Correlation between loss of Smad4 and clinical parameters of non-small cell lung cancer: an observational cohort study

Abstract

Background SMAD4 has been found to be inactivated to varying degrees in many types of cancer; the purpose of this study was to investigate the correlation between SMAD4 expression in non-small cell lung cancer (NSCLC) and clinical pathological parameters. Methods The serum concentration of SMAD4 was measured by enzyme-linked immunosorbent assay and its histological expression was quantified by immunohistochemistry. Results The serum concentration of Smad4 in patients with NSCLC was lower than that in benign lung disease patients and healthy individuals (P < 0.001) and its concentration was related to the histological classification, pathological differentiation, lymphatic metastasis and clinical stage of NSCLC. The sensitivity and specificity of serum Smad4 were 91.56% and 61.56% for screening NSCLC from healthy individuals and 84.55% and 60.36% for screening NSCLC from patients with benign lung disease. Logistic regression analysis showed that the degree of cell differentiation (P < 0.001), lymph node metastasis (P < 0.001) and clinical stage of NSCLC (P = 0.007) affected the expression of Smad4, and had a strong correlation with the expression of Smad4. The expression of Smad4 in NSCLC tissues was lower than that in normal lung tissues (P = 0.009) and its expression was related to the degree of tissue differentiation, lymph node metastasis and clinical stage (P < 0.05). Conclusions The downregulation or deletion of Smad4 is related to the malignant biological behavior of NSCLC and serum Smad4 could be considered as a potential molecular indicator for diagnosis and evaluation of NSCLC.

Single Circulating-Tumor-Cell-Targeted Sequencing to Identify Somatic Variants in Liquid Biopsies in Non-Small-Cell Lung Cancer Patients

“…The findings of that study indicated that variants of the SMAD4 gene play an important role for NSCLC metastasis as they were observed in advanced stage IV patients only. SMAD4 serum concentration also correlated with a malignant NSCLC phenotype that was associated with metastasis and clinical progression [39]. In addition, SMAD4 and its transcription factor play a regulatory function for many target genes, also increasing the risk of cell tumorigenesis in lung cancer [40].…”

Clinicopathological and prognostic significance of SMAD4 in non-small cell lung cancer: A meta-analysis and database validation

“…Finally, 8 studies involving 1461 NSCLC patients were included. [10][11][12][14][15][16][17][18] The 8 studies were published from 2011 to 2021 and were all retrospective studies, and the sample sizes of the included studies were between 28 and 963. The information of the 8 included studies is listed in Table 1.…”

“…Many recent studies have detected a relationship between SMAD4 expression and the clinicopathological parameters of NSCLC. Guo et al [10] investigated the correlation between SMAD4 expression in NSCLC tissues and clinicopathological significance and found that SMAD4 levels were lower in NSCLC tissues, and the low expression of SMAD4 was related to tumor differentiation, lymph node metastasis and the TNM stage of NSCLC patients. However, the relationship between SMAD4 expression and the clinicopathologic parameters of NSCLC patients is still controversial.…”

“…Guo et al found that SMAD4 had a strong correlation with the differentiation and lymph node metastasis of NSCLC patients. [10] However, Xie et al [11] found that SMAD4 expression was not related to the differentiation and lymph node metastasis of NSCLC patients. In addition, inconsistent results concerning the prognostic value of Smad4 in NSCLC were also found in different articles.…”

SMAD4 Expression in Monocytes as a Potential Biomarker for Atherosclerosis Risk in Patients with Obstructive Sleep Apnea

“…Since the Smad family has been typically defined as comprising intracellular signal transductor proteins, a major concern of this study was to elucidate the origin of plasmatic sSMAD4. Interestingly, previous studies reported elevated levels of Smad proteins in the serum of patients with major diseases of pleiotropic origin such as non-small cell lung cancer or coronary artery disease [54,55]. However, none of these studies assessed the source of these Smad soluble forms, nor explored mechanisms underlying Smad delivery to the extracellular space.…”