Laryngeal squamous cell carcinoma (LSCC) is a common tumor of the head and neck, and accounts for 5% of all systemic malignant tumors [
1]. Early stage glottic LSCC has favorable prognosis (5-year survival rate, > 70%), whereas the prognosis of supraglottic and subglottic LSCC is poor because of late stage at diagnosis (5-year survival rate, < 50%) [
2]. The poor prognosis of LSCC is mainly attributed to lymphatic metastasis [
3]. Lymphatic metastasis is an important prognostic indicator for patients with LSCC. Distant metastasis frequently develops in late-stage LSCC, including stages 3, 4a, and 4b [
4]. Patients with head and neck squamous cell carcinoma (SCC) without node metastasis exhibited better prognosis than those with node metastasis, and more than 40% SCC of all cases of SCC with node metastasis were accompanied with recurrent and distant metastases [
5]. Therefore, prevention of lymphatic metastasis has become a hot topic in the treatment of LSCC.
KAI1 is a metastasis suppressor gene belonging to the transmembrane 4 superfamily. KAI1 regulates cell movement, metastasis, and proliferation by regulating cell adhesion [
6]. The low expression of KAI1 induces malignant transformation and tumor progression, leading to lymphatic metastasis and poor survival [
7‐
9]. Downregulation of KAI1 expression is closely related with carcinogenesis and metastasis of lower gingival SCC [
7], whereas KAI1 overexpression inhibits lymphangiogenesis and lymph node metastasis of pancreatic tumors [
10]. Given the important role of KAI1 in tumorgenesis, development, invasion, and metastasis, KAI1 may be used as a molecular marker for determining invasiveness, metastasis, and prognosis of LSCC [
11,
12]. nm23 is also an important suppressor gene associated with the metastatic potential of tumor [
13]. nm23 has antimetastatic function in normal cell growth; thus, its low expression may contribute to metastasis and poor prognosis among various tumors, including breast cancer, ovarian cancer, liver cancer, stomach carcinomas, and melanomas [
14]. Low nm23 expression was associated with lymph node and liver metastases in gastric cancer [
15]. LSCC patients with low nm23 expression exhibited significantly shorter survival than those with high nm23 expression [
16]. High nm23 expression is associated with favorable prognosis and may be used to evaluate the risk of recurrence in laryngeal carcinoma [
17,
18]. Although KAI1 and nm23 are closely related with tumor metastasis, their specific roles in lymphangiogenesis and lymphatic metastasis of LSCC still need to be studied.
Recently, various factors have been revealed to be closely related with lymphatic metastasis of LSCC, such as Notch 2 [
19], TRPP 2 [
20], EZH 2 [
21], MMP 9 [
22], and DNRG 3 [
23]. Because KAI1 and nm23 can influence tumor metastasis, we suspect that KAI1 and nm23 can be used as molecular markers in determining the lymphatic metastasis potential of LSCC. In this study, the expression of KAI1 and nm23 was detected in LSCC, and its relations with micro-lymphatic vessel density (MLVD) were investigated. The relations between KAI1 and nm23 expression and clinical characteristics of LSCC were evaluated. Our findings may identify the specific roles of KAI1 and nm23 in lymphangiogenesis and lymph metastasis of LSCC, which may provide valuable evidence for the clinical diagnosis, treatment, and prognostic evaluation of LSCC.