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Simin Liu,1,* Ming Feng,2,* Tingting Qiao,1,* Haidong Cai,1 Kele Xu,3 Xiaqing Yu,1 Wen Jiang,1 Zhongwei Lv,1 Yin Wang,2 Dan Li1 1Department of Nuclear Medicine, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai, People’s Republic of China; 2School of Electronic and Information Engineering, Tongji University, Shanghai, People’s Republic of China; 3National Key Laboratory of Parallel and Distributed Processing, National University of Defense Technology, Changsha, People’s Republic of China*These authors contributed equally to this workCorrespondence: Zhongwei Lv; Dan LiDepartment of Nuclear Medicine, Shanghai Tenth People’s Hospital, Tongji University, Yanchangzhong Road 301, Shanghai, 200072, People’s Republic of ChinaTel +86 21-66302075Email Lvzwjs2020@163.com; plumredlinda@163.comObjective: To develop an approach for automatically analyzing bone metastases (BMs) on bone scintigrams based on deep learning technology.Methods: This research included a bone scan classification model, a regional segmentation model, an assessment model for tumor burden and a diagnostic report generation model. Two hundred eighty patients with BMs and 341 patients with non-BMs were involved. Eighty percent of cases were randomly extracted from two groups as training set. Remaining cases were as testing set. A deep residual convolutional neural network with different structures was used to determine whether metastatic bone lesions existed, regions of lesions were automatically segmented. Bone scan tumor burden index (BSTBI) was calculated; finally, diagnostic report could be automatically generated. The sensitivity, specificity and accuracy of classification model were compared with three physicians with different clinical experience. The Dice coefficient evaluated the effect of segmentation model and compared to the result of nnU-Net model. The correlation between BSTBI and blood alkaline phosphatase (ALP) level was analyzed to verify the efficiency of BSTBI. The performance of report generation model was evaluated by the accuracy of interpretation of report.Results: In testing set, the sensitivity, specificity and accuracy of classification model were 92.59%, 85.51% and 88.62%, respectively. The accuracy showed no statistical difference with moderately and experienced physicians and obviously outperformed the inexperienced. The Dice coefficient of BMs area was 0.7387 in segmentation stage. Based on the whole model frame, our segmentation model outperformed the nnU-Net. BSTBI value changed as the BMs changed. There was a positive correlation between BSTBI and ALP level. The accuracy of report generation model was 78.05%.Conclusion: Deep learning based on automatic analysis frameworks for BMs can accurately identify BMs, preliminarily realize a fully automatic analysis process from raw data to report generation. BSTBI can be used as a quantitative evaluation indicator to assess the effect of therapy on BMs in different patients or in the same patient before and after treatment.Keywords: bone metastases, bone scintigraphy, deep learning, tumor burden, automatic report generation

Xiaojiao Zheng,1,2 Xiuyi Lv,1 Linyan Zhu,1 Kejun Xu,1 Cong Shi,1 Lining Cui,1 Huiqing Ding1 1Department of Obstetrics and Gynecology, Ningbo First Hospital, Ningbo, Zhejiang, 315035, People’s Republic of China; 2Department of Biochemistry & Genetics, The National Education Base for Basic Medical Sciences, Institute of Cell Biology, Zhejiang University School of Medicine, Hangzhou, 310058, Zhejiang Province, People’s Republic of ChinaCorrespondence: Lining Cui; Huiqing Ding Email 1935148739@qq.com; 1209256240@qq.comBackground: Mounting evidence indicates altered circadian rhythm represents a critical factor affecting carcinogenesis and tumor progression. The circadian gene neuronal PAS domain protein 2 (NPAS2) constitutes a newly discovered prognostic biomarker. NPAS2 dysregulation is found in multiple malignancies, although its functions in uterine corpus endometrial carcinoma (UCEC) remain largely unknown.Objective: To evaluate NPAS2’s roles in UCEC and to explore the underlying mechanisms.Methods: NPAS2 transcription levels, patient prognosis, different clinical stages and target microRNAs in UCEC cases were comparatively assessed based on public databases, including UALCAN, GEPIA, TIMER, Kaplan–Meier plotter, starBase database, LinkedOmics and String. Then, qRT-PCR and immunohistochemical