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Su-ping Guo,1,2,* Chen Chen,1,2,* Zhi-fan Zeng,1,2 Qiao-xuan Wang,1,2 Wu Jiang,2,3 Yuan-hong Gao,1,2 Hui Chang1,2 1Department of Radiation Oncology, Sun Yat-sen University Cancer Center, Guangzhou, People’s Republic of China; 2State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, People’s Republic of China; 3Department of Colorectal Surgery, Sun Yat-sen University Cancer Center, Guangzhou, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yuan-hong Gao; Hui ChangDepartment of Radiation Oncology, Sun Yat-sen University Cancer Center, 651 Dongfeng Road East, Guangzhou, Guangdong, 510060, People’s Republic of ChinaTel +86-13560182168; +86-13480295989Email gaoyh@sysucc.org.cn; changhui@sysucc.org.cnBackground: Serum lipids have been reported as prognosticators for malignancies, including rectal cancer (RC). Yet, their value in predicting the response of RC to neoadjuvant chemoradiotherapy (NACRT) remains unknown. This study aimed to assess the predictive abilities of serum lipids for a bad response, and to build a serum lipid-based prediction model.Methods: In total, 751 patients diagnosed with stage cII–III RC and treated with NACRT plus surgery from January 2007 to August 2018 were retrospectively reviewed and randomly divided into two data sets, in a ratio of 1:1. Receiver operating characteristics (ROC) analysis was conducted in the development set to select possible predictors of bad NACRT response from pathoclinical factors, including serum lipids. Multivariate logistic regression was conducted to further determine independent predictors, which were then used to develop a prediction index (PI). Finally, the PI was verified in the validation set, through ROC analysis and chi-squared test.Results: Five independent predictors were identified: tumor length ≥ 4 cm, cT4 stage, carcinoembryonic antigen ≥ 5.0 ng/mL, irradiation with three-dimensional conformal radiotherapy technique, and apolipoprotein A-I ≤ 1.20 g/L. Each of them was assigned a number of points. In the validation set, the area under the curve of PI appeared as 0.642 (95% confidence interval 0.586– 0.697). The sensitivity, specificity, positive and negative predictive values, and concordance were 72.3%, 52.3%, 63.8%, 61.9%, and 63.0%, respectively.Conclusion: Serum apolipoprotein A-I was found to correlate negatively with the RC response to NACRT. It could serve as a biomarker for guiding individualized treatment and a potential target for improving sensitivity to chemoradiation.Keywords: rectal cancer, radiotherapy, apolipoprotein A-I, tumor response, prediction model

Cuiyun Su,1,* Maojian Chen,1,* Guanxuan Chen,2,* Yajun Li,3 Ning Li,4 Zhihuang Hu,5 Xiao Hu,6,7 Yuanyuan Zhao,8– 10 Qitao Yu,1 Wei Jiang1 1Department of Respiratory Oncology, Guangxi Medical University Cancer Hospital, Nanning, Guangxi, 530021, People’s Republic of China; 2Department of Intensive Care Unit, Shandong Cancer Hospital Affiliated to Shandong University, Jinan, Shandong, 250117, People’s Republic of China; 3Department of Lymphoma and Hematology, Hunan Cancer Hospital & the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan, 410013, People’s Republic of China; 4Department of Oncology, Henan Cancer Hospital & the Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, Henan, 450008, People’s Republic of China; 5Department of Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai, 200032, People’s Republic of China; 6Department of Radiation Oncology, Cancer Hospital of the University of Chinese Academy of Sciences & Zhejiang Cancer Hospital, Hangzhou, Zhejiang, 310022, People’s Republic of China; 7Department of Radiation Oncology, Institute of Cancer Research and Basic Medical Sciences, Chinese Academy of Sciences, Hangzhou, Zhejiang, 310022, People’s Republic of China; 8Department of Medical Oncology, Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong, 510060, People’s Republic of China; 9State Key Laboratory of Oncology in South China, Guangzhou, Guangdong, 510060, People’s Republic of China; 10Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong, 510060, People’s Republic of China*These authors contributed equally to this workCorrespondence: Wei Jiang; Qitao Yu Department of Respiratory OncologyGuangxi Medical University Cancer Hospital, No. 71, Hedi Road, Qingxiu District, Nanning, Guangxi, 530021, People’s Republic of ChinaTel/Fax +86 0771 5334953Email jiangweiac@hotmail.com; yuqitaoac@126.comBackground: Inadequate control of cancer-related pain in China is an ongoing problem. This study investigated the practices of cancer pain (CP) management at major cancer centers in China and perceived hindrances and knowledge of CP management among health professionals.Methods: From September to October 2019, a survey was conducted using electronic questionnaires via the internet to investigate the practices, and perceived hindrances and knowledge in managing CP among healthcare professionals from 7 provincial cancer centers in China. The questionnaire included demographic data, the professionals’ practices among their own patients, their opinions regarding hindrances to CP management, and knowledge of CP management.Results: We gathered validated responses from 411 anonymous healthcare professionals, with 82.2% (411/500) of response rate. Based on the analysis of these 411 questionnaires, the results demonstrated that CP was prevalent among patients with cancer, while moderate-to-severe pain took a great proportion. CP management was inadequate for a significant proportion of the patients with CP. Pain assessment, analgesic treatment, attention to adverse effects of analgesic, and multidisciplinary management were usually ineffectual in many cases. The duration of work experience did not significantly affect CP management. The respondents considered that both patients and healthcare professionals were responsible for the undermanagement of CP. Only 26 (6.3%) respondents were able to answer correctly all 10 of the professional questions regarding CP.Conclusion: CP is commonly undermanaged in China. Effective pain control requires the implementation of standards, and the sufficient attention and training of healthcare professionals.Keywords: cancer pain, pain control, pain treatment, quality of life, electronic questionnaire

Xueling Ge,1 Wei Jiang,2 Yujie Jiang,1 Xiao Lv,1 Xin Liu,1 Xin Wang1 1Department of Hematology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong 250021, People’s Republic of China; 2Information Center, Shandong Mental Health Center, Jinan, Shandong 250014, People’s Republic of ChinaCorrespondence: Xin WangDepartment of Hematology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong 250021, People’s Republic of ChinaTel +86-13156012606Fax +86-531-87068707Email xinw007@126.comObjective:: TMED2 is a member of the transmembrane emp24 domain (Tmed)/p24 protein family, which is significantly upregulated in breast cancer, ovarian cancer and other tumour tissues. The purpose of this study was to investigate the expression of TMED2 in MM cell lines and its effect on the biological behaviour of MM cell lines.Methods: Real-time quantitative PCR (RT-qPCR) was used to detect the expression of TMED2 in MM cell lines, including MM.1S and RPMI 8226 cells, and lentivirus vector-mediated TMED2 gene silencing was used to further study the effect of the downregulation of TMED2 expression on cell viability, the cell cycle, and apoptosis.Results: Based on the RT-qPCR results, the expression of the TMED2 mRNA was increased in the MM cell lines MM.1S and RPMI 8226 compared with endogenous control GAPDH. The expression of the TMED2 mRNA was substantially reduced after transfection of the shRNA targeting TMED2 (shTMED2) in both MM cell lines. The CCK-8 assay showed significant decreases in the viability of MM.1S and RPMI 8226 cells, suggesting that the TMED2 gene plays an important role in the proliferation of these two cell lines. The cell cycle of MM.1S and RPMI 8226 cells was substantially altered by shTMED2, as evidenced by the increased number of cells in G1 phase and decreased number of cells in S and G2/M phases. The FACS analysis revealed a significant increase in the apoptosis of MM.1S and RPMI 8226 cells due to the increased activity of Caspase 3/7, suggesting that the TMED2 gene is significantly related to the apoptosis of these two cell lines.Conclusion: Based on these results, TMED2 may play an important role in the pathogenesis of MM. This novel study may contribute to further investigations of useful biomarkers and potential therapeutic targets in patients with MM.Keywords: multiple myeloma, TMED2, FACS, shRNA

Yaqi Xu,1– 3 Xiaoli Feng,4 Qian Zhou,1,2,5 Wen Jiang,1,2,6 Yibo Dai,1– 3 Yang Jiang,1– 3 Xiaoli Liu,1– 3 Shuo Li,1,2,7 Yongjing Wang,1– 3 Fang Wang,6 Ai Li,1– 3 Chengyun Zheng1– 3 1Department of Hematology, The Second Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, People’s Republic of China; 2Institute of Biotherapy for Hematological Malignancies, Shandong University, Jinan, Shandong, People’s Republic of China; 3Shandong University-Karolinska Institute Collaboration Laboratory for Stem Cell Research, Jinan, Shandong, People’s Republic of China; 4Clinical Laboratory, The Second Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, People’s Republic of China; 5Department of Hematology, Linyi Central Hospital, Linyi, Shandong, People’s Republic of China; 6Institute of Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, People’s Republic of China; 7Binzhou Medical University Hospital, Binzhou, Shandong, People’s Republic of ChinaCorrespondence: Chengyun Zheng; Ai LiHematology Department of the Second Hospital of Shandong University, 247th of Beiyuan Road, Jinan, Shandong, People’s Republic of ChinaTel +86 13675319282; +86 176 6008 0688Email zhengchengyun186@126.com; aili1976@126.comBackground: We aimed to investigate the anti-multiple myeloma (MM) activity of the new small molecular compound AE-848 (5-bromo-2-hydroxyisophthalaldehyde bis[(1-methyl-1H-benzimidazol-2-yl)hydrazone]) and its underlying anti-MM mechanism.Methods: Cell viability and apoptosis were detected and quantified by using MTT and flow cytometry, respectively. JC-1 dye-related techniques were used to assess mitochondrial membrane potential (MMP). Western blotting was applied to detect the expression of NF-κB and PI3K/Akt/mTOR pathway-associated proteins. The in vivo activity of AE-848 against MM was evaluated in a MM mouse model.Results: Application of AE-848 into the in vitro cell culture system significantly reduced the viability and induced apoptosis of the MM cell lines, RPMI-8226 and U266, in a dose- and time-dependent manner, respectively. JC-1 dye and Western blotting analysis revealed that AE-848 induced the cleavage of caspase-8, caspase-3, and poly ADP-ribose polymerase (PARP), resulting in loss of mitochondrial membrane potential (MMP). Both the NF-κB and PI3K/AKT/mTOR signaling pathways were involved in AE-848-induced apoptosis of U266 and RPMI8226 cells. Moreover, AE-848 leads to cell cycle arrest of MM cells. Its anti-MM efficacy was further confirmed in a xenograft model of MM. AE-848 administration significantly inhibited MM tumor progression and prolonged the survival of MM-bearing mice. More importantly, our results demonstrated that AE-848 markedly induced primary MM cell apoptosis.Conclusion: Our results for the first time showed that the small compound AE-848 had potent in vitro and in vivo anti-myeloma activity, indicating that AE-848 may have great potential to be developed as a drug for MM treatment.Keywords: small molecular compound, AE-848, multiple myeloma, apoptosis, NF-κB and PI3K/Akt/mTOR pathway

