PMID- 36007395
OWN - NLM
STAT- Publisher
LR  - 20231019
IS  - 1618-0631 (Electronic)
IS  - 0344-0338 (Linking)
VI  - 238
DP  - 2022 Oct
TI  - Expression and prognostic analysis of CLDN18 and Claudin18.2 in lung 
      adenocarcinoma.
PG  - 154068
LID - S0344-0338(22)00312-0 [pii]
LID - 10.1016/j.prp.2022.154068 [doi]
AB  - BACKGROUND: CLDN encodes a member of the claudin family. Claudin is a tight 
      junction protein that is mainly involved in cell migration. Claudin family is of 
      interest as a potential therapeutic target. Claudin18.2 is one of its important 
      isoforms and is mainly expressed in the stomach. Its expression and prognosis in 
      lung adenocarcinoma remain unknown. The aim of this study was to investigate the 
      correlation between CLDN18 and claudin18.2 expression and prognosis in lung 
      adenocarcinoma. METHODS: Two cohorts were introduced in this study: one from The 
      Cancer Genome Atlas (TCGA) CLDN18 mRNA public data (TCGA-LUAD, N = 551); the 
      other from 1079 cases of lung adenocarcinoma diagnosed at the Fourth Hospital of 
      Hebei Medical University, China, with immunohistochemical (IHC) detection of 
      claudin18.2 in tissue microarrays. the IHC-positive cases were again verified by 
      fluorescence in situ hybridization (FISH). RESULTS: The mRNA expression of CLDN18 
      was significantly lower in lung adenocarcinoma tissues than in normal lung 
      tissues (P < 0.05). Among 1079 Chinese lung adenocarcinoma cases, the overall 
      positive rate of IHC for Claudin18.2 was 7.78% (84/1079). Among those positive 
      for IHC, the positive rate of FISH was 11.9% (10/84), which accounted for 0.9% of 
      the total number of cases (10/1079). To explore the best scoring scheme for 
      Claudin 18.2, we used a four-group (IHC4) and two-group (IHC2) scoring method for 
      evaluation. We found that IHC4 better explained Claudin 18.2 expression and 
      helped us to find specific differences in clinical factors for weak, moderate and 
      strong Claudin 18.2 expression. This difference was not discernible in the IHC2 
      score. By survival analysis, we found that Claudin 18.2 (IHC4) was able to 
      stratify the prognosis of lung adenocarcinoma patients, with strongly positive 
      patients having a better prognosis than the other subgroups (p < 0.05). We also 
      found that patients with EGFR wild type or PD-L1 < 1% accompanied by strong 
      positive claudin18.2 had a significantly better prognosis than other subgroups 
      (P < 0.05). CONCLUSION: Claudin18.2 (IHC4) better reveals the clinical and 
      prognostic characteristics of patients with lung adenocarcinoma. Patients with 
      EGFR wild type and PD-L1 < 1% have a better prognosis and partially overlap with 
      claudin18.2 expression, so claudin18.2 may also be an important biomarker for 
      lung adenocarcinoma testing, which is particularly important for EGFR wild type 
      and PD-L1 < 1%.
CI  - Copyright (c) 2022. Published by Elsevier GmbH.
FAU - Liu, Junying
AU  - Liu J
AD  - Department of pathology, The Fourth Affiliated Hospital of Hebei Medical 
      University, No. 12, Jiankang Road, Shijiazhuang 050011, PR China.
FAU - Yang, Huichai
AU  - Yang H
AD  - Department of pathology, The Fourth Affiliated Hospital of Hebei Medical 
      University, No. 12, Jiankang Road, Shijiazhuang 050011, PR China.
FAU - Yin, Danjing
AU  - Yin D
AD  - Department of pathology, The Fourth Affiliated Hospital of Hebei Medical 
      University, No. 12, Jiankang Road, Shijiazhuang 050011, PR China.
FAU - Jia, Ying
AU  - Jia Y
AD  - Department of pathology, The Fourth Affiliated Hospital of Hebei Medical 
      University, No. 12, Jiankang Road, Shijiazhuang 050011, PR China.
FAU - Li, Shi
AU  - Li S
AD  - Department of pathology, The Fourth Affiliated Hospital of Hebei Medical 
      University, No. 12, Jiankang Road, Shijiazhuang 050011, PR China.
FAU - Liu, Yueping
AU  - Liu Y
AD  - Department of pathology, The Fourth Affiliated Hospital of Hebei Medical 
      University, No. 12, Jiankang Road, Shijiazhuang 050011, PR China. Electronic 
      address: annama@163.com.
LA  - eng
PT  - Journal Article
DEP - 20220810
PL  - Germany
TA  - Pathol Res Pract
JT  - Pathology, research and practice
JID - 7806109
SB  - IM
OTO - NOTNLM
OT  - Adenocarcinoma
OT  - CLDN18
OT  - Claudin18.2
OT  - Lung
OT  - Prognosis
COIS- Conflict of Interest This manuscript entitled " Expression and prognostic 
      analysis of CLDN18 and Claudin18.2 in lung adenocarcinoma" describes original 
      work that has not been considered for publication in any other journal. All 
      authors approved the manuscript and the submission of this report. There are no 
      conflicts of interest.
EDAT- 2022/08/26 06:00
MHDA- 2022/08/26 06:00
CRDT- 2022/08/25 18:24
PHST- 2022/05/09 00:00 [received]
PHST- 2022/08/04 00:00 [revised]
PHST- 2022/08/07 00:00 [accepted]
PHST- 2022/08/26 06:00 [pubmed]
PHST- 2022/08/26 06:00 [medline]
PHST- 2022/08/25 18:24 [entrez]
AID - S0344-0338(22)00312-0 [pii]
AID - 10.1016/j.prp.2022.154068 [doi]
PST - ppublish
SO  - Pathol Res Pract. 2022 Oct;238:154068. doi: 10.1016/j.prp.2022.154068. Epub 2022 
      Aug 10.