analysis were applied to analyze the expression of NPAS2 in UCEC tissue samples. CCK-8, clonogenic assay and flow cytometry were carried out for detecting cell viability, colony formation ability and cell apoptosis, respectively.Results: NPAS2 was upregulated in tissue samples from UCEC cases compared with the corresponding control specimens. NPAS2 overexpression was associated with decreased overall (OS), disease free (DFS) and relapse free (RFS) survival in UCEC. In addition, NPAS2 overexpression was associated with clinical stage, tumor grade, estrogen receptor status, myometrial invasion in UCEC. Furthermore, NPAS2 knockdown or overexpression altered cell proliferation and apoptosis in UCEC. Moreover, NPAS2 showed significant negative correlations with miR-17-5p and miR-93-5p, and positive correlations with miR-106a-5p and miR-381-3p in UCEC.Conclusion: NPAS2 overexpression is associated with poor prognosis and clinicopathological characteristics in UCEC and promotes proliferation and colony formation while inhibiting apoptosis. Finally, NPAS2 is associated with several miRNAs in UCEC.Keywords: NPAS2, circadian rhythm, cell cycle, apoptosis, uterine corpus endometrial carcinoma

Jinbao Chen,1,* Wentao Wu,1,* Xue He,1 Linlin Jia,1 Jiahua Yang,1 Xianke Si,1 Kun Yu,1 Sen Li,1 Yanyan Qiu,1 Ke Xu,2 Peihao Yin,1,3 Yijun Cao,1 Qiong Li,4 Wei Li1 1Department of General Surgery, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China; 2Institute of Translational Medicine, Shanghai University, Shanghai, People’s Republic of China; 3Interventional Cancer Institute of Chinese Integrative Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China; 4Department of General Surgery, Institute of Fudan-Minhang Academic Health System, Minhang Hospital, Fudan University, Shanghai, People’s Republic of China*These authors contributed equally to this workCorrespondence: Wei LiDepartment of General Surgery, Putuo Hospital, Shanghai University of Traditional, Chinese Medicine, Shanghai, 200062, People’s Republic of ChinaEmail liwei1511972@163.comQiong LiDepartment of General Surgery, Institute of Fudan-Minhang Academic Health System, Minhang Hospital, Fudan University, Shanghai, 201100, People’s Republic of ChinaEmail 1030190686@qq.comPurpose: As rapidly dividing cells are usually the target of anticancer chemotherapy, it is inevitable that rapidly dividing normal cells become damaged, with myelosuppressive effects being a serious side effect of this therapy. Many recent studies have found that exosomal microRNAs (miRNAs) are related to the occurrence of some diseases.Patients and Methods: Small RNA sequencing was used to investigate differential exosomal miRNAs with the same expression trend between groups after chemotherapy: MildA (before chemotherapy in patients with mild myelosuppression) and MildB (after chemotherapy in patients with mild myelosuppression); SevereA (before chemotherapy in patients with severe myelosuppression) and SevereB (after chemotherapy in patients with severe myelosuppression). A Venn diagram was generated to screen exosomal miRNAs related to chemotherapy. Small RNA sequencing was also used to investigate differentially expressed exosomal miRNAs among these groups, and exosomal miRNAs related to myelosuppression after chemotherapy was explored using a Venn diagram. RT-qPCR was applied to further verify the sequencing results. We performed target gene prediction and functional analysis for candidate exosomal miRNAs.Results: Compared with that in the MildA or SevereA group, an increase in exosomal miR-122-5p was found in the MildB or SevereB group, and the expression level was lower in the SevereB group than in the MildB group. However, we found no notable difference in its expression level between the MildA and SevereA groups. Similar results were not obtained for the remaining miRNAs. RT-qPCR confirmed the screening results. Further analyses indicated that exosomal miR-122-5p targets CDK4 to inhibit the cell cycle.Conclusion: The expression level of exosomal miR-122-5p in the serum of patients with colorectal cancer correlates with the severity of myelosuppression caused by chemotherapy, and miR-122-5p targets CDK4 to inhibit cell cycle progression.Keywords: colorectal cancer, chemotherapy, myelosuppression, miR-122-5p