Cuiyun Su,1 Ya Jiang,2 Wei Jiang,1 Huilin Wang,1 Sisi Liu,2 Yang Shao,2 Wenhua Zhao,1 Ruiling Ning,1 Qitao Yu1 1Department of Respiratory Oncology, Guangxi Medical University Affiliated Tumor Hospital, Nanning, China; 2Department of Research and Development, Nanjing Geneseeq Technology Inc, Nanjing, Jiangsu, ChinaCorrespondence: Qitao Yu Email yqt133@126.comAbstract: Non-small cell lung cancer (NSCLC) patients with anaplastic lymphoma kinase (ALK) rearrangement benefit from treatment with ALK inhibitors. Therefore, the identification of druggable ALK fusions is necessary for NSCLC treatment. More than 90 fusion partners of ALK have been reported in NSCLC patients, but the striatin gene (STRN)-ALK fusion has rarely been reported. Moreover, the response of STRN-ALK fusion patients treated with ALK inhibitors remains to be explored. A 64-year-old Chinese male with no history of smoking or alcohol consumption was diagnosed as stage IVB lung adenocarcinoma (LADC) (cT4N3M1c) in October 2018. Next-generation sequencing (NGS) targeting 425 cancer-related genes was performed on the plasma and supernatant of pleural effusion samples and revealed an STRN-ALK fusion. The patient received alectinib (600 mg, twice daily) as the first-line treatment with an excellent response exceeding 19 months. This is the first report of a NSCLC patient harboring an STRN-ALK fusion and exhibiting an excellent response to alectinib treatment. This case provides valuable information for therapeutic decision-making of patients with STRN-ALK fusions. Furthermore, this case also highlighted the advantage of performing targeted NGS on circulating tumor DNA for the identification and analysis of rare, druggable genomic alterations.Keywords: lung adenocarcinoma, STRN-ALK fusion, ctDNA, alectinib, targeted NGS

Wenxiu Jiang,1,* Lili Wang,2,* Yajuan Zhang,1 Hongliang Li1 1Department of Infectious Diseases, The People’s Hospital of Danyang, Affiliated Danyang Hospital of Nantong University, Danyang City, Jiangsu Province, People’s Republic of China; 2Department of Clinical Research, The Second Hospital of Nanjing, Nanjing University of Chinese Medicine, Nanjing City, Jiangsu Province, People’s Republic of China*These authors contributed equally to this workCorrespondence: Hongliang LiDepartment of Infectious Diseases, The People’s Hospital of Danyang, Affiliated Danyang Hospital of Nantong University, No. 2 Xinmin West Road, Danyang 212300, Jiangsu Province, People’s Republic of ChinaTel/Fax +86 511-86553015Email chiwdu@163.comBackground: Circular RNAs (circRNAs) play an important regulatory role in various cancers, including hepatocellular carcinoma (HCC). This study aimed to investigate the function of hsa_circ_0006942 (circ-ATP5H) in hepatitis B virus (HBV)-associated HCC and its underlying mechanism.Methods: The levels of circ-ATP5H, miR-138-5p and tumor necrosis factor alpha-induced protein 3 (TNFAIP3) were determined using quantitative real-time polymerase chain reaction (qRT-PCR) or Western blot assay. The copies of HBV DNA were examined using qRT-PCR. The levels of hepatitis B surface antigen (HBsAg) and hepatitis B e antigen (HBeAg) were detected via enzyme-linked immunosorbent assay (ELISA). Dual-luciferase reporter assay was used to analyze the interactions among circ-ATP5H, miR-138-5p and TNFAIP3.Results: Circ-ATP5H and TNFAIP3 levels were increased, while miR-138-5p level was reduced in HBV-positive HCC tissues and cells. Knockdown of circ-ATP5H hindered HBV DNA replication and decreased HBsAg and HBeAg levels in HBV-infected cells. Circ-ATP5H silencing suppressed HBV replication and expression by regulating miR-138-5p. Moreover, miR-138-5p blocked HBV replication and expression via targeting TNFAIP3. Furthermore, circ-ATP5H up-regulated TNFAIP3 via absorbing miR-138-5p.Conclusion: Circ-ATP5H promoted HBV replication and expression through modulating miR-138-5p/TNFAIP3 axis, suggesting a new biomarker for HBV-related HCC treatment.Keywords: hepatitis B virus, hepatocellular carcinoma, circ-ATP5H, miR-138-5p, TNFAIP3

Xiangpeng Kang,1 Hongzhe Shi,1 Dong Wang,1 Zejun Xiao,1 Jun Tian,1 Xingang Bi,1 Weixing Jiang,1 Changling Li,1 Jianhui Ma,1 Shan Zheng,2 Yueping Sun,3 Jianzhong Shou1 1Department of Urinary Surgery, National Cancer Center, National Clinical Research Center for Cancer, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, People’s Republic of China; 2Department of Pathology, National Cancer Center, National Clinical Research Center for Cancer, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, People’s Republic of China; 3Institute of Medical Information, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100020, People’s Republic of ChinaCorrespondence: Yueping Sun Email sun.yueping@imicams.ac.cnJianzhong Shou Email shoujzh@126.comPurpose: This study aimed to construct a predictive model for recurrence and metastasis in patients with localized clear cell renal cell carcinoma (ccRCC) based on multiple preoperative blood indexes and oncological characteristics.Patients and Methods: Overall, 442 patients with localized ccRCC between 2013 and 2015 were included. Using least absolute shrinkage and selection operator (LASSO) Cox regression analysis, the top three risk factors from the peripheral blood indicators were screened to construct a risk score, and a prognostic model was established. Harrell’s concordance index (C-index) was applied to evaluate the predictive accuracy of the model for predicting disease-free survival (DFS) in ccRCC.Results: Out of 38 blood indexes, the top three predictors were fibrinogen (FIB), C-reactive protein (CRP) and neutrophil-lymphocyte ratio (NLR). The FIB-CRP-NLR (FCN) score (hazard ratio [HR]: 1.86, 95% confidence interval [CI]: 1.21– 2.9, P = 0.005) was an independent prognostic factor in multivariate analysis. Furthermore, the FIB-CRP-NLR-T-Grade (FCNTG) risk model combining FCN score, T stage and Furhman grade achieved a higher prognostic accuracy (mean C-index, 0.728) than both the FCN score alone (mean C-index, 0.675) and the stage, size, grade, and necrosis (SSIGN) score (mean C-index, 0.686) in the validation cohort.Conclusion: The FCN score combining peripheral blood indicators of inflammation and coagulation is an independent prognostic marker of ccRCC. The FCNTG model, which systemically incorporates preoperative blood indexes to oncological characteristics, shows its advantages of convenience and high prediction efficiency.Keywords: clear cell renal cell carcinoma, prognosis, fibrinogen, C-reactive protein, neutrophil-lymphocyte ratio

