Decreased expression of semaphorin 3D is associated with genesis and development in colorectal cancer.
BACKGROUND
Semaphorin 3D (SEMA3D) plays important roles in the genesis and progress of many cancers. However, the relationship between SEMA3D and colorectal cancer (CRC) remains unknown. The aim of this study was to investigate whether SEMA3D can be used as a predictive marker for the diagnosis, metastasis, and prognosis of CRC by assessing the expression of SEMA3D in the tissues and serum of CRC patients.


METHODS
Real-time quantitative polymerase chain reaction (qPCR) was used to measure the expression of SEMA3D mRNA in 100 CRC tissues and matched normal tissues. qPCR was also used to detect the expression of SEMA3D mRNA in the CRC cell line RKO. RKO cells were transfected with SEMA3D small-interring RNA (siRNA) to interfere with endogenous SEMA3D. The migratory ability of control and SEMA3D siRNA-transfected RKO cells was determined by transwell assays. Enzyme-linked immunosorbent assay (ELISA) was utilized to detect the levels of SEMA3D in the serum of 80 CRC patients and 100 normal healthy controls. The expression of SEMA3D in 215 CRC tissues was assessed using immunohistochemistry (IHC). Then, statistical analyses were adopted to assess SEMA3D protein levels and clinical pathological characteristics.


RESULTS
The mRNA expression of SEMA3D was significantly lower in CRC tissues than in paired normal tissues (t = 5.027, P < 0.0001). Compared with normal healthy controls, the serum levels of SEMA3D were decreased significantly in CRC patients (t = 3.656, P = 0.0003). The expression of SEMA3D protein was linked to lymph node metastasis, and low expression led to lymph node metastasis (χ2= 8.415, P = 0.004). The expression of SEMA3D in CRC tissues was a favorable prognostic factor. Patients with a higher expression of SEMA3D experienced longer survival (P = 0.002, log-rank [Mantel-Cox]; Kaplan-Meier). In addition, multivariate Cox's proportional hazard model revealed that SEMA3D is an independent prognostic marker (hazard ratio [HR] 1.818, 95% CI 1.063-3.110, P = 0.029). Moreover, transwell assays showed that knocking down SEMA3D significantly increased RKO cell migration (t = 9.268, P = 0.0008).


CONCLUSIONS
SEMA3D might function as a tumor suppressor during the formation and development of CRC. SEMA3D might become a predictive marker for the diagnosis, metastasis, and prognosis of CRC and provide a novel target for the prevention and treatment of CRC.
Department of Pathology, The First Hospital of Jiaxing, Zhejiang, People's Republic of China.
Zhen
Z
Wang
The Criminal Investigation Detachment of Jiaxing Public Security Bureau, Zhejiang, People's Republic of China.
Meiman
M
Ding
Department of Pathology, The First Hospital of Jiaxing, Zhejiang, People's Republic of China.
Naiying
N
Qian
Department of Pathology, The First Hospital of Jiaxing, Zhejiang, People's Republic of China.
Beifeng
B
Song
Department of Pathology, The First Hospital of Jiaxing, Zhejiang, People's Republic of China.
Jiayin
J
Yu
Department of Pathology, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, People's Republic of China.
Jinlong
J
Tang
Department of Pathology, The First Hospital of Jiaxing, Zhejiang, People's Republic of China. 11018140@zju.edu.cn.
Jingyu
J
Wang
D017209:Apoptosis; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D016022:Case-Control Studies; D002465:Cell Movement; D049109:Cell Proliferation; D015179:Colorectal Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D005260:Female; D005500:Follow-Up Studies; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D039961:Semaphorins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D014408:Biomarkers, Tumor; D012333:RNA, Messenger; D034741:RNA, Small Interfering; C000592402:Sema3D protein, human; D039961:Semaphorins
Colorectal cancer; Metastasis; Prognosis; SEMA3D