Jiadi Xing,* Maoxing Liu,* Kai Xu,* Pin Gao, Fei Tan, Zhendan Yao, Nan Zhang, Hong Yang, Chenghai Zhang, Ming Cui, Xiangqian Su Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Gastrointestinal Surgery IV, Peking University Cancer Hospital and Institute, Beijing 100142, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xiangqian Su KeyLaboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Gastrointestinal Surgery IV, Peking University Cancer Hospital and Institute, NO. 52 Fucheng Road, Haidian District, Beijing 100142, People’s Republic of ChinaTel +86-13801262916Email suxiangqian@bjmu.edu.cnBackground: Few studies have evaluated the outcomes of transhiatal and right thoracoabdominal resection of Siewert type II adenocarcinoma of the esophagogastric junction. This study investigated the relative effect of these two methods in the surgical treatment of Siewert type II adenocarcinoma of the esophagogastric junction.Methods: Clinical data for 211 Siewert type II cancer patients were collected and classified into transhiatal group (n = 181) and right thoracoabdominal group (n = 30) according to surgical approach. Short-term outcomes were compared between these two groups. A 1:1 propensity score matching was performed using a logistic regression model. Recurrence-free survival and overall survival were compared between the matched groups.Results: The right thoracoabdominal group had significantly greater intraoperative blood loss and longer operative time compared with transhiatal group. Complications corresponding to Clavien–Dindo grade III or higher were 4.4% in transhiatal group and 30% in right thoracoabdominal group (P < 0.05). The right thoracoabdominal group exhibited greater blood loss, longer operative time, longer hospitalization, and a smaller number of lymph nodes retrieved than the transhiatal group as evidenced by PSM analysis, and patients in transhiatal group also experienced significantly better survival than patients in right thoracoabdominal group.Conclusion: In this study, the transhiatal approach was associated with more favorable short-term and oncological outcomes than the right thoracoabdominal group approach for Siewert type II adenocarcinoma of the esophagogastric junction. The transhiatal approach with total gastrectomy appears to be an optional choice for this type of tumor, especially for esophagus invasion ≤ 2 cm. Well-designed randomized control trials are necessary to validate our findings.Keywords: adenocarcinoma of the esophagogastric junction, Siewert type II, transhiatal resection, right thoracoabdominal resection

Yanqiu Xu,1,* Xiaohui Fan,1,* Cai Sun,2 Lingling Yin,2 Tingting Qiu,2 Jieyun Xia,2 Xiaomin Zhong,3 Linyan Xu,1,4 Depeng Li,2 Zhenyu Li,1,2,4 Feng Zhu,1,2 Kailin Xu1,2,4 1Blood Disease Institute, Xuzhou Medical University, Xuzhou, Jiangsu 221002, People’s Republic of China; 2Department of Hematology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu 221002, People’s Republic of China; 3Department of Oncology, Affiliated Huai’an First People’s Hospital of Nanjing Medical University, Huai’an, Jiangsu Province 223300, People’s Republic of China; 4Key Laboratory of Bone Marrow Stem Cell, Xuzhou, Jiangsu Province 221002, People’s Republic of China*These authors contributed equally to this workCorrespondence: Feng ZhuDepartment of Hematology, The Affiliated Hospital of Xuzhou Medical University, 99, West Huaihai Road, Quanshan District, Xuzhou, Jiangsu 221002, People’s Republic of ChinaTel +86 516 8580 6985Fax +86 516 8580 1527Email frankfeng_2004@126.comBackground: Splenic diffuse red pulp small B-cell lymphoma (SDRPSBCL) is rare and accounts for less than 1% of non-Hodgkin’s lymphoma. As the first or accompanying symptoms of SDRPSBCL, gastrointestinal hemorrhage (GIH) is rather unusual.Patients and Methods: We reported on a patient with SDRPSBCL complicated with GIH. According to the enteroscopy, pathological sections of spleen and intestine, immunohistochemistry and other related laboratory examinations, the patient was diagnosed as SDRPSBCL (stage IVb) complicated with colon and rectal ulcers. The clinical manifestations were hematochezia, unformed stool, continuous anal pain and poor quality of life. Subsequently, the patient was treated by six cycles of CHOP (cyclophosphamide + doxorubicin + vincristine + hydroprednisone) regimens. The clinical features, diagnosis and treatment were analyzed retrospectively and the relevant literatures were reviewed.Results: After the first course of chemotherapy, the patient did not have any more bloody stool and the stool was shaped. After six cycles of chemotherapy, the patient’s anus was no longer painful and he has been in complete remission according to the result of positron emission tomography CT.Conclusion: Through analysis of this case, we could elucidate that after the primary disease was alleviated, the bleeding degree of digestive tract was relieved, which provided the basis for the clinical treatment of this rare disease.Keywords: splenic diffuse red pulp small B-cell lymphoma, gastrointestinal hemorrhage, symptom, diagnosis, chemotherapy

