PMID- 37201466 OWN - NLM STAT- MEDLINE DCOM- 20230615 LR - 20230615 IS - 1618-0631 (Electronic) IS - 0344-0338 (Linking) VI - 247 DP - 2023 Jul TI - Clinicopathological value of hematopoietic cell kinase overexpression in laryngeal squamous cell carcinoma tissues. PG - 154534 LID - S0344-0338(23)00234-0 [pii] LID - 10.1016/j.prp.2023.154534 [doi] AB - Laryngeal squamous cell carcinoma (LSCC) is the most lethal cancer in head and neck tumors. Although hematopoietic cell kinase (HCK) has been proven to be an oncogene in several solid tumors, its roles in LSCC remain obscure. This is the first study to evaluate the clinical value of HCK in LSCC, with the aim of exploring its expression status and potential molecular mechanisms underlying LSCC. LSCC tissue-derived gene chips and RNA-seq data were collected for a quantitive integration of HCK mRNA expression level. To confirm the protein expression level of HCK, a total of 82 LSCC tissue specimens and 56 non-tumor laryngeal epithelial controls were collected for in-house tissue microarrays and immunohistochemical staining. Kaplan-Meier curves were generated to determine the ability of HCK in predicting overall survival, progress-free survival, and disease-free survival of LSCC patients. LSCC overexpressed genes and HCK co-expressed genes were intersected to preliminarily explore the enriched signaling pathways of HCK. It was noticed that HCK mRNA was markedly overexpressed in 323 LSCC tissues compared with 196 non-LSCC controls (standardized mean difference = 0.81, p < 0.0001). Upregulated HCK mRNA displayed a moderate discriminatory ability between LSCC tissues and non-tumor laryngeal epithelial controls (area under the curve = 0.78, sensitivity = 0.76, specificity = 0.68). The higher expression level of HCK mRNA could predict worse overall survival and disease-free survival for LSCC patients (p = 0.041 and p = 0.013). Lastly, upregulated co-expression genes of HCK were significantly enriched in leukocyte cell-cell adhesion, secretory granule membrane, and extracellular matrix structural constituent. Immune-related pathways were the predominantly activated signals, such as cytokine-cytokine receptor interaction, Th17 cell differentiation, and Toll-like receptor signaling pathway. In conclusion, HCK was upregulated in LSCC tissues and could be utilized as a risk predictor. HCK may promote the development of LSCC by disturbing immune signaling pathways. CI - Copyright (c) 2023 The Authors. Published by Elsevier GmbH.. All rights reserved. FAU - Xia, Shuang AU - Xia S AD - Department of Human Anatomy, Guangxi Medical University, 22 Shuangyong Road, Nanning, Guangxi, Zhuang Autonomous Region 530021, PR China. FAU - Li, Jian-Di AU - Li JD AD - Department of Pathology, First Affiliated Hospital of Guangxi Medical University, 6 Shuangyong Road, Nanning, Guangxi, Zhuang Autonomous Region 530021, PR China. FAU - Yan, Shi-Bai AU - Yan SB AD - Department of Pathology, First Affiliated Hospital of Guangxi Medical University, 6 Shuangyong Road, Nanning, Guangxi, Zhuang Autonomous Region 530021, PR China. FAU - Huang, Zhi-Guang AU - Huang ZG AD - Department of Pathology, First Affiliated Hospital of Guangxi Medical University, 6 Shuangyong Road, Nanning, Guangxi, Zhuang Autonomous Region 530021, PR China. FAU - Liu, Zhi-Su AU - Liu ZS AD - Department of Pathology, First Affiliated Hospital of Guangxi Medical