Elevated expression of ASCL2 is an independent prognostic indicator in lung squamous cell carcinoma.
OBJECTIVE
ASCL2, a basic helix-loop-helix (bHLH) transcription factor, is putatively involved in tumour progression. This study aimed to evaluate ASCL2 expression level in non-small-cell carcinoma (NSCLC) and assess its prognostic value for patients.


METHODS
ASCL2 protein expression was detected by immunohistochemistry (IHC cohort) in 79 cases of squamous cell carcinoma (SCC) and 67 cases of adenocarcinoma (AC). Kaplan-Meier analysis and Cox regression analysis were performed to evaluate the prognostic significance of ASCL2. The same analyses were conducted in a cohort (n=790) from The Cancer Genome Atlas database (TCGA) to validate the expression pattern and prognostic value of ASCL2.


RESULTS
ASCL2 expression levels were significantly increased in SCC compared with normal lung tissue (p<0.001) and AC (p=0.008). High ASCL2 expression was associated with advanced tumour-node-metastasis (TNM) stage (p=0.023) and worse differentiation status (p=0.001) in SCC, but a positive correlation between ASCL2 expression level and advanced TNM stage (p=0.016) was observed in AC. Kaplan-Meier analysis showed that ASCL2 was prognostic in SCC (p=0.004) but not in AC (p=0.183). Multivariable Cox regression analysis indicated that elevated expression of ASCL2 was an independent prognostic factor (HR 2.764; p=0.030) in SCC patients. The expression pattern and prognostic significance of ASCL2 in SCC and AC were validated using the TCGA cohort.


CONCLUSIONS
Elevated expression of ASCL2 may identify an aggressive subgroup in SCC and serve as an independent prognostic indicator in these patients.
Institute of Pathology and Southwest Cancer Center, Southwest Hospital, Third Military Medical University, Chongqing, China Key Laboratory of Tumor Immunopathology of Ministry of Education of China, Third Military Medical University, Chongqing, China.
Xu-Gang
XG
Hu
Institute of Pathology and Southwest Cancer Center, Southwest Hospital, Third Military Medical University, Chongqing, China Key Laboratory of Tumor Immunopathology of Ministry of Education of China, Third Military Medical University, Chongqing, China.
Lu
L
Chen
Institute of Pathology and Southwest Cancer Center, Southwest Hospital, Third Military Medical University, Chongqing, China Key Laboratory of Tumor Immunopathology of Ministry of Education of China, Third Military Medical University, Chongqing, China.
Qing-liang
QL
Wang
Institute of Pathology and Southwest Cancer Center, Southwest Hospital, Third Military Medical University, Chongqing, China Key Laboratory of Tumor Immunopathology of Ministry of Education of China, Third Military Medical University, Chongqing, China.
Xi-long
XL
Zhao
Institute of Pathology and Southwest Cancer Center, Southwest Hospital, Third Military Medical University, Chongqing, China Key Laboratory of Tumor Immunopathology of Ministry of Education of China, Third Military Medical University, Chongqing, China.
Juan
J
Tan
Institute of Pathology and Southwest Cancer Center, Southwest Hospital, Third Military Medical University, Chongqing, China Key Laboratory of Tumor Immunopathology of Ministry of Education of China, Third Military Medical University, Chongqing, China.
You-hong
YH
Cui
Institute of Pathology and Southwest Cancer Center, Southwest Hospital, Third Military Medical University, Chongqing, China Key Laboratory of Tumor Immunopathology of Ministry of Education of China, Third Military Medical University, Chongqing, China.
Xin-dong
XD
Liu
Institute of Pathology and Southwest Cancer Center, Southwest Hospital, Third Military Medical University, Chongqing, China Key Laboratory of Tumor Immunopathology of Ministry of Education of China, Third Military Medical University, Chongqing, China.
Xia
X
Zhang
Institute of Pathology and Southwest Cancer Center, Southwest Hospital, Third Military Medical University, Chongqing, China Key Laboratory of Tumor Immunopathology of Ministry of Education of China, Third Military Medical University, Chongqing, China.
Xiu-Wu
XW
Bian
D000230:Adenocarcinoma / Q000401:mortality / Q000473:pathology; D000328:Adult; D000368:Aged; D051792:Basic Helix-Loop-Helix Proteins / Q000032:analysis / Q000096:biosynthesis*; D014408:Biomarkers, Tumor / Q000032:analysis*; D002294:Carcinoma, Squamous Cell / Q000401:mortality / Q000473:pathology*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000401:mortality / Q000473:pathology*; D008297:Male; D011379:Prognosis; D016016:Proportional Hazards Models; D046888:Tissue Array Analysis
D051792:Basic Helix-Loop-Helix Proteins; D014408:Biomarkers, Tumor; C065501:ASCL2 protein, human
CANCER RESEARCH; HISTOPATHOLOGY; LUNG CANCER