Yecai Huang,1,2 Mei Feng,1,2 Xuegang Yang,3 Jie Zhou,2 Lu Li,2 Ke Xu,2 Guohui Xu,1,3,* Jinyi Lang1,2,* 1School of Medicine, University of Electronic Science and Technology of China , Chengdu, People’s Republic of China; 2Department of Radiation Oncology, Sichuan Cancer Hospital and Institute, Sichuan Cancer Center, Radiation Oncology Key Laboratory of Sichuan Province, Chengdu, People’s Republic of China; 3Department of Interventional Radiology, Sichuan Cancer Hospital and Institute, Sichuan Cancer Center, Radiation Oncology Key Laboratory of Sichuan Province, Chengdu, People’s Republic of China*These authors contributed equally to this workCorrespondence: Guohui Xu; Jinyi LangSichuan Cancer Hospital& Institute, Sichuan Cancer Center, Radiation Oncology Key Laboratory of Sichuan Province, School of Medicine, University of Electronic Science and Technology of China, No. 55, South Renmin Road, Wuhou District, Chengdu 610000, People’s Republic of ChinaTel +86-28-85420152Email xgh0913@hotmail.com; langjy610@163.comBackground: Nasopharyngeal carcinoma (NPC) is one of the most highly radiosensitive malignancies; however, some locally advanced NPC patients experienced local recurrence even though they received aggressive treatment regimens. Defining the tumor volume precisely is important to escalate the total dose required for the primary tumor. In this study, we aimed to investigate the feasibility and efficacy of dose escalation guided by DW-MRI in patients with locally advanced NPC.Patients and Methods: A total of 230 patients with locally advanced NPC treated with intensive modulated radiotherapy (IMRT) at Sichuan Cancer Hospital between January 2010 and January 2015 were enrolled in this retrospective study. All the patients were treated with all-course of simultaneous integrated boost-IMRT. DW-MRI-guided dose escalation with 2.2– 2.5 Gy/F, qd for 1– 3 days or 1.2– 1.5 Gy/F, bid for 1– 3 days were prescribed to 123 patients. Survival and complication of the patients were evaluated, and multivariate analysis was performed.Results: The median follow-up of patients in the DW-MRI-guided dose-escalation group and the conventional group was 48 months (range 8– 88 months) and 52 months (range 6– 90 months), respectively. The 5-year overall survival rate, distant metastasis-free survival rate, progression-free survival, and local recurrence-free survival (LRFS) of patients in the dose-escalation group and the conventional group were 88% vs 82.5% (p = 0.244), 86.1% vs 83.3% (p = 0.741), 82.2% vs 76.6% (p = 0.286), and 89.1% vs 80.1% (p = 0.029), respectively. Multivariate analysis showed that dose escalation was independent prognostic factor for LRFS (HR 0.386, 95% CI 0.163– 0.909, p = 0.03).Conclusion: DW-MRI-guided dose escalation is a feasible strategy to improve local control of patients with locally advanced NPC. The treatment-related complications are tolerable.Keywords: nasopharyngeal carcinoma, DW-MRI, dose escalation, locally advanced

Jun Chang,1,2 Ling Hong,2 Yaozhong Liu,3 Yiwen Pan,2 Hao Yang,2 Wenrui Ye,3 Keli Xu,4 Zhijian Li,1 Shubing Zhang1,2,5,6 1Department of Anesthesiology, The Second Xiangya Hospital of Central South University, Changsha, Hunan 410011, People’s Republic of China; 2Department of Cell Biology, School of Life Sciences, Central South University, Changsha, Hunan 410013, People’s Republic of China; 3Xiangya Medical School, Central South University, Changsha, Hunan 410013, People’s Republic of China; 4Cancer Institute, University of Mississippi Medical Center, Jackson, MS 39216, USA; 5Hunan Key Laboratory of Animal Models for Human Diseases, Central South University, Changsha, Hunan 410013, People’s Republic of China; 6Breast Cancer Research Center, School of Life Sciences, Central South University, Changsha, Hunan 410013, People’s Republic of ChinaCorrespondence: Zhijian LiDepartment of Anesthesiology, The Second Xiangya Hospital of Central South University, Changsha, Hunan 410011, People’s Republic of