Reduced stratifin expression can serve as an independent prognostic factor for poor survival in patients with esophageal squamous cell carcinoma.
Stratifin plays an important role in cancer biology by interfering with intracellular signalling pathways and cell-cycle checkpoints. Decreased expression of stratifin gene has been reported to be a poor prognostic indicator in a variety of human malignant tumors.


OBJECTIVE
To clarify the role and prognostic significance of stratifin in esophageal squamous cell carcinoma (ESCC).


METHODS
The alteration of stratifin messenger RNA (mRNA) and protein was analyzed by reverse-transcription and quantitative real-time polymerase chain reaction (QRT-PCR) and Western blotting in 20 paired ESCC and nonneoplastic esophageal mucosa tissues, respectively. Then, immunohistochemistry (IHC) was used to evaluate expression of stratifin in tissues of 148 ESCC patients (including the former 20 pairs of tissues) and correlate it with clinicopathological parameters and prognosis of ESCC patients.


RESULTS
The stratifin level of mRNA and protein was markedly downregulated in ESCC tissue compared with in corresponding nonneoplastic esophageal epithelium (P<0.05). Similarly, the positive rate of stratifin protein expression was lower in the esophageal cancer than in paired nonneoplastic esophageal epithelium as detected by IHC (P=0.007). Statistically, the downregulation of stratifin expression was correlated with tumor infiltration depth (P=0.003), lymph node metastasis (P=0.008), distant metastasis (P=0.013), and lymphovascular invasion (P=0.007) of ESCC. Furthermore, the reduced stratifin expression was associated with shorter 5-year survival rate of ESCC patients after curative surgery (P<0.0001). On the basis of univariate and multivariate Cox regression analysis, we found that reduced stratifin expression, T4 stage, lymph node metastasis, and distant metastasis were independent risk factors for worse prognosis in ESCC patients.


CONCLUSIONS
The present report indicates that stratifin could be a useful indicator for prognosis of this disease, as well as a potential target for more effective therapy.
Ren
Hong-Zheng
HZ
Department of Pathology, Xiangya Basic Medical College, Central South University, Changsha, China.
Pan
Guo-qing
GQ
Wang
Jin-Sheng
JS
Wen
Ji-Fang
JF
Wang
Kuan-Song
KS
Luo
Geng-Qiu
GQ
Shan
Xu-zheng
XZ
D048948:14-3-3 Proteins / Q000032:analysis* / Q000235:genetics; D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis* / Q000235:genetics; D015153:Blotting, Western; D002294:Carcinoma, Squamous Cell / Q000737:chemistry* / Q000235:genetics / Q000401:mortality / Q000556:secondary / Q000601:surgery; D016009:Chi-Square Distribution; D015536:Down-Regulation; D004938:Esophageal Neoplasms / Q000737:chemistry* / Q000235:genetics / Q000401:mortality / Q000473:pathology / Q000601:surgery; D016629:Esophagectomy; D005092:Exonucleases / Q000032:analysis* / Q000235:genetics; D005095:Exoribonucleases; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D011237:Predictive Value of Tests; D016016:Proportional Hazards Models; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018570:Risk Assessment; D012307:Risk Factors; D013997:Time Factors; D016896:Treatment Outcome
D048948:14-3-3 Proteins; D014408:Biomarkers, Tumor; D012333:RNA, Messenger; D005092:Exonucleases; D005095:Exoribonucleases; C413442:SFN protein, human