Maojian Chen,1,* Wei Jiang,2,* Chanchan Xiao,3 Weiping Yang,4 Qinghong Qin,1 Anyun Mao,1 Qixing Tan,1 Bin Lian,1 Changyuan Wei1 1Department of Breast Surgery, Guangxi Medical University Cancer Hospital, Nanning, Guangxi 530021, People’s Republic of China; 2Department of Medical Oncology, Guangxi Medical University Cancer Hospital, Nanning, Guangxi 530021, People’s Republic of China; 3Department of Microbiology and Immunology, School of Medicine, Jinan University, Guangzhou, Guangdong 510632, People’s Republic of China; 4Department of Ultrasound Diagnosis, Guangxi Medical University Cancer Hospital, Nanning, Guangxi 530021, People’s Republic of China*These authors contributed equally to this workCorrespondence: Changyuan Wei Department of Breast SurgeryGuangxi Medical University Cancer Hospital, Nanning, Guangxi 530021, People’s Republic of ChinaTel/Fax +86 771 5308593Email changyuanwei@gxmu.edu.cnPurpose: This study is aimed to investigate the combined treating efficacy of sodium butyrate and docetaxel on proliferation and apoptosis of the lung adenocarcinoma A549 cell line based on Gli1 regulation in vitro and in vivo.Materials and Methods: RNA interference method was used to overexpress Gli1 in A549 cells. Cells were treated with varying concentrations of sodium butyrate, docetaxel or both in combination. CCK-8, colony formation assay, Hoechst 33258 staining, flow cytometry and TUNEL assay were employed to detect proliferation, cell cycle and apoptosis. qRT-PCR and Western blot analysis were applied to detect the mRNA and protein expression of Gli1. In vivo tumorigenicity was detected by tumor transplantation in nude mice. Downstream protein levels of Gli1 were detected using Western blot assay.Results: It was found that sodium butyrate or docetaxel alone, respectively, inhibited proliferation and promoted apoptosis of A549 cells in vitro and in vivo, while the combination of the two generated significantly higher responses, which were also effective in another lung adenocarcinoma cell line H1299. Furthermore, the combined therapy had an additive effect in suppressing Gli1 expression and regulating the expression of its downstream proteins that involve in proliferation, cell cycle and apoptosis of A549 cells in vitro and in vivo, including decreased protein expression of Ki-67, CDK1, CDK2, Cyclin D1, Bcl-2 and Survivin, and increased protein expression of Cyclin A, p21, Bax and cleaved-Caspase 3. On the other hand, Gli1 overexpression perceptibly reversed the above-mentioned additive effect in vitro and in vivo.Conclusion: This study demonstrates that the combined therapy of sodium butyrate and docetaxel additively inhibits proliferation and promotes apoptosis of A549 lung adenocarcinoma cells via suppressing Gli1 expression in vitro and in vivo. Targeting Gli1 by the combined therapy may provide new insights into the therapeutic management of patients with lung adenocarcinoma.Keywords: sodium butyrate, docetaxel, lung adenocarcinoma, A549, Gli1

Hongzhong Cheng1 ,* Wen Jiang1 ,* Zhengji Song,2 Ting Li,2 Yulian Li,2 Libin Zhang,1 Guoping Wang1 1Department of Thoracic Surgery, The First People’s Hospital of Yunnan Province, Kunming, Yunnan, People’s Republic of China; 2Department of Gastroenterology, The First People’s Hospital of Yunnan Province, Kunming, Yunnan, People’s Republic of China*These authors contributed equally to this workCorrespondence: Guoping WangDepartment of Thoracic Surgery, The First People’s Hospital of Yunnan Province, Kunming City, Yunnan Province, People’s Republic of ChinaTel +86-871-63638675Email cxdlib@163.comBackground: Circular RNAs (circRNAs) are critical regulators of many diseases, including esophageal squamous cell carcinoma (ESCC). A recent study has shown that circLPAR3 is highly expressed in ESCC, but its role and mechanism in ESCC are still unclear.Methods: The expression levels of circLPAR3, microRNA-375 (miR-375), miR-433, and high-mobility group box 1 (HMGB1) were measured by quantitative real-time polymerase chain reaction (qRT-PCR). The circular characteristic and localization of circLPAR3 were identified by Ribonuclease R (RNase R) and nuclear-cytoplasmic separation assay. Also, cell proliferation was detected by cell counting kit-8 (CCK-8) and colony formation assays. Cell migration and invasion were tested by transwell assay. Moreover, Western blot (WB) analysis was used to test the levels of proliferation and metastasis-related protein, as well as the HMGB1 protein. Besides, mice xenograft models were constructed to assess the effect of circLPAR3 on ESCC tumor growth in vivo. In addition, dual-luciferase reporter and RNA pull-down assays were used to identify the mechanism of circLPAR3.Results: CircLPAR3 was upregulated in ESCC tissues and cells, and its high expression was related to the poor prognosis of ESCC patients. CircLPAR3 was a stable cyclic transcript, mainly located in the cytoplasm, and its knockdown hindered the proliferation, migration and invasion of ESCC cells and inhibited ESCC tumor growth in vivo. MiR-375/miR-433 could be sponged by circLPAR3, and their inhibitors could reverse the suppression effect of silenced circLPAR3 on ESCC progression. HMGB1 could be targeted by miR-375/miR-433, and its overexpression also could invert the inhibition effect of circLPAR3 knockdown on ESCC progression.Conclusion: CircLPAR3 might play an oncogenic role in ESCC through sponging miR-375/miR-433 to promote HMGB1 expression, which might provide a theoretical basis for circLPAR3 to become a biomarker for ESCC therapy.Keywords: ESCC, circLPAR3, miR-375, miR-433, HMGB1

Liang Zeng,1,2,* Yizhi Li,2,* Qinqin Xu,3,* Wenjuan Jiang,2 Analyn Lizaso,4 Xinru Mao,4 Yongchang Zhang,2 Nong Yang,2 Zhenxing Wang1 1Department of Medical Oncology, The First Affiliated Hospital of Soochow University, Suzhou 215006, People’s Republic of China; 2Department of Medical Oncology, Lung Cancer and Gastrointestinal Unit, Hunan Cancer Hospital/The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha 410013, People’s Republic of China; 3Department of Medical Oncology, Qinghai Provincial People’s Hospital, Xining, People’s Republic of China; 4Department of Medical Affairs, Burning Rock Biotech, Guangzhou, 510300, People’s Republic of China*These authors contributed equally to this workCorrespondence: Nong YangDepartment of Medical Oncology,Lung Cancer and Gastrointestinal Unit, Hunan Cancer Hospital/The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha 410013, People’s Republic of ChinaTel +86 73189762327Email yangnong0217@163.cnZhenxing WangDepartment of Medical Oncology, The First Affiliated Hospital of Soochow University, 188 Shizi Street, Suzhou 215006, People’s Republic of ChinaTel +86 73189762327Email zhenxw316@163.comIntroduction: Reliable diagnostic approaches to detect ALK rearrangement are critical for selecting patients eligible for crizotinib therapy. This study aimed to compare next-generation sequencing (NGS) and Ventana immunohistochemistry (IHC) in evaluating ALK rearrangements and evaluate their impact on first-line crizotinib efficacy.Patients and Methods: A total of 472 NSCLC patients were identified as ALK-positive by NGS and/or IHC between March 2014 and February 2020. The concordance of ALK detection, overall response rate (ORR), and progression-free survival (PFS) were analyzed for 319 patients who received front-line crizotinib.Results: First-line crizotinib (n=319) significantly prolonged PFS in comparison with chemotherapy (n=46; 12.0 vs 6.8 months; p< 0.0001). Of the 76 crizotinib-treated patients whose ALK status was assessed by both NGS and IHC, 78.9% of the patients had concordant ALK status (NGS-positive/IHC-positive), 18.4% patients were NGS-positive but IHC-negative, and 2 patients were IHC-positive but NGS-negative. Different detection assays confer no statistical difference in ORR and PFS with first-line crizotinib. The ORR in NGS only, IHC only, and both NGS and IHC was 84.3%, 90.1%, and 88.1%, respectively, while PFS was 11.4, 13.0, and 11.0 months, respectively. The ORR in NGS-positive/IHC-positive and NGS-positive/IHC-negative patients was 85.4% and 92.8%, respectively. Compared to NGS-positive/IHC-positive patients, those with NGS-positive/IHC-negative results had a trend of shorter PFS but statistical significance was not reached (mPFS, 5.9 months vs 11.5 months, p=0.43).Conclusion: Our results demonstrate that ALK status detected by NGS and/or IHC is reliable in identifying patients with ALK-positive NSCLC who will benefit from ALK inhibitor therapy.Keywords: ALK status evaluation, ALK IHC, ALK inhibitor

Ruonan Jiao,* Si Zhao,* Wei Jiang, Xin Wei, Guangming Huang Medical Center for Digestive Diseases, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Guangming Huang Email hgmnjmu@hotmail.comBackground: Gastrointestinal stromal tumours (GISTs) are the most common mesenchymal neoplasms. Endoscopic submucosal dissection (ESD) has been used to remove submucosal tumours for many years. However, whether ESD can be recommended for the treatment of GISTs is still controversial. Therefore, we evaluated the efficacy and safety of ESD for treating GISTs.Patients and Methods: We retrospectively analysed 75 GIST patients who underwent ESD in our hospital from January 2016 to December 2018, and the demographic data, clinical presentation of tumours, operative parameters, postoperative complications and length of hospital stay were analysed.Results: Seventy-five patients successfully underwent en bloc resection, and 74 (98.7%) patients underwent complete resection of the lesions, with an average tumour size of 1.7 cm (range 0.3– 6.0 cm). The median operation time was 84.8 min (range 20– 180 min). Forty-two (56.0%) patients underwent endoscopic purse-string suture with no conversions to an open operation. The median postoperative length of hospitalization was 6.6 days (range 3– 14 days). Out of a total of 75 GIST patients, 48 (64.0%) were considered very low risk, 19 (25.3%) were low risk, 5 (6.7%) were mild risk, and 3 (4.0%) were high risk. The median follow-up was 24.0 months (range 6– 45 months). During hospitalization and follow-up, no complications, recurrence or metastasis occurred.Conclusion: Based on our study from a medical centre, ESD is a safe and effective method for treating GISTs. However, further studies are needed.Keywords: endoscopic submucosal dissection, gastrointestinal stromal tumour, prognosis &nbsp