ChinaTel +8613787314214Email lizhijian@csu.edu.cnShubing ZhangDepartment of Cell Biology, School of Life Sciences, Central South University, Changsha, Hunan 410013, People’s Republic of ChinaTel +861397589680Email shubingzhang@csu.edu.cnPurpose: Molecular targeting is a powerful approach for aggressive claudin-low breast cancer (CLBC). Overexpression of PI3K catalytic subunit gamma (PIK3CG) in human CLBC is offering a promising opportunity for targeted therapies. We utilized a specific inhibitor of PIK3CG combined with paclitaxel (PTX) to treat CLBC cells in vitro and in vivo.Patients and Methods: The tumor cells growth and apoptosis in vitro were analyzed by CCK8, plate clone formation assay, tumorsphere assay, Hoechst staining and flow cytometry. The invasion and metastasis ability of tumor cells in vitro were investigated by wound healing and transwell experiments. Critical gene expression levels were checked by qRT-PCR and Western blot. Xenograft models with CLBC cell lines in SCID mice were established to investigate the effect of combined drugs in vivo.Results: We identified that PIK3CG was a potential therapeutic target for CLBC patients. Targeting PIK3CG potentiated CLBC cells growth inhibition in 2D and 3D cultures by PTX. Inhibition of PIK3CG activation could enhance CLBC cells apoptosis and migration suppression induced by PTX. Manipulating autophagy was a validated approach for the use of PIK3CG inhibitor. Using CLBC xenograft mice model, we found that CLBC tumors in vivo could be well treated by combined drugs of PIK3CG inhibitor and PTX.Conclusion: We demonstrated that PIK3CG was a potential target for the therapy of CLBC and inhibition of PIK3CG activation could reinforce the therapeutic effect of this aggressive disease by PTX. The combined use of PIK3CG inhibitor and PTX might be a potential regimen for treating this subtype of breast cancer.Keywords: PIK3CG, paclitaxel, claudin-low breast cancer, combined drugs, targeted therapy

Yajun Wei,* Gang Wang,* Cheng Wang, Yangming Zhou, Jingcheng Zhang, Kai Xu Department of Biliary and Pancreatic Surgery, Anhui Provincial Hospital Affiliated with Anhui Medical University, Hefei, Anhui 230001, People’s Republic of China*These authors contributed equally to this workCorrespondence: Cheng WangDepartment of Biliary and Pancreatic Surgery, Anhui Provincial Hospital Affiliated with Anhui Medical University, No. 17 Lujiang Road, Hefei, Anhui Province 230001, People’s Republic of ChinaTel +86 51 62283292Fax +86 51 65327735Email shengyiwangcheng@126.comBackground: There is a growing number of evidence which report the relationship of the dual-specificity phosphatases 14 (DUSP14) with physiological and pathological mechanisms in the human body. However, it is still not known what if any role DUSP14 plays in pancreatic cancer.Materials and Methods: The study evaluates the levels of DUSP14 in the pancreatic cancer tissues and cell lines using Western blotting and qRT-PCR to assess the levels of the DUSP14 and epithelial–mesenchymal transition (EMT) biomarkers. After the DUSP14 was blocked, the following assays were performed: colony formation, assessments of scratch wound and transwell to examine the effects of DUSP14 on the proliferation, migration and invasion of the pancreatic cancer.Results: Results showed that there was a significant increase in the level of DUSP14 expression both in the pancreatic cancer tissues and cell lines. Experimental downregulation of DUSP14 induced the inhibition of the capacity of proliferation, migration and invasion of the pancreatic cancer cells. Western blotting analyses showed changes in the levels of expression of the EMT biomarkers, which helped to determine the function of DUSP14 in EMT.Conclusion: In conclusion, we suggest that DUSP14 is a novel molecular target that can be used for the treatment of pancreatic cancer.Keywords: pancreatic cancer, DUSP14, migration, invasion, epithelial-mesenchymal transition

