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IntroductionCellular senescence is a cellular response to stress, including the activation of oncogenes, and is characterized by irreversible proliferation arrest. Restricted studies have provided a relationship between cellular senescence and immunotherapy for esophageal cancer.MethodsIn the present study, we obtained clinical sample of colon cancer from the TCGA database and cellular senescence-related genes from MSigDB and Genecard datasets. Cellular senescence-related prognostic genes were identified by WGCNA, COX, and lasso regression analysis, and a cellular senescence-related risk score (CSRS) was calculated. We constructed a prognostic model based on CSRS. Validation was performed with an independent cohort that GSE53625. Three scoring systems for immuno-infiltration analysis were performed, namely ssGSEA analysis, ESTIMATE scores and TIDE scores.ResultFive cellular senescence-related genes, including H3C1, IGFBP1, MT1E, SOX5 and CDHR4 and used to calculate risk score. Multivariate regression analysis using cox regression model showed that cellular senescence-related risk scores (HR=2.440, 95% CI=1.154-5.159, p=0.019) and pathological stage (HR=2.423, 95% CI=1.119-5.249, p=0.025) were associated with overall survival (OS). The nomogram model predicts better clinical benefit than the American Joint Committee on Cancer (AJCC) staging for prognosis of patients with esophageal cancer with a five-year AUC of 0.946. Patients with high CSRS had a poor prognosis (HR=2.93, 95%CI=1.74-4.94, pDiscussionIn summary, our study suggested that CSRS is a prognostic risk factor for esophageal cancer. Patients with high CSRS may have worse immunotherapy outcomes.

Additional file 1: Table S1. Primer Sequence.

Supplemental material, sj-docx-1-tam-10.1177_17588359211023290 for Development and external validation of a novel nomogram for screening Chinese Lynch syndrome: based on a multicenter, population study by Mengyuan Yang, Dan Li, Wu Jiang, Lizhen Zhu, Haixing Ju, Yan Sun, Yuqiang Shan, Chunkang Yang, Jian Dong, Lin Wang, Baoping Wu, Meng Qiu, Xianli Yin, Xicheng Wang, Bin Xiong, Wei Yan, Tao Liu, Chenglin Liu, Xinru Mao, Kefeng Ding, Suzhan Zhang, Shu Zheng, Dong Xu, Peirong Ding and Ying Yuan in Therapeutic Advances in Medical Oncology

Xinyu Li,1,* Wen Chen,2,* Jing Jia,1,* Zhicheng You,3 Changjin Hu,4 Yihuang Zhuang,1 Zhibin Lin,1 Yan Liu,1 Chunkang Yang,5 Rongyu Xu1 1Quanzhou First Hospital, Quanzhou, Fujian Province, People’s Republic of China; 2The Second Affiliated Hospital of Fujian Medical University, Quanzhou, Fujian Province, People’s Republic of China; 3Yongchun County Hospital, Quanzhou, Fujian Province, People’s Republic of China; 4Jinjiang Hospital of Traditional Chinese Medicine Affiliated to Fujian University of Traditional Chinese Medicine, Jinjiang, Fujian Province, People’s Republic of China; 5Fujian Tumor Hospital, Fuzhou, Fujian Province, People’s Republic of China*These authors contributed equally to this workCorrespondence: Chunkang YangDepartment of Gastroenterology, Fujian Tumor Hospital, Fuzhou, Fujian Province, People’s Republic of ChinaEmail chunyangy03@163.comRongyu XuDepartment of Surgical Oncology, Quanzhou First Hospital, Quanzhou, Fujian Province, People’s Republic of ChinaEmail xry641127@sina.comBackground: Long non-coding RNA regulator of reprogramming (LINC-RoR) has shown different expressions in a variety of tumors as a stem cell inducer through reprogramming regulation. However, its role and regulation mechanisms in colorectal cancer (CRC) are still unclear.Materials and Methods: Quantitative real-time PCR and Western blot were performed to examine LINC-RoR expression in paired CRC samples and cell lines. The relationship of LINC-RoR expression with clinicopathological characteristics and clinical outcomes was analyzed. The biological functions of LINC-RoR were studied by MTS and colony formation in vitro. Cell apoptosis was analysed by the flow cytometry. The Dual-luciferase reporter assays and RIP assays were performed to explore the regulatory relationship of LINC-RoR.Results: In this study, we found that LINC-RoR was upregulated in CRC cell lines and tissues. High expression of LINC-RoR was associated with poorer survival time and multivariate analysis results showed that LINC-RoR was an independent risk factor of tumor malignancy progression. Overexpression of LINC-RoR promoted the cell proliferation and knocked down it can reverse the effect in vitro. The regulatory network of LINC-ROR/miR-6833-3p/SMC4 was predicted with bioinformatics analysis tools and validated via dual-luciferase reporter assays and RIP. Further study revealed that in overexpression LINC-RoR cell lines the expression of miR-6833-3p was downregulated and miR-6833-3p can inhibit its target gene SMC4, the apoptosis-related protein.Conclusion: We concluded that LINC-RoR functions as an oncogene in CRC through the miR-6833-3p/SMC4 pathway.Keywords: LINC-RoR, colorectal cancer, miR-6833-3p, SMC4, non-coding RNA, apoptosis

Yanxia Sun,*,1,2 Xiaolan Lai,*,3 Yue Yu,1,2 Jieyu Li,2,4 Lei Cao,3 Wansong Lin,2,4 Chuanzhong Huang,2,4 Jinrong Liao,2,4 Wei Chen,1,2 Chao Li,5 Chunkang Yang,6 Mingang Ying,6 Qiang Chen,3 Yunbin Ye2,41School of Basic Medical Sciences, Fujian Medical University, Fuzhou 350122, Fujian Province, People’s Republic of China; 2Laboratory of Immuno-Oncology, Fujian Provincial Cancer Hospital, Fuzhou 350014, Fujian Province, People’s Republic of China; 3Department of Medical Oncology, Union Hospital of Fujian Medical University, Fuzhou 350001, Fujian Province, People’s Republic of China; 4Fujian Key Laboratory of Translational Cancer Medicine, Fuzhou 350014, Fujian Province, People’s Republic of China; 5Department of Pathology, Fujian Provincial Cancer Hospital, Fuzhou 350014, Fujian Province, People’s Republic of China; 6Department of Abdominal Surgery, Fujian Provincial Cancer Hospital, Fuzhou 350014, Fujian Province, People’s Republic of China*These authors contributed equally to this workBackground: Inhibitor of DNA binding 1 (Id1) is upregulated in multiple cancers, and Id1overexpression correlates with cancer aggressiveness and poor clinical outcomes in cancer patients. However, its roles in cancer stem-like cells (CSCs) and epithelial-mesenchymal transition (EMT) are still elusive.Purpose: This study aimed to examine the role of Id1 on the mediation of CRC stemness and explore the underlying mechanisms.Methods: Id1 and CD133 expression was detected by qPCR assay and immunohistochemistry (IHC) in normal mucosal and primary colorectal cancer (CRC) specimens. Id1 was stably knocked down (KD) in human CRC cell lines. Spheres forming assay and tumorigenic assay were performed to evaluate self-renewal capacity and tumor initiation. Expression of CSC- and EMT-related markers and TCF/LEF activity were assessed in HCT116 cells after Id1KD.Results: qPCR assay showed higher Id1 and CD133 expression in CRC specimens than in normal mucosal specimens (P