Wei Jiang,1 Xiaofei Deng,1 Ting Zhu,1 Yuya Wei,1 Zhen Lei,1 Meimei Guo,2 Jiong Yang2 1Department of Ultrasound, Huazhong University of Science and Technology Union Shenzhen Hospital, Shenzhen 518052, People’s Republic of China; 2Department of Gastroenterology, Huazhong University of Science and Technology Union Shenzhen Hospital, Shenzhen 518052, People’s Republic of ChinaCorrespondence: Wei JiangDepartment of Ultrasound, Shenzhen Nanshan District People’s Hospital, No. 89, Taoyuan Road, Nanshan District, Shenzhen 518052, People’s Republic of ChinaTel +86 13026628099Email jwszdr@126.comBackground: Identification of cholangiocarcinoma (CCA) associated with hepatolithiasis (HL) is difficult. There is no effective method to discriminate CCA associated with HL (HL-CCA) from HL currently.Objective: To explore the value of clinical data, ultrasonic characteristics and miRNA expression level in the identification of HL-CCA.Methods: Thirty-one patients with HL-CCA in Huazhong University of Science and Technology Union Shenzhen Hospital were enrolled in the observation group, while 40 patients with HL alone were included in the control group. The clinical data, ultrasonic characteristics, and miRNA expression level of the two groups were recorded and analyzed to explore the potential indicators for the identification of HL-CCA.Results: The accuracy of ultrasound in the diagnosis of HL-CCA was low (54.84%). Multivariate logistic regression analysis showed that liver abscess (P=0.021), indistinct border demarcation (P=0.015), non-homogenous echotexture (P=0.019), missed portal vein around lesion (P=0.032), miRNA-21 (P=0.018) and miRNA-221 (P=0.009) were the potential indicators for the identification of HL-CCA. The combined diagnosis based on logistic regression contained liver abscess, border demarcation, echotexture, portal vein around lesion, miRNA-21 and miRNA-221. The results showed that the accuracy of combined diagnosis identifying HL-CCA was the most accurate (AUC=0.911), which was significantly greater than the AUC of miRNA-21 or miRNA-221 individually (P< 0.05), with a sensitivity and specificity of 77.42% and 97.50%, respectively.Conclusion: Patients with HL-CCA show high incidence of hepatic abscess and elevated miRNA-21 and miRNA-221 expression level. The ultrasonic features are more likely to show indistinct border demarcation, non-homogenous echotexture, and missed portal vein around lesion. The combined diagnosis is more accurate in the identification of HL-CCA.Keywords: cholangiocarcinoma, hepatolithiasis, microRNA, differential diagnosis, combined diagnosis, ultrasound

Yichi Xu, Wenxiao Jiang, Shangdan Xie, Fang Xue, Xueqiong Zhu Department of Obstetrics and Gynecology, The Second Affiliated Hospital of Wenzhou Medical University, Wenzhou, People’s Republic of ChinaCorrespondence: Xueqiong ZhuDepartment of Obstetrics and Gynecology, The Second Affiliated Hospital of Wenzhou Medical University, No. 109 Xueyuan Xi Road, Wenzhou, Zhejiang 325027, People’s Republic of ChinaTel/Fax +86 577 88002796Email zjwzzxq@163.comAbstract: Inhaled anesthetics are widely used for induction and maintenance of anesthesia during surgery, including isoflurane, sevoflurane, desflurane, haloflurane, nitrous oxide (N2O), enflurane and xenon. Nowadays, it is controversial whether inhaled anesthetics may influence the tumor progression, which urges us to describe the roles of different inhaled anesthetics in human cancers. In the review, the relationships among the diverse inhaled anesthetics and patient outcomes, immune response and cancer cell biology were discussed. Moreover, the mechanisms of various inhaled anesthetics in the promotion or inhibition of carcinogenesis were also reviewed. In summary, we concluded that several inhaled anesthetics have different immune functions, clinical outcomes and cancer cell biology, which could contribute to opening new avenues for selecting suitable inhaled anesthetics in cancer surgery.Keywords: inhaled anesthetics, cancer, tumorigenesis, surgery, immune

Reem N Hassan,* Hualei Luo,* Weiying Jiang Department of Medical Genetics, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, Guangdong 510080, People’s Republic of China*These authors contributed equally to this workCorrespondence: Weiying JiangDepartment of Medical Genetics, Zhongshan School of Medicine, Sun Yat-Sen University, No. 74, Zhongshan Second Road, Yuexiu District, Guangzhou, Guangdong 510080, People’s Republic of ChinaTel +86-20-87331928Email jiangwy@mail.sysu.edu.cnPurpose: The present study aimed to examine the effects of nicotinamide (NAM) on cervical cancer-associated fibroblasts (CAF) for its in vitro efficacy, gross inhibition, and mechanism of inhibition.Methods: The fibroblasts were treated with pre-specified concentrations of NAM followed by measurement of the cell proliferation using CCK-8 assay. The production of reactive oxygen species (ROS) was measured by 2ʹ,7ʹ-Dichlorofluorescin diacetate. We further investigated the apoptosis by flow cytometry using Annexin-V. We employed JC-1 assay to detect changes in the potential of the mitochondrial membrane. We further determined the expression of apoptotic genes was measured using qRT-PCR. And lastly, cell cycle experiments were conducted to determine the influence of NAM on arresting the growth of CAF in a cell cycle.Results: Our study showed that NAM was able to reduce fibroblasts viability. We specifically observed a significantly increased intracellular ROS with resultant exhaustion of cellular antioxidant defense machinery, including reduced glutathione (GSH). We further observed the involvement of mitochondrial pathway in the NAM induced apoptosis of fibroblasts.Conclusion: Our study supports the therapeutic potential of NAM for the treatment of cervical cancer and necessitates a further investigation of the reported findings.Keywords: apoptosis, cervical cancer, fibroblasts, mitochondrial pathway, nicotinamide, therapeutic potential

Zhi-Zhou Shi,1,* Ze-Wen Fan,1,* Yun-Xia Chen,1 Xiu-Feng Xie,1 Wen Jiang,2 Wen-Jun Wang,1 Yun-Tan Qiu,1 Jie Bai1 1Medical School, Kunming University of Science and Technology, Kunming, People’s Republic of China; 2Department of Thoracic Surgery, The First People’s Hospital of Yunnan Province, Kunming, People’s Republic of China*These authors contributed equally to this workCorrespondence: Zhi-Zhou Shi; Jie BaiMedical School, Kunming University of Science and Technology, No. 727 Jingming South Road, Kunming 650500, People’s Republic of ChinaEmail zhizhoushi@126.com; jiebai662001@126.comAbstract: Ferroptosis is a new form of programmed cell death with characteristic accumulation of reactive oxygen species (ROS) resulting from iron accumulation and lipid peroxidation. Ferroptosis is involved in many diseases, including cancer, and induction of ferroptosis has shown attractive antitumour activities. In this review, we summarize recent findings on the regulatory mechanisms of key regulators of ferroptosis, including the catalytic subunit solute carrier family 7 member 11 (SLC7A11), the glutathione peroxidase 4 (GPX4), p53 and non-coding RNAs, the correlations between ferroptosis and iron homeostasis or autophagy, ferroptosis-inducing agents and nanomaterials and the diagnostic and prognostic value of ferroptosis-associated genes in TCGA data.Keywords: ferroptosis, cancer, iron, autophagy, p53

Lin Liu,1,* Dongyu Xie,2,3,* Haina Xie,4,* Wei Huang,1 Jingxian Zhang,5 Wenye Jin,5 Wenjing Jiang,1 Donghao Xie5,6 1Department of Pharmacy, Dahua Hospital, Shanghai, People’s Republic of China; 2Department of Spleen-Stomach, Zhenjiang Affiliated Hospital of Nanjing University of Chinese Medicine, Zhenjiang, People’s Republic of China; 3Department of Spleen-Stomach, Zhenjiang Hospital of Traditional Chinese Medicine, Zhenjiang, People’s Republic of China; 4School of Basic Medical Sciences, Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China; 5Department of Pharmacy, Guanghua Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai, People’s Republic of China; 6School of Pharmacy, Jiangsu University, Zhenjiang, People’s Republic of China*These authors contributed equally to this workCorrespondence: Donghao XieDepartment of Pharmacy, Guanghua Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai, People’s Republic of ChinaTel +86- 18221220090Email xdhdh2012@126.comIntroduction: ARHGAP10 belongs to the ARHGAP family, which is downregulated in certain human tumors. However, the detailed function of ARHGAP10 remains unclear in human colon carcinoma (CRC). In the current study, we aimed to explore the role of ARHGAP10 in the growth and metastasis of CRC cells.Methods: ARHGAP10 was induced silencing and overexpression using RNA interference (RNAi) and lentiviral-vector in CRC cells. Quantitative real-time PCR (qRT-PCR) and Western blot were used to quantify the mRNA and protein contents of ARHGAP10. Cell proliferation was determined by using Cell counting kit-8 (CCK-8). Transwell assay was utilized to examine the role of ARHGAP10 in the migration and invasion of CRC cells.Results: Our results indicated that ARHGAP10 was downregulated in human CRC tissues and low expression of ARHGAP10 was associated with poor prognosis of patients with CRC. Moreover, ARHGAP10 overexpression significantly inhibited the proliferation and metastasis of CRC cells. Moreover, a PI3K/AKT inhibitor LY294002 was utilized to examine the connection between ARHGAP10 and AKT. Our findings demonstrated that the AKT inhibitor LY294002 could rescue the function of ARHGAP10 in CRC cells.Discussion: It was the first time to elucidate that AKT involved in the ARHGAP10 signaling pathway and ARHGAP10 negatively mediated the phosphorylation of AKT (p-AKT) and RhoA activity in CRC cells. Interestingly, the Rho/MRTF/SRF inhibitor CCG-1423 significantly inhibited the phosphorylation of AKT in ARHGAP10 siRNA transfected CRC cells. Much importantly, overexpression of ARHGAP10 deeply suppressed the metastasis of CRC cells in the lung in vivo. Taken together, our findings not only enhanced the understanding of the anti-cancer effect of ARHGAP10 in CRC cells but also indicated its underlying pathway in CRC.Keywords: ARHGAP10, AKT, RhoA activity, colon carcinoma

