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Yuan Xue,1,2,* Pei-Dong Li,1,2,* Xue-Mei Tang,3,* Zai-Hua Yan,1,2 Shu-Sen Xia,1 Hong-Peng Tian,1 Zuo-Liang Liu,1 Tong Zhou,1 Xue-Gui Tang,4 Guang-Jun Zhang1,2 1The Second Department of Gastrointestinal Surgery, The Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan, People’s Republic of China; 2Institute of Hepatobiliary, Pancreatic and Intestinal Disease, North Sichuan Medical College, Nanchong, Sichuan, People’s Republic of China; 3Department of Ultrasound, The Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan, People’s Republic of China; 4Anorectal Department of Integrated Traditional Chinese and Western Medicine, The Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xue-Gui TangAnorectal Department of Integrated Traditional Chinese and Western Medicine, The Affiliated Hospital of North Sichuan Medical College, 63 Wenhua Road, Nanchong 637000, Sichuan, People’s Republic of ChinaTel +86 817 2262419Email txg668nc@sohu.comGuang-Jun ZhangThe Second Department of Gastrointestinal Surgery, The Affiliated Hospital of North Sichuan Medical College, 63 Wenhua Road, Nanchong 637000, Sichuan, People’s Republic of ChinaTel +86 817 2262419Email zhanggj1977@126.comPurpose: Colorectal cancer (CRC) is one of the most common malignancies in the world. The prognosis of advanced CRC is still poor. The purpose of this study was to identify a gene expression profile associated with CRC that may contribute to the early diagnosis of CRC and improve patient prognosis.Patients and Methods: Five pairs of CRC tissues and paracancerous tissues were used to identify causative genes using microarray assays. The prognostic value of Cytochrome C Oxidase Assembly Factor 1 Homolog (COA1) in CRC was assessed in 90 CRC patients. Loss-of-function assays, cell proliferation assays using Celigo and MTT, colony formation assays, a subcutaneous xenograft mouse model, and apoptosis assays were used to define the effects of downregulation of COA1 in CRC cells in vitro and in vivo. The underlying molecular mechanisms of COA1 in CRC were also investigated.Results: The causative gene COA1 was identified through microarray analysis. COA1 expression in CRC was notably associated with pathologic differentiation, tumor size, and tumor depth. COA1 expression may act as an independent prognostic factor for overall survival of CRC. Knockdown of COA1 inhibited the proliferation of CRC cells in vitro and the tumorigenicity of CRC cells in vivo. Decreased COA1 expression induced apoptosis of CRC cells. Based on the microarray assay results comparing HCT116 cells transfected with lentivirus encoding anti-COA1 shRNA or negative control shRNA, ingenuity pathway analysis (IPA) revealed that the PI3K/AKT signaling pathway was significantly enriched. Moreover, CCND1, mTOR, AKT1, and MDM2 were identified as the downstream genes of COA1.Conclusion: These findings demonstrate that COA1 promotes CRC cell proliferation and inhibits apoptosis by regulating the PI3K/AKT signaling pathway. Our results implicate COA1 as a potential oncogene involved in tumor growth and progression of CRC.Keywords: colorectal cancer, COA1, proliferation, apoptosis, PI3K/AKT signaling

Xue-miao Tang,1,2,* Hao Chen,2,3,* Qing Li,1,2 Yiling Song,2,3 Shuping Zhang,2,3 Xiao-Shuan Xu,4 Yiwei Xu,5,6 Shulin Chen2,3 1Department of Ultrasound and Electrocardiogram, 2State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, 3Department of Clinical Laboratory, Sun Yat-Sen University Cancer Center, Guangzhou, 4School of Laboratory Medicine, Guangdong Medical University, 5Department of Clinical Laboratory, The Cancer Hospital of Shantou University Medical College, 6The Key Laboratory of Molecular Biology for High Cancer Incidence Coastal Chaoshan Area, Shantou University Medical College, Guangdong, China *These authors contributed equally to this work Objective: The cardiac safety of cetuximab and panitumumab, particularly as single agents, has not been investigated extensively. This trial was designed to specifically evaluate the cardiac safety of cetuximab and panitumumab as single therapy in Chinese chemotherapy-refractory metastatic colorectal cancer (mCRC) patients.Patients and methods: Sixty-one patients received cetuximab at an initial dose of 400 mg/m2 intravenously over 120 minutes on day 1 (week 1), followed by a maintenance dose of 250 mg/m2 intravenously over 60 minutes on day 1 of each 7-day cycle. Forty-three patients received panitumumab at a dose of 6 mg/kg intravenously every 14 days. Routine laboratory tests and electrocardiogram (ECG) were performed at baseline, during therapy and after the treatment (4th and 10th months). The incidence of elevation of troponin I ultra (TNI Ultra), abnormal ECGs, cardiac events and noncardiac adverse events (AEs) were recorded and analyzed.Results: The incidence of elevation of TNI Ultra between the two groups had no significance (p=0.681), and TNI Ultra+ was observed more frequently in patients with metastases to more than three organs and they received fourth or above lines of chemotherapy. The most frequent abnormal ECG manifestations were nonspecific ST changes and QTc prolongation in the two groups. At 10 months after treatment, most of the abnormal ECG manifestations were reversed. The most common cardiac AEs of cetuximab and panitumumab included palpitations, dyspnea, chest pain and arrhythmias requiring treatment. Most of the events were mild and transient. The incidence of cardiac AEs had no significant difference between the two groups. Rash was still the most common noncardiac AE in both groups.Conclusion: Cetuximab and panitumumab showed favorable cardiac safety as single agents for Chinese chemotherapy-refractory mCRC patients. But monitoring for cardiac AEs is still necessary throughout the entire treatment process. Keywords: cetuximab, panitumumab, targeted therapy, colorectal cancer, toxicity, cardiac safety