PMID- 35016744
OWN - NLM
STAT- MEDLINE
DCOM- 20220505
LR  - 20220716
IS  - 1555-3906 (Electronic)
IS  - 0965-0407 (Print)
IS  - 0965-0407 (Linking)
VI  - 29
IP  - 1
DP  - 2022 May 4
TI  - STAT3 Polymorphism Associates With mTOR Inhibitor-Induced Interstitial Lung 
      Disease in Patients With Renal Cell Carcinoma.
PG  - 11-23
LID - 10.3727/096504022X16418911579334 [doi]
AB  - We evaluated the association of signal transducer and activator of transcription 
      3 (STAT3) polymorphisms with the incidence of mammalian target of rapamycin 
      (mTOR) inhibitor-induced interstitial lung disease (ILD) in patients with renal 
      cell carcinoma (RCC). We also used lung-derived cell lines to investigate the 
      mechanisms of this association. Japanese patients with metastatic RCC who were 
      treated with mTOR inhibitors were genotyped for the STAT3 polymorphism, rs4796793 
      (1697C/G). We evaluated the association of the STAT3 genotype with the incidence 
      of ILD and therapeutic outcome. In the 57 patients included in the primary 
      analysis, the ILD rate within 140 days was significantly higher in patients with 
      the GG genotype compared with those with other genotypes (77.8% vs. 23.1%, odds 
      ratio=11.67, 95% confidential interval=3.0644.46). There were no significant 
      differences in progression-free survival or time-to-treatment failure between the 
      patients with the GG genotype and those with other genotypes. An in vitro study 
      demonstrated that some lung-derived cell lines carrying the GG genotype exhibited 
      an increase in the expression of mesenchymal markers, such as fibronectin, 
      N-cadherin, and vimentin, and decreases in E-cadherin, which is an epithelial 
      marker associated with exposure to everolimus, although STAT3 expression and 
      activity were not related to the genotype. In conclusion, the GG genotype of the 
      STAT3 rs4796793 polymorphism increases the risk of mTOR inhibitor-induced ILD, 
      supporting its use as a predictive marker for RCC.
FAU - Yamamoto, Kazuhiro
AU  - Yamamoto K
AD  - Department of Pharmacy, Kobe University HospitalKobeJapan.
FAU - Ioroi, Takeshi
AU  - Ioroi T
AD  - Department of Pharmacy, Kobe University HospitalKobeJapan.
FAU - Shinomiya, Kazuaki
AU  - Shinomiya K
AD  - Department of Pharmaceutical Care and Clinical Pharmacy, Faculty of 
      Pharmaceutical Sciences, Tokushima Bunri UniversityTokushimaJapan.
FAU - Yoshida, Ayaka
AU  - Yoshida A
AD  - Department of Pharmacy, Kobe University HospitalKobeJapan.
FAU - Harada, Kenichi
AU  - Harada K
AD  - Division of Urology, Kobe University Graduate School of MedicineKobeJapan.
FAU - Fujisawa, Masato
AU  - Fujisawa M
AD  - Division of Urology, Kobe University Graduate School of MedicineKobeJapan.
FAU - Omura, Tomohiro
AU  - Omura T
AD  - Department of Pharmacy, Kobe University HospitalKobeJapan.
FAU - Ikemi, Yasuaki
AU  - Ikemi Y
AD  - Department of Clinical Pharmacology and Therapeutics, Kyoto University 
      HospitalKyotoJapan.
FAU - Nakagawa, Shunsaku
AU  - Nakagawa S
AD  - Department of Clinical Pharmacology and Therapeutics, Kyoto University 
      HospitalKyotoJapan.
FAU - Yonezawa, Atsushi
AU  - Yonezawa A
AD  - Department of Clinical Pharmacology and Therapeutics, Kyoto University 
      HospitalKyotoJapan.
FAU - Ogawa, Osamu
AU  - Ogawa O
AD  - Department of Urology, Graduate School of Medicine, Kyoto UniversityKyotoJapan.
FAU - Matsubara, Kazuo
AU  - Matsubara K
AD  - Department of Clinical Pharmacology and Therapeutics, Kyoto University 
      HospitalKyotoJapan.
FAU - Iwamoto, Takuya
AU  - Iwamoto T
AD  - Department of Pharmacy, Mie University HospitalMieJapan.
FAU - Nishikawa, Kohei
AU  - Nishikawa K
AD  - Department of Nephro-Urologic Surgery and Andrology, Mie University Graduate 
      School of MedicineMieJapan.
FAU - Hayashi, Sayaka
AU  - Hayashi S
AD  - Department of Pharmacy, Kumamoto University HospitalKumamotoJapan.
FAU - Tohara, Daichi
AU  - Tohara D
AD  - Department of Pharmacy, Kumamoto University HospitalKumamotoJapan.
FAU - Murakami, Yoji
AU  - Murakami Y
AD  - Department of Urology, Graduate School of Medical Sciences, Kumamoto 
      UniversityKumamotoJapan.
FAU - Motoshima, Takanobu
AU  - Motoshima T
AD  - Department of Urology, Graduate School of Medical Sciences, Kumamoto 
      UniversityKumamotoJapan.
FAU - Jono, Hirofumi
AU  - Jono H
AD  - Department of Pharmacy, Kumamoto University HospitalKumamotoJapan.
FAU - Yano, Ikuko
AU  - Yano I
AD  - Department of Pharmacy, Kobe University HospitalKobeJapan.
LA  - eng
PT  - Journal Article
DEP - 20220111
PL  - United States
TA  - Oncol Res
JT  - Oncology research
JID - 9208097
RN  - 0 (MTOR Inhibitors)
RN  - 0 (STAT3 Transcription Factor)
RN  - 0 (STAT3 protein, human)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
SB  - IM
MH  - *Carcinoma, Renal Cell/drug therapy/genetics
MH  - Female
MH  - Humans
MH  - *Kidney Neoplasms/drug therapy/genetics/pathology
MH  - *Lung Diseases, Interstitial/chemically induced/drug therapy/genetics
MH  - MTOR Inhibitors
MH  - Male
MH  - Polymorphism, Single Nucleotide
MH  - STAT3 Transcription Factor/genetics
MH  - TOR Serine-Threonine Kinases/genetics
PMC - PMC9110706
COIS- The authors declare no conflicts of interest.
EDAT- 2022/01/13 06:00
MHDA- 2022/05/06 06:00
PMCR- 2022/05/04
CRDT- 2022/01/12 05:44
PHST- 2022/01/13 06:00 [pubmed]
PHST- 2022/05/06 06:00 [medline]
PHST- 2022/01/12 05:44 [entrez]
PHST- 2022/05/04 00:00 [pmc-release]
AID - OR1477 [pii]
AID - 10.3727/096504022X16418911579334 [doi]
PST - ppublish
SO  - Oncol Res. 2022 May 4;29(1):11-23. doi: 10.3727/096504022X16418911579334. Epub 
      2022 Jan 11.