Wei Jiang,1,2,* Tao Li,1,2,* Jingjing Wang,1,2 Ruonan Jiao,1,2 Xiao Shi,1,2 Xiaodan Huang,1,2 Guozhong Ji1,2 1Department of Gastroenterology, The Second Affiliated Hospital of Nanjing Medical University, Nanjing 210011, People’s Republic of China; 2Jiangsu Key Laboratory of Cancer Biomarkers, Prevention And Treatment, Collaborative Innovation Center For Cancer Personalized Medicine, Nanjing Medical University, Nanjing 211166, People’s Republic of China*These authors contributed equally to this workCorrespondence: Guozhong JiDepartment of Gastroenterology, The Second Affiliated Hospital of Nanjing Medical University, Nanjing 210011, People’s Republic of ChinaEmail jgz@njmu.edu.cnBackground: A variety of miRNAs have been recently reported to be abnormally expressed in colorectal cancer (CRC). A growing number of studies have demonstrated that aberrantly expressed miRNAs are closely related to the development and progression of CRC. It has been found that miR-140-3p plays a vital role in several cancers. However, its expression, roles and mechanisms in CRC are remain unknown.Materials and methods: Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) were used to determine miR-140-3p expression in CRC tissues and cell lines. CCK8, migration, invasion and flow cytometric assays were used to determine the influence of miR-140-3p upregulation on cell proliferation, migration, invasion and apoptosis of CRC cells. Luciferase reporter assays and Western blots were utilized to identify the target genes of miR-140-3p. In addition, the potential mechanism of miR-140-3p action in CRC cells was elucidated.Results: In our study, miR-140-3p expression was significantly decreased in CRC tissues and cell lines. Overexpression of miR-140-3p attenuated proliferation, migration, and invasion and induced the apoptosis of CRC cells. Bioinformatics analyse and luciferase reporter analysis identified PD-L1 as a putative target gene of miR-140-3p. PD-L1 was overexpressed in CRC tissues and inversely correlated with miR-140-3p expression. Suppression of PD-L1 expression in CRC cells generated biological behaviours in CRC cells that were similar to those observed after treated with miR-140-3p mimics. Restoration of PD-L1 expression partially attenuated the inhibitory effect of miR-140-3p on CRC cells. Western blot were used to verify the effect of PD-L1 expression on PI3K/AKT pathway. In addition, overexpression of miR-140-3p could inhibit CRC tumor growth in vivo.Conclusion: In general, these data demonstrate that miR-140-3p acts as a tumour suppressor in CRC by directly targeting PD-L1 and inactivating PI3K/AKT pathway, suggesting that miR-140-3p might be a novel target for CRC diagnosis and treatment.Keywords: microRNA-140-3p, PD-L1, colorectal cancer, apoptosis

Ye Cheng,1,* Hanzhi Sun,1,* Hanjin Wang,1,* Wei Jiang,1 Weiwei Tang,1 Chen Lu,1 Wenling Zhang,2 Ziyi Chen,3 Chengyu Lv1 1Department of General Surgery, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu, People’s Republic of China; 2Department of Gastroenterology, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu, People’s Republic of China; 3Department of General Surgery, Zhongda Hospital, Medical School, Southeast University, Nanjing, Jiangsu, People’s Republic of China*These authors contributed equally to this workCorrespondence: Chengyu LvDepartment of General Surgery, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu, People’s Republic of ChinaEmail lcy_1234@aliyun.comZiyi ChenDepartment of General Surgery, Zhongda Hospital, Medical School, Southeast University, Nanjing, Jiangsu, People’s Republic of ChinaEmail dr_czy@126.comAbstract: Circular RNAs (circRNAs) are a recently discovered subclass of non-coding RNAs (ncRNAs) characterized by a covalently closed loop structure created by reverse splicing. Because they do not have a 5ʹ cap structure and a 3ʹ poly A tail, circRNAs have higher stability, abundance and evolutionary conservation than linear RNA between species. These features produce various potential biological functions of circRNAs, such as miRNA sponges, RNA-binding proteins that form RNA protein complexes. In recent years, more and more studies have shown that circRNAs play a vital role in the occurrence and development of human diseases. At the same time, their enormous potential as a biomarker and therapeutic target is also evolving. The purpose of this review is to summarize existing cancer-associated circRNAs and to try to find circRNAs that are abnormally expressed in many cancers. Therefore, we reviewed previous circRNAs studies related to cancer and selected them by statistics. The eight circRNAs that have the highest frequency in different cancers or involve key pathways are called star circRNAs. Here, we review the classification, features, and functions of emerging star circRNAs, with particular attention to the role of circRNAs in various cancers.Keywords: circular RNA, cancer, targeted therapy, diagnosis

Shaozhang Zhou, Huilin Wang, Wei Jiang, Qitao Yu Department of Respiratory Oncology, Guangxi Medical University Affiliated Tumor Hospital, Nanning 530021, People’s Republic of ChinaCorrespondence: Qitao YuDepartment of Respiratory Oncology, Guangxi Medical University Affiliated Tumor Hospital, No.71, Heti Road, Nanning 530021, Guangxi, People’s Republic of ChinaTel +86 0771 533 4955Fax +86 0771 530 0613Email qty178@163.comObjective: This study analyzed the relationship between the clinicopathological features and epidermal growth factor receptor (EGFR) mutation status of squamous cell lung cancer (SqCLC) patients. Mutation status was analyzed by comparing the amplification refractory mutation system-polymerase chain reaction (ARMS-PCR) and next-generation sequencing (NGS). We also assessed the efficacies of EGFR tyrosine kinase inhibitors (TKIs).Methods: Retrospective analysis was performed for 292 SqCLC patients treated at the Guangxi Medical University Affiliated Tumor Hospital from December 2013 to December 2018. The EGFR mutations in tumor tissues were identified by ARMS-PCR and NGS. The affiliation between EGFR mutation and clinicopathological features was analyzed. Efficacies of EGFR-TKIs and survival were evaluated using the benchmarks of response evaluation criteria in solid tumors 1.1 (RECIST 1.1) and the Kaplan–Meier method, respectively.Results: Among the 292 SqCLC patients, 24 (8.2%) were identified to have an EGFR-sensitizing mutation. Both ARMS-PCR and NGS were equally effective in detecting EGFR mutations. Females and non-smokers had higher EGFR mutation rates than males and smokers (22.1% vs. 5.1%, P = 0.007 and 16.7% vs. 4.5%, P = 0.001, respectively). EGFR mutation was unrelated to the degree of differentiation, clinical stage, specimen type and level of serum carcino-embryonic antigen (CEA) and squamous cell carcinoma antigen (SCC) (P > 0.05). In the 14 EGFR mutant cases treated with EGFR-TKIs, the objective response rate (ORR) and disease control rate (DCR) were 28.6% and 78.6%, respectively. Median progression-free survival (mPFS) and overall survival (mOS) were 4.9 and 10.75 months, respectively, with fine tolerance and mild side-effects.Conclusion: EGFR-sensitizing mutations are rare in SqCLC patients with females and non-smokers having a higher risk of harboring them. There was no difference in the detection rates of EGFR for both the ARMS-PCR and NGS methods. EGFR-TKIs showed modest efficacies and low toxicity profiles in EGFR mutant cases.Keywords: squamous cell lung carcinoma, epidermal growth factor receptor mutation, clinicopathologic features, tyrosine kinase inhibitors

Lin Li,1,2Zuohui Zhao,3 Wenguo Jiang,2 Jisheng Guo,1 Shuping Zhang41Cancer Research Center, School of Basic Medical Sciences, Shandong University, Jinan, Shandong 250012, People’s Republic of China; 2Medicine and Pharmacy Research Center, Binzhou Medical University, Yantai, Shandong 264003, People’s Republic of China; 3Departments of Urology and Pediatric Surgery, Shandong Provincial Qianfoshan Hospital, Jinan, Shandong, 250021, People’s Republic of China; 4Department of Pharmacology, School of Pharmaceutical Sciences, Binzhou Medical University, Yantai 264003, People’s Republic of ChinaBackground: Trimethylation of histones has been extensively studied, where histone methyltransferases catalyze the transfer of methyl groups from S-adenosyl methionine. Thus far, there have been no researches on the trimethylation of non-histone proteins. The precise mechanisms by which trimethylation affects cell progress and the related protein functions remain unclear.Purpose: The objective of this study was to identify the Lys-trimethylated proteins in kidney-derived cells and tissues, as well as to better understand the mechanisms underlying Lys-trimethylation-mediated cell metabolism.Methods: The levels of Lys-trimethylation in kidney-derived cells and tissues were assayed by Western blotting. Additionally, high-resolution mass spectrometry was used to analyze kidney-derived cells and tissues, and the eukaryotic expression vectors that led to the mutations of lysine were constructed and transfected into HEK293T cells. The LDHA activity of HEK293T cells was detected under conditions of Lys-trimethylation inhibition, and the proliferation of HEK293T cells was measured using EdU and Western blotting analyses.Results: The different proteins in kidney-derived cells and tissues showed different levels of Lys-trimethylation. In particular, lactate dehydrogenase A (LDHA) was Lys-trimethylated on lysine (K5). Inhibition of the Lys-trimethylation in LDHA increased the LDH activity of HEK293T cells and upregulated their proliferation.Conclusion: We suggested that LDHA affects the metabolism and proliferation of cells via a Lys-trimethylation-mediated mechanism; Lys-trimethylation might be a potential target for therapeutic research or used as a prognostic and treatment biomarker of several diseases.Keywords: trimethylation, lactate dehydrogenase A, liquid chromatography-tandem mass spectrometry, cell, kidney cancer, proliferation

