’s Republic of China; 2Department of Neurosurgery, Second Hospital of Hebei Medical University, Shijiazhuang, People’s Republic of China; 3Department of Oncology & Immunotherapy, Hebei General Hospital, Shijiazhuang, People’s Republic of China; 4Department of Obstetrics and Gynecology, Bethune International Peace Hospital of PLA, Shijiazhuang, People’s Republic of China Background: Ovarian cancer is one of the most fatal gynecologic malignancies, with most patients diagnosed at the late stage due to insidious onset and lack of early onset specific symptoms. Previous studies have implied that isoliquiritigenin (ILQ) is a promising chemopreventive agent against oral cancer. Aim: This study aimed to investigate effects of ILQ and elucidate the related mechanism. Materials and methods: Ovarian cancer cell lines, SKOV3 and OVCAR3, were treated with various concentrations of ILQ to detect the dose-dependent effects of ILQ and select the suitable concentration. CCK8 assay and clone formation efficiency assays were used to detect viability and proliferation. The cell migration, invasion, and apoptosis were evaluated by wound healing assays, transwell, and flow cytometry assays. The expression of apoptosis-related proteins (Caspase-3, Caspase3-p17, Bcl-2, Bax, and Bim) and related-signaling pathway proteins were also detected by Western blot. Results: It was observed that the treatment of ILQ inhibited the survival and proliferation of SKOV3 and OVCAR3 cells. ILQ treatment inhibited migration and invasion, and induced apoptosis in SKOV3 and OVCAR3 cells. Also, the ILQ treatment increased the Bax/Bcl-2 ratio in SKOV3 and OVCAR3 cells, suggesting that a mitochondrial apoptotic pathway was triggered. It was also observed that, after treated with ILQ, the phosphorylated form of Akt and mTOR decreased and the expression of GSK3β increased, while P70/S6K decreased. ILQ treatment also decreased the expression of Wnt3a and, therefore, caused the decrease of phosphorylated ERK. ILQ also suppressed the PI3K/Akt/mTOR pathway by reduced the expression level of p-Akt, p-mTOR, P70/S6K and Cyclin D1 in Ishikawa and ES-2 cells. Conclusion: The data suggested that ILQ inhibited viability, proliferation, and invasion, and induced apoptosis of SKOV3 and OVCAR3 cells through the PI3K/Akt/mTOR pathway. Together, the data revealed that ILQ treatment may be used as a novel strategy for ovarian cancer therapy. Keywords: isoliquiritigenin (ILQ), ovarian cancer, SKOV3, OVCAR3, apoptosis, PI3K/Akt/mTOR pathway

Shi-Yang Xie, Guang Li, Chong Han, Yang-Yang Yu, Nan Li Department of Radiation Oncology, The First Affiliated Hospital of China Medical University, Shenyang, China Abstract: Non-small-cell lung cancer (NSCLC) is exceptionally deadly because the tumors lack sensitive early-stage diagnostic biomarkers and are resistant to radiation and chemotherapy. Here, we investigated the role and mechanism of Raf kinase inhibitory protein (RKIP) in NSCLC radioresistance. The clinical data showed that the RKIP expression level was generally lower in radioresistant NSCLC tissues than in radiosensitive tissues. Reduced RKIP expression was related to NSCLC radioresistance and poor prognosis. In vitro experiments showed that RKIP knockdown increased radioresistance and metastatic ability in NSCLC cell lines. Mechanistically, RKIP reduction activated the Shh signaling pathway by derepressing Smoothened (Smo) and initiating glioma-associated oncogene-1 (Gli1)-mediated transcription in NSCLC. In addition, the inappropriately activated Shh–Gli1 signaling pathway then enhanced cancer stem cell (CSC) expression in the cell lines. The increasing quantity of CSCs in the tumor ultimately promotes the radiation resistance of NSCLC. Together, these results suggest that RKIP plays a vital role in radiation response and metastasis in NSCLC. RKIP reduction enhances radioresistance by activating the Shh signaling pathway and initiating functional CSCs. This role makes it a promising therapeutic target for improving the efficacy of NSCLC radiation treatment.Keywords: RKIP, radiosensitivity, Shh signaling pathway, CSCs, NSCLC&nbsp