Kehan Xu,1,* Jialin Li,1,* Mengzi Hu,2,* Hao Zhang,1 Jian Yang,1 Haiyi Gong,1 Bo Li,1 Wei Wan,1 Jianru Xiao1 1Department of Orthopedic Oncology, Changzheng Hospital, Second Military Medical University, Shanghai 200003, People’s Republic of China; 2Department of Orthopedics, Xuzhou Central Hospital, Xuzhou, Jiangsu 221009, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jianru Xiao; Wei Wan Email jianruxiao83@smmu.edu.cn; ggflyfish@126.comPurpose: The purpose of this retrospective study was to identify preoperative inflammatory biomarkers and clinical parameters and evaluate their prognostic significance in patients with spinal metastasis from clear cell renal cell carcinoma (CCRCC).Patients and methods: Correlations of overall survival (OS) with traditional clinical parameters and inflammatory indicators including the neutrophil–lymphocyte ratio (NLR), platelet–lymphocyte ratio (PLR), lymphocyte–monocyte ratio (LMR), albumin–globulin ratio (AGR), and C-reactive protein to albumin ratio (CRP/Alb ratio) were analyzed in 95 patients with spinal metastasis from CCRCA using the Kaplan–Meier method to identify potential prognostic factors. Factors with P values ≤ 0.1 were subjected to multivariate analysis by Cox regression analysis. P values ≤ 0.05 were considered statistically significant.Results: The 95 patients included in this study were followed up by a mean of 48.8 months (median 51 months; range 6–132 months), during which 21 patients died, with a death rate of 22.1%. The statistical results indicated that patients with total piecemeal spondylectomy (TPS), targeted therapy, NLR < 3.8 and PLR < 206.9 had a significantly longer OS rate.Conclusion: TPS and targeted therapy could significantly prolong the OS of patients with spinal metastasis from CCRCC. In addition, NLR and PLR are robust and convenient prognostic indicators that have a discriminatory ability superior to other inflammatory biomarkers.Keywords: clear cell renal cell carcinoma, spinal metastasis, overall survival, prognosis, inflammatory biomarkers

Haiyun Zhang,1,* Yujie Liu,2,* Kehan Xu,2,* Kai Mao,1 Weidong Han,1 Feifan Xu,1 Wei Wan,2 Yajun Sun3 1Department of Laboratory Medicine, The Sixth People’s Hospital of Nantong, Jiangsu 226000, People’s Republic of China; 2Department of Orthopedic Oncology, Changzheng Hospital, Second Military Medical University, Shanghai, 200003, People’s Republic of China; 3Department of Laboratory Medicine, The Fourth People’s Hospital of Nantong, Jiangsu 226000, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yajun Sun; Wei WanDepartment of Laboratory Medicine, The Fourth People’s Hospital of Nantong, Chenggang Road, Jiangsu 226000, People’s Republic of ChinaEmail yajun_sun1@163.com; wei_wan66@163.comIntroduction: Amphiphysin 1 (AMPH-1) is involved in endocytosis, and its expression is upregulated in osteosarcoma compared with osteofibrous dysplasia.Methods: We investigated the role of AMPH-1 in osteosarcoma cells via both gain-of-function and loss-of-function experiments.Results: Knockdown of AMPH-1 in osteosarcoma cells promoted cell cycle progression and cell proliferation and attenuated apoptosis. Notably, silencing AMPH-1 increased osteosarcoma progression in a mouse tumor model. The results obtained upon AMPH-1 knockdown and AMPH-1 overexpression indicates that AMPH-1 is involved in regulating MEK/ERK signaling.Conclusion: These data suggest that AMPH-1 plays an important role in osteosarcoma and may represent a novel therapeutic target for osteosarcoma treatment.Keywords: AMPH-1, osteosarcoma, ERK signaling pathway

Hui Ren,1,2,* Zhihui Chen,1,* Liang Yang,1,* Weixin Xiong,1 Hong Yang,3 Kaiwu Xu,1 Ertao Zhai,1 Li Ding,4 Yulong He,1,2 Xingming Song11Department of Gastrointestinal Surgery Centre, First Affiliated Hospital, Sun Yat-sen University, Guangzhou, People’s Republic of China; 2Center for Digestive Disease, Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, People’s Republic of China; 3Department of Operating Room, First Affiliated Hospital, Sun Yat-sen University, Guangzhou, People’s Republic of China; 4Department of Pathology, First Affiliated Hospital, Sun Yat-sen University, Guangzhou, People’s Republic of China*These authors contributed equally to this workAim: Identifying high-efficiency prognostic markers for colorectal cancer (CRC) is necessary for clinical practice. Increasing evidence demonstrates that apolipoprotein C1 (APOC1) promotes carcinogenesis in some human cancers. However, the expression status and biological function of APOC1 in CRC remain unclear.Materials and methods: We detected the association between APOC1 expression and clinicopathological features in 140 CRC patients by immunohistochemistry. Small interfering RNA (siRNA) technology was used to downregulate APOC1 expression in CRC cells. Cell proliferation was estimated by CCK8 and clonogenic assays. The cell cycle and apoptosis were analyzed by flow cytometry. Cell migration and invasion were examined by a