Huiying Fang, Wei Jiang, Zhouhong Jing, Xiaosong Mu, Zhongxun XiongDepartment of Breast Disease, Chongqing University Cancer Hospital, Chongqing City, 400000, People’s Republic of ChinaBackground: Previous research had shown that an imbalance in cell proliferation and apoptosis is a vital mechanism for tumorigenesis and cancer progression that may directly influence biological behaviors of cancer. microRNAs are associated with the occurrence and development of tumors. This study aimed to explore the influence of miR-937 on breast cancer regulation of APAF1 expression.Methods: Cancer Genome Altas microarray analysis (fold change > 2, p

Wenjie Jiang,1 Yuan Chen,1 Xing Song,1 Yingjie Shao,1 Zhonghua Ning,1 Wendong Gu11Department of Radiation Oncology, The Third Affiliated Hospital of Soochow University, Jiangsu, Changzhou 213003, People’s Republic of ChinaBackground: In the present study, we aimed to investigate the effect of proviral integration site for moloney murine leukemia virus-1 (Pim-1) inhibitor (SMI-4a) on the progression of non-small cell lung cancer (NSCLC).Materials and methods: The effects of SMI-4a on proliferation, apoptosis, and cell cycle of NSCLC cells were examined by in vitro experiments using human NSCLC cell lines (A549 and Ltep-a-2). The pathway regulated by SMI-4a was detected using Western blot. Furthermore, we performed in vivo experiments to assess the effects of SMI-4a on tumor growth using mouse models with NSCLC.Results: Our data demonstrated that SMI-4a could inhibit the proliferation of A549 and Ltep-a-2 cells markedly in a dose-dependent manner (P

Wen Jiang,* Jiali Xu,* Rong Wang, Tingting Wang, Yongqian Shu, Lianke Liu Department of Oncology, the First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China *These authors contributed equally to this work Background: Merkel cell carcinoma (MCC) is a kind of cutaneous neuroendocrine cancer with a poor prognosis. It is characterized by a high rate of recurrence and metastases, including distant metastases and regional nodal metastases. Clinically, MCC often manifests as obvious single painless hard nodules visible in sun irradiation of diameter 2 cm, with rapid growth and metastases, especially lymph node metastases. Due to the aspecific nature of MCC, it is often confused with other skin cancers. Exploring different treatments of MCC is necessary.Case presentation: The current study describes the case of an 86-year-old retired man, who presented with a 2.5×2.0×1.2 cm red nodule on the right thigh, which was initially diagnosed as subcutaneous small cell cancer. Upon histological and immunohistochemical analysis, the tumor was consistent with a diagnosis of MCC.Results: Antiangiogenic therapy combining endostar and apatinib was administered and a partial response achieved after 2.0 months of treatment, and 6.5 months of progression-free survival was achieved. Overall survival was 13.0 months.Conclusion: We believe that antiangiogenic therapy is an extremely effective treatment for MCC, especially for patients who cannot tolerate chemotherapy and radiotherapy. Keywords: Merkel cell carcinoma, antiangiogenic therapy, endostar, apatinib

Xianwei Li, Bo Chen, Decai Chi, Yingnan Zhang, Weiliang Jiang Department of Vascular Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin 150001, Heilongjiang, People’s Republic ofChina Background: Despite being one of the most common benign tumors, the prevalence and pathogenesis of hemangiomas (HAs) are poorly understood. We aimed to identify the biological role of the long non-coding RNA (lncRNA) CASC9 in the HA-derived endothelial cell (HDECs) phenotype as well as elucidate the mechanism involved. Methods: The expression of CASC9 was identified by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). the effect of CASC9 on cell proliferation, migration and invasion of HDECs were examined by CCK8, wound healing, and transwell assay, respectively. Bioinformatics analysis and a luciferase reporter assay were utilized to investigated the mechanisms involved. The in vivo tumorigenesis capability of CASC9 on HA was also evaluated. Results: The expression of CASC9 was significantly elevated in HA tissue compared to normal tissue. Down-regulation of CASC9 inhibited proliferation, migration, and invasion of HDECs. The translation of cyclinD1, N-cadherin, Twist, and MMP2 was also decreased by CASC9 knockdown treatment. Furthermore, CASC9 over-expression exerted the opposite effect of proliferation, migration, and invasion of HDECs. We also found that CASC9 interacts with miR-125a-3p/Nrg1 to regulate cellular functions. Interestingly, miR-125a-3p can reverse the effect of CASC9 on proliferation, migration, and invasion of HDECs. Together, the clinical data showed that CASC9 expression is negatively correlated with miR-125a-3p expression and positively correlated with Nrg1 expression. CASC9 also exerted anti-tumorigenesis capability in vivo. Conclusion: Our study indicates that CASC9 accelerates cell growth and invasion of HDECs and provides new insights for the diagnosis and molecular therapy of HA. Keywords: CASC9, cell migration, invasion, hemangioma, miR-125a-3p, Nrg1

Jisan Sun, Wentao Jiang, Dazhi Tian, Qingjun Guo, Zhongyang Shen Department of Liver Transplantation, Tianjin First Center Hospital, First Clinical Institute of Tianjin Medical University, Nan Kai District, Tianjin 300192, People’s Republic of China Purpose: Hepatocellular carcinoma (HCC) accounts for one of the most prevalent tumor types in the world and still lacks an effective treatment regimen. The EGFR tyrosine-kinase inhibitor icotinib is capable of inhibiting proliferation of several kinds of cancer cells, but its anticancer effect in HCC is still not verified.Methods: In the current study, ten HCC cell lines were selected to test their original EGFR-activation status and PDL1 protein level, and in vitro antiproliferation assays were also conducted to analyze the IC50 and further investigate the correlation between IC50 and protein level of phosphorylated EGFR and PDL1. A in vivo nude mouse xenograft animal model was used as well to analyze its anticancer effect.Results: Icotinib showed significant inhibitory effects only on HCC cell lines that had both higher p-EGFR and PDL1 protein level. This specific HCC cell line was subcutaneously injected to establish the in vivo xenograft tumor model, and icotinib reduced tumor weight remarkably and growth dose dependently. Molecular mechanism study revealed that icotinib inhibited the phosphorylation of EGFR and PDL1 expression in cancer cells and activated apoptosis. Knocking down PDL1 significantly reduced the inhibitory effect of icotinib on HCC, and knocking in PDL1 increased the sensitivity of icotinib in HCC.Conclusion: The current research suggests that icotinib has an inhibitory effect on a subgroup of HCC cells that have both higher p-EGFR and PDL1. This hints at the potential clinical usage of icotinib in HCC based on PDL1-biomarker examination. Keywords: hepatocellular carcinoma, epidermal growth factor receptor, icotinib, PDL1 protein

Weifang Jiang,1,* Weiji Yang,2,* Li Yuan,3 Fanlong Liu3 1Department of Surgery, The Hospital of Zhejiang University, Hangzhou 310016, China; 2Graduate Student Department, Zhejiang Chinese Medical University, Hangzhou 310053, China; 3Department of Anorectal Surgery, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, China *These authors contributed equally to this work Background: A kinase-interacting protein 1 (AKIP1) has been reported to play an important role in the development and progression of cancer. However, the clinicopathological and biological roles of AKIP1 in colorectal cancer (CRC) remain largely unknown. The aim of this study was to investigate AKIP1 protein expression in CRC and determine the correlation between AKIP1 protein expression and clinicopathological features, as well as prognosis in CRC patients.Materials and methods: AKIP1 protein expression was determined by immunohistochemical analysis using tissue microarrays of CRC. We also used an siRNA approach to knock down AKIP1 expression and determine the effect of AKIP1 on CRC cell migration by transwell analysis.Results: AKIP1 expression in CRC tissue was significantly higher compared with that of noncancerous colorectal mucosa (P

Liang Zeng,* Yizhi Li,* Lili Xiao,* Yi Xiong, Li Liu, Wenjuan Jiang, Jianfu Heng, Jingjing Qu, Nong Yang, Yongchang Zhang Department of Medical Oncology, Lung Cancer and Gastrointestinal Unit, Hunan Cancer Hospital/The Affiliated Cancer Hospital of Xiangya School of Medicine, Changsha 410013, China *These authors contributed equally to this work Introduction: Data of standard tyrosine kinase inhibitor (TKI) treatment outcome in next-generation sequencing (NGS)-identified ROS1-rearranged non-small-cell lung cancer (NSCLC) were rare. Thus, it is practical and necessary to evaluate the efficacy and influential factors of crizotinib in real-world practice.Patients and methods: A total of 1,466 NSCLC patients with positive targeted NGS test results from September 2015 to January 2018 were enrolled in this real-world retrospective study. Twenty-two patients had ROS1 rearrangement detected by NGS. The efficacy and safety of crizotinib were evaluated. Subgroups of concomitant mutations, brain metastasis, and fusion variants were also analyzed.Results: Among all the patients, the occurrence rate of ROS1 rearrangement was 1.5% (22 of 1,466). Ten ROS1 fusion partners were detected, and the most common variant was CD74, which accounted for 50% (11 of 22). Five patients were found to carry dual ROS1 fusion partners, and 23% (5 of 22) of patients were detected with concomitant mutations, including TP53&PIK3CA&mTOR mutation, TP53&CDKN2A mutation, TP53&BRCA2 mutation, ALK missense mutation (p.R311H), and MET amplification. Among 22 patients with ROS1-rearranged NSCLC, 20 patients were diagnosed at stage IV, and 19 patients received crizotinib treatment. The average follow-up period was 16 months. The overall response rate (ORR) of crizotinib in unselected crizotinib-treated patients was 89%, and the median progression-free survival time (mPFS) was 13.6 months. It was shown that NSCLC patients with exclusive ROS1 rearrangement had a longer PFS than those carrying concomitant mutations (15.5 vs 8.5 months, P=0.0213). There were no newly occurring intolerant adverse events in this study.Conclusion: Crizotinib is highly effective in NGS-identified ROS1-rearranged advanced NSCLC in real-word clinical practice, and the data are consistent with previous clinical trials applying fluorescence in situ hybridization/real-time PCR for ROS1 companion diagnosis. Concomitant mutations may not be rare and may deteriorate the PFS of crizotinib in patients with ROS1-rearranged NSCLC. Keywords: ROS1, next-generation sequencing, crizotinib, concomitant mutation, NSCLC, efficacy, TP53, safety&nbsp

