Expression and clinical significance of SALL4 and LGR5 in patients with lung cancer

Abstract

Abstract. Lung cancer is the most frequent cancer worldwide, in terms of incidence and mortality. Due to challenges in the diagnosis of the disease, the 5-year overall survival rate is only ~16%. Previous studies have suggested that malignant transformations originate from adult stem cells, and malignant lesions may therefore express stem-cell-associated markers. The purpose of the present study is to investigate the expression and clinical significance of the stem cell-associated markers Sal-like protein 4 (SALL4) and leucine-rich repeat-containing G-protein coupled receptor 5 (LGR5) in lung cancer, and to provide novel diagnostic markers and targets for the treatment of lung cancer. The expression of the stem cell-associated markers SALL4 and LGR5 was analyzed by immunohistochemistry performed on 135 human lung cancer tissue specimens and 10 non-cancer lung tissue specimens. The clinical significance of the expression of these markers and correlation between their expression and clinical parameters was also assessed. SALL4 expression was highly upregulated in lung cancer tissues, but was not present in non-cancerous lung tissues, and the sensitivity and specificity of SALL4 reached 88% and 100%, respectively. By contrast, LGR5 demonstrated 97% sensitivity, but the specificity was poor. Therefore, SALL4 may be an extremely useful diagnostic marker for lung cancer, but LGR5 is not as useful. IntroductionLung cancer is the most common cancer worldwide, in terms of incidence and mortality, as it comprises 17% of total novel cancer cases and 23% of the total global cancer mortalities (1). In order to improve the survival rate, it is important to diagnose and surgically excise lung cancer at an early stage of disease (2). Therefore, it is necessary to identify biomarkers with the potential to facilitate tumor diagnosis, particularly in the early stages of the disease. The cancer stem cell (CSC) theory proposes that tumors contain a small subpopulation of CSCs, which are responsible for tumor growth, invasion and metastasis (2). CSCs and normal tissue stem cells share important characteristics, including self-renewal, multipotency and unlimited proliferation, and potentially possess overlapping molecular mechanisms (3,4). Currently, a considerable number of stem cell-associated markers have been identified (2,3). Numerous studies have revealed that Sal-like protein 4 (SALL4) and leucine-rich repeat-containing G-protein coupled receptor 5 (LGR5) are also involved in the tumorigenesis, development and metastasis of various tumors (5-7), and these proteins are expected to become potential diagnostic markers and therapeutic targets in cancer.SALL4, a homolog of the Drosophila homeotic gene spalt, is a zinc-finger transcription factor that is required for the proliferation and maintenance of pluripotency through interaction with OCT3/4, sex determining region Y-box 2 and NANOG (8,9). SALL4 is also highly expressed in embryonic stem cells (8)(9)(10)(11)(12). Notably, SALL4 is also overexpressed in various types of human he...

miR-16 targets SALL4 to repress the proliferation and migration of gastric cancer

“…SALL4 is well known to be involved in progression of many human cancers, including colorectal cancer, breast cancer, liver cancer and lung cancer ( 20 , 33 – 35 ), by regulating cell growth, metastasis and invasion. SALL4 expression detected in our experiment was obviously higher in GC consistent with reports that SALL4 was upregulated in GC ( 24 , 36 ).…”

The new advance of SALL4 in cancer: Function, regulation, and implication

“…In esophageal squamous cell carcinoma (ESCC), SALL4 knockdown decreases the expression of the CSC‐related markers such as CD44, CD133, and aldehyde dehydrogenase‐1 (ALDH1) 38 . Finally, SALL4 contributes to the initiation and maintenance of CSCs in leukemia and solid tumors 20,34,39 …”

“…The SALL4 protein is found primarily in the cytoplasm and cell membrane of lung cancer cells. Moreover, SALL4 is overexpressed in 88% of lung cancer tissue samples (119 out of 135 cases), and the sensitivity and specificity of SALL4 expression in lung cancer tissue samples for lung cancer diagnosis are shown to be 88.0% and 100%, respectively 39 . Another study also suggests that SALL4 mRNA expression is present in 80.9% of cancerous tissues (38 of 47) and that the sensitivity and specificity of SALL4 mRNA are 85.1 and 92.9%, respectively, 47 indicating that SALL4 could be used as an important diagnostic marker for lung cancer due to its specific and high expression in cancer cells.…”

SALL4: An Intriguing Therapeutic Target in Cancer Treatment

“…To increase the survival rate of the patients, early diagnosis of the disease and surgically excising it is important. SALL4 aberrant expression is observed in lung cancer patients with poor survival and it is shown to be a good diagnostic marker with 88% sensitivity and 100% specificity in lung cancer patients [ 79 ]. Moreover, Kobayashi et al proposed SALL4 mRNA level as a diagnostic marker for lung cancer with 85.1% sensitivity and 92.9% specificity [ 80 ].…”