Jianyang Wang, Yuan Tian, Yuan Tangm, Xin Wang, Ning Li, Hua Ren, Hui Fang, Yanru Feng, Shulian Wang, Yongwen Song, Yueping Liu, Weihu Wang, Yexiong Li, Jing Jin Department of Radiation Oncology, National Cancer Center/Cancer Hospital, Chinese Academy of MedicalSciences & Peking Union Medical College, Beijing, People’s Republic ofChina Purpose: This study aimed to spare hematopoietical bone marrow (BM) identified by magnetic resonance (MR) radiation in order to alleviate acute hematologic toxicity (HT) for gastric cancer patients treated with postoperative chemoradiotherapy (CRT).Methods: A prospective, open-label, single-arm Phase II study (Clinicaltrials.gov; NCT 01863420) was conducted in 25 patients with gastric cancer who were eligible for postoperative concurrent CRT. The MR images of vertebral body T8-L4 were fused with images of simulating computed tomography. Hematopoietical BM was contoured according to the MR and spared in radiotherapy plan. The CRT regimen consisted of daily capecitabine (1600mg/m2/d) and 45 Gy of radiation at 1.8 Gy per day. Primary endpoints were grade ≥3 HT that occurred within 2 months of initiation of CRT. The relationship between HT and dose–volume of BM was estimated by multivariable linear regression model.Results: Twenty four patients (96%) had T3–4 disease and 22 (88%) had disease with node positive. The median age was 53 years (range, 28–73 years). Before concurrent CRT, adjuvant chemotherapy was administered with a mean cycle of 4.3±0.5. Only five patients (20%) developed grade 3–4 HT during treatment, among whom two (8.0%) patients experienced grade 3–4 leucopenia, two (8.0%) experienced neutropenia, and two (8.0%) experienced thrombocytopenia, respectively. None of the patients showed grade 3–4 anemia. Multivariable linear regression revealed increased BM-V5 (P=0.03) and BM-V20 (P=0.002) were found to be significantly associated with decreased white blood cells nadirs in multivariable regression; increased BM-V20 (P

Xinxin He, Yangnian Wei, Yong Wang, Ling Liu, Wen Wang, Nianfeng Li Department of Hepatobiliary and PancreaticSurgery, XiangyaHospital, Central South University, Hunan, People’s Republic of China Abstract: MiR-381 has been reported to be dysregulated in several human cancers. However, the function and mechanism of miR-381 in colorectal cancer (CRC) remains unclear. In the present study, the miR-381 expression was assessed in a cohort of 113 CRC specimens using real-time quantitative polymerase chain reaction (RTq-PCR), which demonstrated that miR-381 was significantly downregulated in CRC and correlated with distant metastasis and tumor, node, and metastasis (TNM) stage. Functional study revealed that restoration of miR-381 significantly inhibited the invasion, migration, and epithelial–mesenchymal transition (EMT) of CRC cells. Luciferase reporter assay validated that Twist1, an important EMT inducer, was a direct target of miR-381, and rescued Twist1 attenuated the function of miR-381 in CRC cells. Correlation analysis also revealed an inverse correlation between miR-381 and Twist1 expression levels in CRC specimens. Taken together, our results highlight the significance of miR-381/Twist1 interaction in the development and progression of CRC, and suggest that restoration of miR-381 may be a potential therapeutic strategy for the patients with CRC. Keywords: colorectal cancer, miR-381, twist family bHLH transcription factor 1, Twist1, epithelial–mesenchymal transition,EMT

Wei Zhou,1,2 Liuqun Jia,3 Shujin Guo,3 Qianjin Hu,3 Yongchun Shen,3 Ningxiu Li1 1West China School of Public Health, Sichuan University, 2Human Body Function Laboratory, Chengdu University of Technology, Chengdu, 3Division of Pulmonary Diseases, State Key Laboratory of Biotherapy of China and Department of Respiratory Medicine, West China Hospital of Sichuan University, Chengdu, People's Republic of China Purpose: The -159C/T polymorphism in the cluster of differentiation (CD)14 gene has been extensively studied for an association with cancer; however, results from replication studies have been inconclusive. The aim of this study was to perform a comprehensive assessment of the possible association between the -159C/T polymorphism in the CD14 gene and cancer risk, by meta-analysis. Methods: We searched in PubMed, Embase, and other databases, covering all case-control studies on the possible association between CD14 -159C/T gene polymorphism and cancer risk. Data were extracted and statistical analyses were performed using RevMan 5.0 and STATA 12.0 software. Results: A total of 12 case-control studies met our inclusion criteria, including 2,498 cases and 2,696 controls. The combined analysis indicated that the CD14 -159C/T gene polymorphism didn't confer risk for cancer - the recessive model (TT versus (vs) CT + CC), showed odds ratio (OR) =1.01, 95% confidence interval (CI) =0.82–1.23 (P=0.94), while the dominant model (TT + TC vs CC) showed OR =0.81, 95% CI =0.66–1.00 (P=0.05). A subgroup analysis by ethnicity showed that the cancer risk associated with CD14 -159C/T gene polymorphism was significantly decreased among Caucasians for the TC + TT vs CC comparison (OR =0.83, 95% CI =0.70–0.98 [P=0.03]). The subgroup analysis by cancer type suggested that the CD14 -159C/T gene polymorphism was not associated with gastric cancer risk. Conclusion: The evidence from the present meta-analysis did not support the CD14 -159C/T gene polymorphism as a genetic risk factor for cancer. Further studies on different cancer types and ethnicities are needed to validate our findings. Keywords: CD14, cancer, gene, polymorphism, meta-analysis