Hui Chang,1,2,* Wu Jiang,1,3,* Wei-Jun Ye,1,2 Ya-Lan Tao,1,2 Qiao-Xuan Wang,1,2 Wei-Wei Xiao,1,2 Yuan-Hong Gao1,2 1State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, People’s Republic of China; 2Department of Radiation Oncology, Sun Yat-sen University Cancer Center, Guangzhou, People’s Republic of China; 3Department of Colorectal Surgery, Sun Yat-sen University Cancer Center, Guangzhou, People’s Republic of China *These authors contributed equally tothiswork Objectives: To evaluate the impact of interval between neoadjuvant chemoradiotherapy (NACRT) and surgery on therapeutic and adverse effects of surgery, and long-term outcome of patients with locally advanced rectal cancer (RC), in the era of intensity-modulated radiotherapy (IMRT).Patients and methods: Patients diagnosed with stage II–III RC and treated with IMRT-based NACRT followed by radical surgery were enrolled consecutively from April 2011 to March 2014. The data of all the patients were collected prospectively and grouped according to their NACRT-to-surgery interval. The therapeutic and adverse effects of surgery, and survivals were compared between the patients with interval ≤7 weeks and those with interval ≥8 weeks.Results: A total of 231 patients were eligible for analysis, including 106 cases with interval ≤7 weeks and 125 cases with interval ≥8 weeks. The therapeutic and adverse effects of surgery were similar between these two groups of patients. However, interval ≥8 weeks appeared to lead to poorer overall, distant-metastasis-free and disease-free survivals, compared with interval ≤7 weeks. The HRs were 1.805, 1.714, and 1.796 (P-values were 0.045, 0.049, and 0.028), respectively.Conclusion: For patients with locally advanced RC, a long NACRT-to-surgery interval might bring a potential risk of increased distant metastasis rather than a better tumor regression in the era of IMRT. Keywords: rectal cancer, interval, neoadjuvant chemoradiotherapy, surgery, survival

Wei Jiang,1,* Qitao Yu,1,* Ruiling Ning,1 Wenhua Zhao,1 Changyuan Wei2 1Department of Medical Oncology, Tumor Hospital Affiliated to Guangxi Medical University, Nanning, People’s Republic of China; 2Department of Breast Surgery, Tumor Hospital Affiliated to Guangxi Medical University, Nanning, People’s Republic of China *These authors contributed equally tothis work Background: Results from several prospective clinical trials comparing anti-epidermal growth factor receptor (EGFR) therapy and anti-vascular endothelial growth factor (VEGF) therapy plus chemotherapy for wild-type RAS metastatic colorectal cancer (mCRC) have been inconsistent. This meta-analysis aims to investigate the optimal choice for these target agents. Methods: We searched for clinical trials in both electronic databases from inception until January 2018 and recent conference abstracts to identify prospective clinical studies comparing the efficacy of a VEGF inhibitor (bevacizumab) versus EGFR inhibitors (cetuximab or panitumumab) on wild-type RAS (including its subset KRAS) mCRC. All analyses were conducted using RevMan 5.3 software. Results: A total of 5 studies were included. EGFR inhibitors were associated with a significant benefit in terms of overall survival (OS) compared with VEGF inhibitors in wild-type KRAS or wild-type RAS populations, with hazard ratios (HRs) equal to 0.86 (95% CI: 0.78, 0.95; p=0.003) and 0.83 (95% CI: 0.72, 0.95; p=0.007), respectively. This survival benefit was limited to the first-line setting. No difference was found for progression-free survival (PFS), whereas the objective response rate (ORR) was significantly increased in the wild-type RAS population (OR: 0.64; 95% CI: 0.50, 0.82; p=0.0004). No difference in OS was noted between EGFR inhibitors versus a VEGF inhibitor plus the FOLFIRI regimen, whereas superior survival was noted for EGFR inhibitors plus the mFOLFOX6 regimen versus a VEGF inhibitor (HR: 0.75; 95% CI: 0.57, 0.98; p=0.04). PFS was significantly prolonged (HR: 1.48; 95% CI: 1.14, 1.92; p=0.003), whereas a trend favoring OS (HR: 1.23; 95% CI: 0.93, 1.63; p=0.14) was noted for a VEGF inhibitor in patients with right-sided tumors, with no difference in the ORR (OR: 0.85; 95% CI: 0.52, 1.38; p=0.51). However, left-sided tumors exhibited superior OS (HR: 0.71; 95% CI: 0.59, 0.85; p=0.0002), PFS (HR: 0.84; 95% CI: 0.72, 0.98; p=0.03), and ORR (OR: 0.66; 95% CI: 0.48, 0.92; p=0.01) for EGFR inhibitors. Conclusion: This meta-analysis suggests the superiority of anti-EGFR therapy compared with anti-VEGF therapy for mCRC with wild-type RAS. Primary tumor location should be taken into account in target drug selection. Further research is still needed to confirm which inhibitor may be a better choice when combined with different chemotherapy regimens. Keywords: bevacizumab, cetuximab, panitumumab, colorectal cancer, meta-analysis

Yang Jia, Zhaohua Xiao, Xin Gongsun, Zhongwei Xin, Bin Shang, Gang Chen, Zhou Wang, Wenpeng Jiang Department of Thoracic Surgery, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, China Background: Centrosomal protein 55 (CEP55) is an important prognostic biomarker that plays an essential role in the proliferation, migration and invasion of multiple tumors. We aimed to investigate the prognostic value of CEP55 in pN0 esophageal squamous cell carcinoma (ESCC) and explore its biological function in ESCC cells.Methods: We used immunohistochemistry and Western blot analysis to detect the expression of CEP55 in ESCC. Furthermore, both in vitro and in vivo assays were used to determine the effect of CEP55 on malignant behavior in ESCC cells.Results: As expected, we found that CEP55 was overexpressed in ESCC. Univariate and multivariate analyses demonstrated that patients with CEP55 overexpression had a poor prognosis. Additionally, the abilities of proliferation, migration and invasion of cells, as well as the epithelial–mesenchymal transition markers, were all altered with the changed CEP55 expression levels in ESCC cells. Further study elucidated that CEP55 facilitated ESCC via the PI3K/Akt pathway. Blockade of this pathway markedly attenuated CEP55-mediated proliferation, migration, invasion and epithelial–mesenchymal transition of ESCC cells.Conclusion: Oncogenic CEP55 correlates with a poor prognosis by regulating tumor cell proliferation, migration and invasion via the PI3K/Akt pathway. It can serve as a promising prognostic biomarker and therapeutic target of pN0 ESCC after Ivor-Lewis esophagectomy. Keywords: CEP55, proliferation, migration, invasion, esophageal squamous cell carcinoma, PI3K/Akt pathway

Ke Ma,* Fenghao Sun,* Xiaodong Yang, Shuai Wang, Lin Wang, Yulin Jin, Yu Shi, Wei Jiang, Cheng Zhan, Qun Wang Department of Thoracic Surgery, Zhongshan Hospital of Fudan University, Shanghai, People’s Republic of China *These authors contributed equally to this work Background: The aim of this study was to identify risk factors for patients with malignant main stem bronchial tumors (MBTs) and to develop a nomogram for predicting prognosis in those patients using data from the Surveillance, Epidemiology, and End Results (SEER) database.Method: A process was used for case screening from the SEER database. The effect of prognostic factors on survival was evaluated using the Kaplan–Meier method and log-rank test, a competing risk model, and the Cox proportional hazards regression model. A nomogram was established for predicting 1-, 3-, and 5-year overall survival (OS) in patients with MBTs.Results: A total of 7,418 cases were included in this study. Age, gender, pathologic grade, histologic type, tumor size, involvement of lymph nodes, tumor extension, chemotherapy, and surgery were identified as independent risk factors by univariate and multivariate analyses. A nomogram was established based on the results of the Cox model, which was validated by a C-index of 0.672 (95% CI, 0.664–0.680), and a group of calibration plots.Conclusion: Age, gender, pathologic grade, histologic type, tumor size, involvement of lymph nodes, tumor extension, chemotherapy, and surgery were independent risk factors for OS of patients with MBTs. A nomogram was formulated to predict 1-, 3-, and 5-year OS in patients with MBTs based on individual clinical characteristics. Keywords: malignant main stem bronchial tumor, nomogram, prognosis, risk factors

Jiang W, Li T, Wang J, et al. Onco Targets Ther.2019;12:10275–10285.The authors have advised that the Acknowledgement onpage 10,284 is incorrect. The text “This study was supportedby the Primary Research & Development Plan ofJiangsu Province grant (NO. BE2016799) and theResearch Innovation Program for Graduates of JiangsuProvince grant (KYCX18-14)” should read “This studywas supported by the Primary Research & DevelopmentPlan of Jiangsu Province grant (NO. BE2016799) and theResearch Innovation Program for Graduates of JiangsuProvince grant. (KYCX18-1493)”.The authors apologize for this error.Read the original article