transwell assay. Gene set enrichment analysis (GSEA) and protein expression of signaling pathways were used to suggest the possible APOC1-associated pathways in CRC.Results: APOC1 was highly expressed in CRC tissues. High immunohistochemistry (IHC) expression of APOC1 was correlated with the N stage, M stage and TNM stage. High IHC APOC1 expression in CRC tissues was associated with poor prognosis. Univariate and multivariate Cox regression analyses showed that APOC1 was an independent risk factor for OS. Cell proliferation of CRC cell lines was inhibited by the downregulation of APOC1. Moreover, si-APOC1 transfection induced cell cycle arrest but low apoptosis increases by regulating the expression of related proteins. Cell migration and invasion were also inhibited by the downregulation of APOC1. The Cancer Genome Atlas Colorectal Adenocarcinoma (TCGA COAD-READ) dataset analyzed by GSEA showed that APOC1 might be involved in the mitogen-activated protein kinase (MAPK) signaling pathway, which was further preliminarily confirmed by Western blotting.Conclusion: APOC1 was overexpressed in CRC tissues, and a high level of APOC1 contributed to a poor prognosis. APOC1 expression influenced the cell proliferation ability and motility capacity of CRC via the MAPK pathway. APOC1 could act as a novel prognostic biomarker in CRC.Keywords: apolipoprotein C1, APOC1, colorectal cancer, prognosis, MAPK signaling

Chunli Wu,1–3 Liang Yang,4 Xun Qi,2 Taifang Wang,3 Meng Li,3 Ke Xu1,2 1Department of Radiology, The First Affiliated Hospital of China Medical University, Shenyang, China; 2Key Laboratory of Diagnostic Imaging and Interventional Radiology of Liaoning Province, The First Affiliated Hospital of China Medical University, Shenyang, China; 3Department of Radiation Oncology, The Fourth Affiliated Hospital of China Medical University, Shenyang, China; 4Department of General Surgery, The Fourth Affiliated Hospital, China Medical University, Shenyang 110032, China Background: Resistance to radiation therapy is still a challenge for treatment of pancreatic cancer (PC). Long non-coding RNAs (lncRNA) HOTAIR has been found to play a oncogenic role in several cancers. However, the correlation between HOTAIR and radiotherapy in PC is still unclear.Methods: TCGA data was collected to analyze the expression of HOTAIR and its relationship with PC progression. A series of functional experiments were conducted to explore the role of HOTAIR in PC radiosensitivity and its underlying molecular mechanisms.Results: By the analysis of the TCGA data, we found HOTAIR expression in PC tissues was significantly higher than normal tissues and associated with tumor progression. The function analysis showed HOTAIR was enriched in biological regulation and response to stimulus.And in vitro study, the expression of HOTAIR was increased in PANC-1 and AsPC-1 cells after radiation. We identified that HOTAIR knockdown could enhance radiosensitivity and influence autophagy by up-regulating ATG7 expression in PC cells. By futher rescue experiments using rapamycin, activation of autophagy could reversed the the inhibition of cell proliferation and colony formation, as well as promotion of apoptosis mediated by HOTAIR knockdown, indicating that HOTAIR knockdown promoted radiosensitivity of PC cells by regulating autophagy. Conclusion: Our finding revealed the the regulatory role of HOTAIR in radiosensitivity and provided a a new sight to improve radiotherapy effciency in PC. Keywords: HOTAIR, pancreatic cancer, radiosensitivity, autophagy, Atg7

Xin Wang, Liming Xu, Zhenzhen Yin, Daquan Wang, Qi Wang, Kunpeng Xu, Jinlin Zhao, Lujun Zhao, Zhiyong Yuan, Ping Wang Department of Radiation Oncology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, Tianjin’s Clinical Research Center for Cancer, Key Laboratory of Breast Cancer, Prevention and Therapy, Tianjin Medical University, Ministry of Education, Tianjin, 300060, China Objective: In order to identify risk factors associated with locoregional recurrence (LRR) and assess the role of postmastectomy radiotherapy (PMRT) in early breast cancer (BC), managed with neoadjuvant chemotherapy (NAC) and mastectomy, a retrospective analysis of BC diagnosed with clinical stage T1-2N0-1 was conducted.Patients and methods: A total of 217 patients were included in this analysis. The median age was 50 years (24–72 years). The clinical stage distributions were cT1 in 15 cases, cT2 in 202, cN0 in 53, and cN1 in 