Loss of LKB1 Protein Expression Correlates with Increased Risk of Recurrence and Death in Patients with Resected, Stage II or III Colon Cancer

Autor: Sardar Alam, Maria Trypaki, Dimitris Mavroudis, Vassilis Georgoulias, John Souglakos, Odysseas Zoras, Ippokratis Messaritakis, Maria Tzardi, Maria Sfakianaki, Chara Papadaki, Eleni Lagoudaki
Rok vydání: 2019
Předmět:
Male
0301 basic medicine
Cancer Research
Colorectal cancer
ΚRAS
medicine.disease_cause
Gastroenterology
0302 clinical medicine
AMP-Activated Protein Kinase Kinases
Stage (cooking)
Hazard ratio
Middle Aged
Prognosis
DNA-Binding Proteins
Oxaliplatin
Reverse transcription polymerase chain reaction
Treatment Outcome
Oncology
Chemotherapy
Adjuvant
Stage II-III
030220 oncology & carcinogenesis
Colonic Neoplasms
Immunohistochemistry
Original Article
Female
KRAS
medicine.drug
Adult
Proto-Oncogene Proteins B-raf
medicine.medical_specialty
LKB1
Down-Regulation
Protein Serine-Threonine Kinases
BRAF
Proto-Oncogene Proteins c-myc
Proto-Oncogene Proteins p21(ras)
03 medical and health sciences
Internal medicine
medicine
Humans
MSI
Adaptor Proteins
Signal Transducing
Aged
Neoplasm Staging
business.industry
Endonucleases
medicine.disease
Survival Analysis
Pyrimidines
030104 developmental biology
Mutation
ERCC1
business
Zdroj: Cancer Research and Treatment : Official Journal of Korean Cancer Association
ISSN: 2005-9256
1598-2998
DOI: 10.4143/crt.2019.008
Popis: Purpose The purpose of this study was to investigate the prognostic significance of liver kinase b1 (LKB1) loss in patients with operable colon cancer (CC). Materials and Methods Two hundred sixty-two specimens from consecutive patients with stage III or high-risk stage II CC, who underwent surgical resection with curative intent and received adjuvant chemotherapy with fluoropyrimidine and oxaliplatin, were analyzed for LKB1 protein expression loss, by immunohistochemistry as well as for KRAS exon 2 and BRAFV600E mutations by Sanger sequencing and TS, ERCC1, MYC, and NEDD9 mRNA expression by real-time quantitative reverse transcription polymerase chain reaction. Results LKB1 expression loss was observed in 117 patients (44.7%) patients and correlated with right-sided located primaries (p=0.032), and pericolic lymph nodes involvement (p=0.003), BRAFV600E mutations (p=0.024), and TS mRNA expression (p=0.041). Patients with LKB1 expression loss experienced significantly lower disease-free survival (DFS) (hazard ratio [HR], 1.287; 95% confidence interval [CI], 1.093 to 1.654; p=0.021) and overall survival (OS) (HR, 1.541; 95% CI, 1.197 to 1.932; p=0.002), compared to patients with LKB1 expressing expressing tumors. Multivariate analysis revealed LKB1 expression loss as independent prognostic factor for both decreased DFS (HR, 1.217; 95% CI, 1.074 to 1.812; p=0.034) and decreased OS (HR, 1.467; 95% CI, 1.226 to 2.122; p=0.019). Conclusion Loss of tumoral LKB1 protein expression, constitutes an adverse prognostic factor in patients with operable CC.
Databáze: OpenAIRE
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