Yusheng Li,1 Chao Zeng,1 Min Tu,2 Wei Jiang,3 Zixun Dai,4 Yuling Hu,5 Zhenhan Deng,1 Wenfeng Xiao1 1Department of Orthopedics, Xiangya Hospital Central South University, Changsha, Hunan, 2Department of Orthopedics, Second People’s Hospital of Jingmen, Jingmen, Hubei, 3Department of Bone and Joint, Shenzhen People’s Hospital, Second Clinical Medical College of Jinan University, Shenzhen, Guangdong, 4Department of Orthopedics, The Affiliated Cancer Hospital of Xiangya School of Medicine, 5Department of Clinical Medicine, Xiangya School of Medicine, Central South University, Changsha, Hunan, People’s Republic of China Abstract: Osteosarcoma is the most common type of cancer that develops in bone, mainly arising from the metaphysis of the long bones. MicroRNA (miR)-200b has been found to generally act as a tumor suppressor in multiple types of human cancers. However, the detailed role of miR-200b in osteosarcoma still remains to be fully understood. This study aimed to investigate the exact role of miR-200b in the progression of osteosarcoma and the underlying mechanism. Real-time reverse transcription-polymerase chain reaction data showed that miR-200b was significantly downregulated in osteosarcoma tissues compared to their matched adjacent nontumor tissues. Low miR-200b level was associated with the advanced clinical stage and positive distant metastasis. Besides, it was also downregulated in osteosarcoma cell lines (U2OS, Saos2, HOS, and MG63) compared to normal osteoblast cell line NHOst. In vitro study showed that restoration of miR-200b led to a significant decrease in proliferation, migration, and invasion of osteosarcoma cells. Moreover, ZEB1 was identified as a target gene of miR-200b, and its expression levels were negatively mediated by miR-200b in osteosarcoma cells. In addition, ZEB1 was significantly upregulated in osteosarcoma cells compared to the normal osteoblast cell line NHOst, and inhibition of ZEB1 expression also suppressed the proliferation, migration, and invasion in osteosarcoma cells. Finally, we showed that ZEB1 was frequently upregulated in osteosarcoma tissues compared to their matched adjacent normal tissues, and its expression was reversely correlated to the miR-200b levels in osteosarcoma tissues. Based on these findings, our study suggests that miR-200b inhibits the proliferation, migration, and invasion of osteosarcoma cells, probably via the inhibition of ZEB1 expression. Therefore, miR-200b/ZEB1 may become a potential target for the treatment of osteosarcoma. Keywords: osteosarcoma, microRNA-200b, proliferation, migration, invasion, metastasis

Zongheng Zhu,1 Jinshan Zhang,2 Wei Jiang,3 Xianjue Zhang,4 Youkong Li,4 Xiaoming Xu51Department of General Surgery, Huangshi Love & Health Hospital, Huangshi, 2Department of Tumor surgery, Huangshi Central Hospital, Huangshi, 3Department of Urinary Surgery, Huangshi No 5 Hospital, Huangshi, 4Department of Urinary Surgery Jingzhou Central Hospital, Jingzhou, 5Department of Bone Surgery, Jingzhou Central Hospital, Jingzhou, People’s Republic of ChinaBackground: It is known that bladder cancer disease is closely related to aromatic amine compounds, which could cause cancer by regulating of N-acetylation and N-acetyltransferase 1 and 2 (NAT1 and NAT2). The NAT2 slowed acetylation and would increase the risk of bladder cancer, with tobacco smoke being regarded as a risk factor for this increased risk. However, the relationship between NAT2 slow acetylation and bladder cancer is still debatable at present. This study aims to explore preliminarily correlation of NAT2 slow acetylation and the risk of bladder cancer.Methods: The articles were searched from PubMed, Cochran, McGrane English databases, CBM, CNKI, and other databases. The extraction of bladder cancer patients and a control group related with the NAT2 gene were detected by the state, and the referenced articles and publications were also used for data retrieval. Using a random effects model, the model assumes that the studies included in the analysis cases belong to the overall population in the study of random sampling, and considering the variables within and between studies. Data were analyzed using STATA Version 6.0 software, using the META module. According to the inclusion and exclusion criteria of the literature study, 20 independent studies are included in this meta-analysis.Results: The results showed that the individual differences of bladder cancer susceptibility might be part of the metabolism of carcinogens. Slow acetylation status of bladder cancer associated with the pooled odds ratio was 1.31 (95% confidence interval: 1.11–1.55).Conclusion: The status of NAT2 slow N-acetylation is associated with bladder cancer risks, and may increase the risk of bladder cancer.Keywords: N-acetyltransferase 2, NAT2 slow acetylation status, bladder cancer, meta-analysis

PTen loss is one of the most frequent events in prostate cancer both at the initiation stage and during late stage metastatic development. The mouse model of prostate-specific probasin-mediated Pten deletion leads to prostate intraepithelial neoplasia (PIN) leading to adenocarcinoma. Using this model, we analysed the miR and mRNA transcriptome profile of Pten −/− PIN versus wild type age-matched prostate tissues and analysed the effects of Pten loss on miR expression in the early neoplastic process. At the PIN stage, Pten loss significantly changed the expression of over 20 miRNAs and over 4000 genes. The observed miR expression indicated a strong immunological cohort, which is seen in many human and mouse cancers and is thought to derive from infiltrating B and T immune cells. However, upon in situ hybridisation, these immunologically related miRs did not correlate with immune cell location, and emanated from the prostate epithelium itself and not from the associated immune cells present. Growing Pten −/− prostate cells in culture showed that the overexpressed miRNAs seen in Pten −/− were directly in response to the overactive PI3 kinase pathway and were in part responsible in reducing target gene expression levels. Inhibition of PI3 kinase downstream regulators, or re-introducing wild type Pten cDNA reduced miR overexpression resulting in increased miR target gene expression. MiR inhibitors also showed this pattern, and synergised with an mTORC1 inhibitor. Overall, Pten deletion in the prostate epithelium activated a cohort of inflammation-related miRs usually associated with immune responses from B and T cells. These oncomiRs may then accelerate carcinogenesis.

Fei Xu,1,* Jingxun Wu,2,* Cong Xue,1,* Yuanyuan Zhao,1 Wei Jiang,3 Liping Lin,4 Xuan Wu,5 Yachao Lu,6 Hua Bai,7 Jiasen Xu,8 Guanshan Zhu,6 Li Zhang11State Key Laboratory of Oncology in South China, Department of Medical Oncology, Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong, People's Republic of China; 2Department of Medical Oncology, The First Affiliated Hospital of Xiamen University, Xiamen, Fujian, People's Republic of China; 3Department of Medical Oncology, Cancer Hospital of Guangxi Medical University and Guangxi Autonomous Regional Cancer Hospital, Nanning, Guangxi, People's Republic of China; 4Department of Oncology and Hemotology, Panyu Central Hospital, Guangzhou, Guangdong, People's Republic of China; 5Department of Chemotherapy, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, Guangdong, People's Republic of China; 6Innovation Center China, AstraZeneca Global R&D, Shanghai, People's Republic of China; 7Department of Thoracic Medical Oncology, Peking University School of Oncology, Beijing Cancer Hospital and Institute, Beijing, People's Republic of China; 8SurExam Bio-Tech Co, Ltd, Science City, Guangzhou, People's Republic of China *These authors contributed equally to this workBackground: Previous studies have reported that epidermal growth factor receptor (EGFR) mutation in tumor tissue and peripheral blood can predict the response to EGFR tyrosine kinase inhibitor (TKI) in non-small cell lung cancer (NSCLC). However, the heterogeneity of the sample sources makes it difficult to evaluate the detecting methodologies. The goal of this study is to compare different methods for analyzing EGFR mutation in blood and tumor tissue.Materials and methods: Fifty-one advanced NSCLC patients treated with gefitinib were included in the study. The EGFR mutation status of each patients' blood was analyzed by denaturing high-performance liquid chromatography (DHPLC), mutant-enriched liquidchip (ME-Liquidchip), and Scorpion Amplification Refractory Mutation System (Scorpion-ARMS) kits. EGFR mutation information in paired tumor samples detected by Scorpion-ARMS served as a reference. Comparative analyses were performed on mutation status results obtained from different methods and on the association between the clinical outcome of TKI treatment and EGFR mutation status.Results: The response rate (RR) in the whole group was 33.3%. EGFR mutation rates were identified as 15.7%, 27.5%, and 29.4% by DHPLC, ME-Liquidchip, and Scorpion-ARMS in blood, respectively. In 34 cases that had paired tumor samples, the mutation rate in tissue was 41.2%. The RRs of patients with mutation detected by different methods were 71.4% (tumor), 62.5% (blood, DHPLC), 50.0% (blood, ME-Liquidchip), and 66.7% (blood, Scorpion-ARMS). EGFR mutation detected by Scorpion-ARMS in blood and tumor tissues had better prediction of RR to EGFR-TKI (P = 0.002 and P = 0.001) than mutation detected with DHPLC and ME-Liquidchip.Conclusion: Tumor tissue sample is the best source for EGFR mutation analysis in NSCLC patients. Peripheral blood samples may be used as an alternative source only in special conditions. Scorpion-ARMS, DHPLC, or ME-Liquidchip methods are all optional for detecting tumor EGFR mutation from blood.Keywords: non-small cell lung cancer, EGFR mutation, mutation detection methods, gefitinib