161 cases. All patients were treated with NAC and mastectomy, and 128 patients received PMRT.Results: With a median follow-up time of 61 months, the 5-year cumulative LRR rate was 12%. Multivariate analysis demonstrated that pathological N stage, lymph-vascular invasion, and histological grade were independent prognostic factors associated with LRR. A nomogram model based on these factors was established, based on which the patients were deeply stratified into low- and high-risk group. In the low-risk group, radiotherapy did not decrease LRR (3.3% in PMRT group, 1.7% in no PMRT group, P=0.192). While in the high-risk group, PMRT significantly decreased LRR (21.8% in PMRT group, 42.2% in no PMRT group, P=0.031).Conclusion: Lymph-vascular invasion, histological grade, as well as pathological N stage were important prognostic factors associated with LRR in BC patients staged in cT1-2N0-1, who were managed with NAC and mastectomy. In our cohort, not only clinical and pathological stage information but also other risk factors were taken into consideration when adjuvant PMRT was recommended. In the high-risk subgroup, PMRT significantly improved the prognosis. Keywords: breast cancer, neoadjuvant chemotherapy, postmastectomy radiotherapy, prognosis

Bin Liu,1 Xiaojing Xing,1 Xiang Li,2 Qianxue Guo,1 Tonghong Xu,1 Ke Xu3 1Medical Oncology, Cancer Hospital of China Medical University, Liaoning Cancer Hospital and Institute, Shenyang, Liaoning Province, People’s Republic of China; 2Breast Surgery, Cancer Hospital of China Medical University, Liaoning Cancer Hospital and Institute, Shenyang, Liaoning Province, People’s Republic of China; 3Thoracic Surgery, Cancer Hospital of China Medical University, Liaoning Cancer Hospital and Institute, Shenyang, Liaoning Province, People’s Republic of China Purpose: Zinc finger protein 259 (ZNF259), also known as ZPR1, is a zinc finger-containing protein that can bind the intracellular tyrosine kinase domain of EGFR. At present, our knowledge on ZNF259 in cancers is limited. Here, we aimed to explore the biological functions of ZNF259 in breast cancer and reveal their mechanisms.Patients and methods: The expression of ZNF259 was measured in 133 cases of breast cancer by immunohistochemistry. The online database Kaplan–Meier (KM) Plotter Online Tool was used to analyze the relationship between ZNF259 expression and breast cancer patient survival prognosis. Plasmid transfection and small interfering RNA and inhibitor treatments were carried out to explore the functions of ZNF259 in breast cancer cell lines and its potential mechanism. Matrigel invasion and wound healing assays were performed to detect the invasion and migration ability of cancer cells. In addition, protein expressions in tissues and cells were determined by Western blotting.Results: ZNF259 expression was much higher in breast cancer cells than in the adjacent normal breast duct glandular epithelial cells (75.94% vs 7.52%, P

Ke Xu,1 Bin Liu,2 Yegang Ma,1 Baojin Xu,3 Xiaojing Xing1 1Department of Thoracic Surgery, Cancer Hospital of China Medical University, Shenyang, Liaoning Province, People’s Republic of China; 2Department of Medical Oncology, Cancer Hospital of China Medical University, Shenyang, Liaoning Province, People’s Republic of China; 3General Surgery Liaoning Cancer Hospital and Institute, Shenyang, Liaoning Province, People’s Republic of China Purpose: Zinc finger SWIM-type containing 5 (ZSWIM5) is a newly discovered protein, which contains a novel zinc-chelating domain SWIM (CxCxnCxH), and is predicted to interact with DNA or proteins. Currently, the knowledge of functions of ZSWIM5 remains limited. In this study, we aimed to elucidate the biological functions of ZSWIM5 and their mechanisms.Patients and methods: We detected the expression of ZSWIM5 in samples from 139 cases of non-small-cell lung cancer (NSCLC) patients and six cell lines using immunohistochemistry and Western blot. Moreover, we explored the biological functions of ZSWIM5 in lung cancer cells by siRNA interference and cDNA transfection of ZSWIM5.Results: The results showed that compared with adjacent non-tumor lung tissues, ZSWIM5 expression was significantly decreased in NSCLC tissues (P=0.0199) and that the ZSWIM5-positive rate in non-tumor tissues (76.67%) was notably higher than that in NSCLC tissues (40.29%). ZSWIM5 expression in human normal bronchial epithelial cells was also much higher than that in lung cancer lines (P