Effects of JWA, XRCC1 and BRCA1 mRNA expression on molecular staging for personalized therapy in patients with advanced esophageal squamous cell carcinoma.
BACKGROUND
DNA damage repair genes JWA, XRCC1 and BRCA1 were associated with clinical outcomes and could convert the response to the cisplatin-based therapy in some carcinomas. The synergistic effects of JWA, XRCC1 and BRCA1 mRNA expression on personalized therapy remain unknown in advanced esophageal squamous cell carcinoma (ESCC).


METHODS
We employed quantitative real-time polymerase chain reaction (qPCR) to determine the expression of JWA, XRCC1 and BRCA1 mRNA in paraffin-embedded specimen from 172 patients with advanced ESCC who underwent the first-line cisplatin-or docetaxel-based treatments.


RESULTS
High JWA or XRCC1mRNA expression was correlated with longer median overall survival (mOS) in all the patients (both P<0.001) or in subgroups with different regimens (all P<0.05), but not correlated with response rate (RR, all P>0.05). Multivariate analysis revealed that high JWA (HR 0.22; 95% CI 0.13-0.37; P<0.001) or XRCC1 (HR 0.36; 95% CI 0.21-0.63; P<0.001) mRNA expression emerged as the independent prognostic factors for ESCC patients in this cohort. But no significant difference in prognostic efficacy was found between JWA plus XRCC1 and JWA alone through ROC analysis. Further subgroup analysis showed cisplatin-based treatments could improve mOS of patients with low JWA expression (P<0.05), especially in those with low BRCA1 expression simultaneously (P<0.001); while in patients with high JWA expression, high BRCA1 mRNA expression was correlated with increased mOS in docetaxel-based treatments (P=0.044).


CONCLUSIONS
JWA, XRCC1and BRCA1 mRNA expression could be used as predictive markers in molecular staging for personalized therapy in patients with advanced ESCC who received first-line cisplatin- or docetaxel-based treatments.
Department of Medical Oncology, Huai'an First People's Hospital, Nanjing Medical University, Huai'an, 223300, China. wb_934@163.com.
Bin
B
Wei
Department of Medical Oncology, Huai'an First People's Hospital, Nanjing Medical University, Huai'an, 223300, China. kxrshq2014@163.com.
Qin
Q
Han
Department of Medical Oncology, Huai'an First People's Hospital, Nanjing Medical University, Huai'an, 223300, China. wu89128@126.com.
Lijuan
L
Xu
Department of Medical Oncology, Huai'an First People's Hospital, Nanjing Medical University, Huai'an, 223300, China. njmuzxh@163.com.
Xiaohui
X
Zhang
Department of Medical Oncology, Huai'an First People's Hospital, Nanjing Medical University, Huai'an, 223300, China. zhujinghuaian@sina.com.
Jing
J
Zhu
Department of Medical Oncology, Huai'an First People's Hospital, Nanjing Medical University, Huai'an, 223300, China. wanlimeilissa@163.com.
Li
L
Wan
Department of Medical Oncology, Huai'an First People's Hospital, Nanjing Medical University, Huai'an, 223300, China. jinyan_05170422@163.com.
Yan
Y
Jin
Department of Medical Oncology, Huai'an First People's Hospital, Nanjing Medical University, Huai'an, 223300, China. qzy09010625@sina.cn.
Zhaoye
Z
Qian
Department of Medical Oncology, Huai'an First People's Hospital, Nanjing Medical University, Huai'an, 223300, China. wjj891208@163.com.
Jingjing
J
Wu
Department of Medical Oncology, Huai'an First People's Hospital, Nanjing Medical University, Huai'an, 223300, China. hayy_gy@163.com.
Yong
Y
Gao
Department of Molecular Cell Biology and Toxicology, Jiangsu Key Lab of Cancer Biomarkers, Prevention & Treatment Cancer Center; School of Public Health, Nanjing Medical University, Nanjing, 210029, China. jwzhou@njmu.edu.cn.
Jianwei
J
Zhou
Department of Medical Oncology, Huai'an First People's Hospital, Nanjing Medical University, Huai'an, 223300, China. hayycxf@163.com.
Xiaofei
X
Chen
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D019313:BRCA1 Protein / Q000235:genetics*; D014408:Biomarkers, Tumor / Q000235:genetics; D002294:Carcinoma, Squamous Cell / Q000737:chemistry / Q000188:drug therapy* / Q000235:genetics; D002945:Cisplatin / Q000008:administration & dosage; D004268:DNA-Binding Proteins / Q000235:genetics*; D000077143:Docetaxel; D004938:Esophageal Neoplasms / Q000737:chemistry / Q000188:drug therapy* / Q000235:genetics*; D005260:Female; D015870:Gene Expression; D006360:Heat-Shock Proteins / Q000235:genetics*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics*; D008297:Male; D026901:Membrane Transport Proteins; D008875:Middle Aged; D057285:Precision Medicine; D011379:Prognosis; D012333:RNA, Messenger / Q000032:analysis*; D012372:ROC Curve; D066066:Response Evaluation Criteria in Solid Tumors; D015996:Survival Rate; D043823:Taxoids / Q000008:administration & dosage; D000076105:X-ray Repair Cross Complementing Protein 1
C484566:ARL6IP5 protein, human; D019313:BRCA1 Protein; D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; D006360:Heat-Shock Proteins; D047908:Intracellular Signaling Peptides and Proteins; D026901:Membrane Transport Proteins; D012333:RNA, Messenger; D043823:Taxoids; D000076105:X-ray Repair Cross Complementing Protein 1; C000619371:XRCC1 protein, human; D000077143:Docetaxel; D002945:Cisplatin