University, 6 Shuangyong Road, Nanning, Guangxi, Zhuang Autonomous Region 530021, PR China. FAU - Jing, Shu-Wen AU - Jing SW AD - Department of Pathology, First Affiliated Hospital of Guangxi Medical University, 6 Shuangyong Road, Nanning, Guangxi, Zhuang Autonomous Region 530021, PR China. FAU - Li, Da-Zhi AU - Li DZ AD - Department of Pathology, First Affiliated Hospital of Guangxi Medical University, 6 Shuangyong Road, Nanning, Guangxi, Zhuang Autonomous Region 530021, PR China. FAU - Song, Chang AU - Song C AD - Department of Pathology, First Affiliated Hospital of Guangxi Medical University, 6 Shuangyong Road, Nanning, Guangxi, Zhuang Autonomous Region 530021, PR China. FAU - Chen, Yi AU - Chen Y AD - Department of Pathology, First Affiliated Hospital of Guangxi Medical University, 6 Shuangyong Road, Nanning, Guangxi, Zhuang Autonomous Region 530021, PR China. FAU - Wang, Li-Ting AU - Wang LT AD - Department of Pathology, First Affiliated Hospital of Guangxi Medical University, 6 Shuangyong Road, Nanning, Guangxi, Zhuang Autonomous Region 530021, PR China. FAU - Zhou, Yu-Hong AU - Zhou YH AD - Department of Pathology, First Affiliated Hospital of Guangxi Medical University, 6 Shuangyong Road, Nanning, Guangxi, Zhuang Autonomous Region 530021, PR China. FAU - Huang, Rong AU - Huang R AD - Department of Human Anatomy, Guangxi Medical University, 22 Shuangyong Road, Nanning, Guangxi, Zhuang Autonomous Region 530021, PR China. FAU - Shi, Nan AU - Shi N AD - Department of Otorhinolaryngology-Head and Neck Surgery, First Affiliated Hospital of Guangxi Medical University, 6 Shuangyong Road, Nanning, Guangxi, Zhuang Autonomous Region 530021, PR China. FAU - Lan, Song-Yao AU - Lan SY AD - Department of Human Anatomy, Guangxi Medical University, 22 Shuangyong Road, Nanning, Guangxi, Zhuang Autonomous Region 530021, PR China. FAU - Chen, Gang AU - Chen G AD - Department of Pathology, First Affiliated Hospital of Guangxi Medical University, 6 Shuangyong Road, Nanning, Guangxi, Zhuang Autonomous Region 530021, PR China. FAU - Fan, Xiao-Hui AU - Fan XH AD - Department of Immunology and Microbiology, Guangxi Medical University, 22 Shuangyong Road, Nanning, Guangxi, Zhuang Autonomous Region 530021, PR China. Electronic address: fanxiaohui63@163.com. LA - eng PT - Journal Article DEP - 20230512 PL - Germany TA - Pathol Res Pract JT - Pathology, research and practice JID - 7806109 RN - EC 2.7.10.2 (Proto-Oncogene Proteins c-hck) RN - 0 (RNA, Messenger) SB - IM MH - Humans MH - Gene Expression Regulation, Neoplastic/genetics MH - *Laryngeal Neoplasms/genetics/pathology MH - Prognosis MH - Proto-Oncogene Proteins c-hck/genetics/metabolism MH - RNA, Messenger/genetics MH - *Squamous Cell Carcinoma of Head and Neck/genetics/pathology OTO - NOTNLM OT - Clinicopathological significance OT - Co-expression genes OT - Hematopoietic cell kinase OT - Laryngeal squamous cell carcinoma COIS- Declaration of Competing Interest None. EDAT- 2023/05/19 01:04 MHDA- 2023/06/12 06:42 CRDT- 2023/05/18 18:09 PHST- 2022/11/21 00:00 [received] PHST- 2023/03/26 00:00 [revised] PHST- 2023/05/11 00:00 [accepted] PHST- 2023/06/12 06:42 [medline] PHST- 2023/05/19 01:04 [pubmed] PHST- 2023/05/18 18:09 [entrez] AID - S0344-0338(23)00234-0 [pii] AID - 10.1016/j.prp.2023.154534 [doi] PST - ppublish SO - Pathol Res Pract. 2023 Jul;247:154534. doi: 10.1016/j.prp.2023.154534. Epub 2023 May 12.