PMID- 37172522
OWN - NLM
STAT- MEDLINE
DCOM- 20230526
LR  - 20230526
IS  - 1618-0631 (Electronic)
IS  - 0344-0338 (Linking)
VI  - 246
DP  - 2023 Jun
TI  - lncRNA NORAD, soluble ICAM1 and their correlations may be related to the 
      regulation of the tumor immune microenvironment in laryngeal squamous cell 
      carcinoma (LSCC).
PG  - 154494
LID - S0344-0338(23)00194-2 [pii]
LID - 10.1016/j.prp.2023.154494 [doi]
AB  - NORAD, non-coding RNA activated by DNA damage, is a Long non-coding RNA (lncRNA) 
      transcript that modulates genome stability and has been reported to be 
      dysregulated in different cancers. Although it has been reported to be 
      upregulated in tumor cells mostly for solid organ cancers, it has also been 
      reported to be downregulated in some cancers. Although the pathophysiological 
      mechanism is not fully understood, a negative correlation between NORAD and 
      intercellular cell adhesion molecule-1 (ICAM-1) has been shown in experimental 
      models, but this situation has not been evaluated in terms of cancer. We aimed to 
      evaluate the potential roles of these two biomarker candidates together and 
      separately in the clinicopathological axis in Laryngeal squamous cell carcinoma 
      (LSCC) in a case-control study setting. The interactions of NORAD and ICAM1 at 
      the RNA level were evaluated interactively by the RIblast program. sICAM1 
      (soluble intercellular cell adhesion molecule-1) levels were determined by ELISA 
      in one hundred and five individuals (forty-four LSCC, sixty-one control) and 
      lncRNA NORAD expression in eighty-eight tissues (forty-four LSCC tumors, 
      forty-four tumor-free surrounding tissues) was determined by Real-time PCR. While 
      the energy treesholud was - 16 kcal/mol between NORAD and ICAM1, the total energy 
      was 176.33 kcal/mol, and 9 base pair pairings from 4 critical points were 
      detected. NORAD expression level was found to be higher in tumor surrounding 
      tissue compared to tumor tissue, and sICAM1 was higher in the control group 
      compared to LSCC (p = 0.004; p = 0.02). NORAD discreminte tumor surrounding 
      tissue from tumor (AUC: 0.674; optimal sensitivity:87.50%; optimal specificity 
      54.55%; cut-off point as >1.58 fold change; P = 0.034). The sICAM1 level was 
      found to be higher in the control (494,814 +/- 93.64 ng/L) than LSCC 
      (432.95 +/- 93.64 ng/L) (p = 0.02). sICAM1 discreminte control group from LSCC 
      (AUC: 0.624; optimal sensitivity 68,85%; optimal specificity 61,36%; cut-off 
      point </=115,0 ng/L; (p = 0.033). A very strong negative correlation was found 
      between NORAD expression and patients' sICAM1 levels (r = -.967; n = 44; 
      p = 0.033). sICAM1 levels were found to be 1.63 times higher in NORAD 
      downregulated subjects compared to upregulated ones (p = 0.031). NORAD was 3.63 
      times higher in those with alcohol use, and sICAM 1 was 5.77 times higher in 
      those without distant organ metastasis (p = 0.043; 0.004). The increased NORAD 
      expression in the tumor microenvironment in LSCC, the activation of T cells via 
      TCR signaling, and the decrease of sICAM in the control group in correlation with 
      NORAD suggests that ICAM1 may be needed as a membrane protein in the tumor 
      microenvironment. NORAD and ICAM1 may be functionally related to tumor 
      microenvironment and immune control in LSCC.
CI  - Copyright (c) 2023 Elsevier GmbH. All rights reserved.
FAU - Horozoglu, Cem
AU  - Horozoglu C
AD  - Faculty of Medicine, Halic University, Istanbul, Turkey.
FAU - Bal, Gorkem
AU  - Bal G
AD  - Faculty of Medicine, Istanbul University, Istanbul, Turkey.
FAU - Kabadayi, Batuhan
AU  - Kabadayi B
AD  - Faculty of Medicine, Istanbul University, Istanbul, Turkey.
FAU - Hakan, Mehmet Tolgahan
AU  - Hakan MT
AD  - Department of Molecular Medicine, Aziz Sancar Institute of Experimental Medicine, 
      Istanbul University, Istanbul, Turkey.
FAU - Sonmez, Dilara
AU  - Sonmez D
AD  - Department of Molecular Medicine, Aziz Sancar Institute of Experimental Medicine, 
      Istanbul University, Istanbul, Turkey.
FAU - Nacarkahya, Gulper
AU  - Nacarkahya G
AD  - Department of Medical Biology, Faculty of Medicine, Gaziantep University, 
      Gaziantep, Turkey.
FAU - Verim, Aysegul
AU  - Verim A
AD  - Department of Otorhinolaryngology/Head and Neck Surgery, Haydarpasa Numune 
      Education and Research Hospital, Istanbul, Turkey.
FAU - Yaylim, Ilhan
AU  - Yaylim I
AD  - Department of Molecular Medicine, Aziz Sancar Institute of Experimental Medicine, 
      Istanbul University, Istanbul, Turkey. Electronic address: ilhanyaylim@gmail.com.
LA  - eng
PT  - Journal Article
DEP - 20230429
PL  - Germany
TA  - Pathol Res Pract
JT  - Pathology, research and practice
JID - 7806109
RN  - 0 (Cell Adhesion Molecule-1)
RN  - 0 (ICAM1 protein, human)
RN  - 126547-89-5 (Intercellular Adhesion Molecule-1)
RN  - 0 (MicroRNAs)
RN  - 0 (RNA, Long Noncoding)
RN  - 0 (NORAD long non-coding RNA, human)
SB  - IM
MH  - Humans
MH  - *Carcinoma, Squamous Cell/pathology
MH  - Case-Control Studies
MH  - Cell Adhesion Molecule-1/metabolism
MH  - Cell Line, Tumor
MH  - Cell Proliferation
MH  - Gene Expression Regulation, Neoplastic
MH  - *Head and Neck Neoplasms/genetics
MH  - Intercellular Adhesion Molecule-1/metabolism
MH  - *Laryngeal Neoplasms/pathology
MH  - *MicroRNAs/genetics
MH  - *RNA, Long Noncoding/genetics
MH  - Squamous Cell Carcinoma of Head and Neck/genetics
MH  - Tumor Microenvironment
OTO - NOTNLM
OT  - LSCC
OT  - LncRNA
OT  - NORAD
OT  - SICAM1
OT  - Tumor immune microenvironment
COIS- Declaration of Competing Interest The authors declare that they have no known 
      competing financial interests or personal relationships that could have appeared 
      to influence the work reported in this paper.
EDAT- 2023/05/13 15:13
MHDA- 2023/05/25 06:42
CRDT- 2023/05/12 18:08
PHST- 2023/02/20 00:00 [received]
PHST- 2023/03/28 00:00 [revised]
PHST- 2023/04/28 00:00 [accepted]
PHST- 2023/05/25 06:42 [medline]
PHST- 2023/05/13 15:13 [pubmed]
PHST- 2023/05/12 18:08 [entrez]
AID - S0344-0338(23)00194-2 [pii]
AID - 10.1016/j.prp.2023.154494 [doi]
PST - ppublish
SO  - Pathol Res Pract. 2023 Jun;246:154494. doi: 10.1016/j.prp.2023.154494. Epub 2023 
      Apr 29.