Aberrations in SMAD family of genes among HNSCC patients

Abstract

Head and neck cancer is a debilitating disease with several etiological factors. One of the main etiologies to be noticed is the alteration, which is either caused by genetic or environmental factors. Therefore, it is of interest to assess the effect of genetic alterations, especially the non-synonymous mutations of the SMAD gene family and its possible association with HNSCC. Data shows a significant novel mutation in the SMAD gene family in association with head and neck squamous cell carcinoma (HNSCC), which would aid in better diagnosis and treatment planning for cancer.

Keywords: Cancer; SMAD gene; genetic alteration; head & neck; mutation; pathogenicity.

Figure 1

The oncoprint data depicting different types of genetic alteration in the SMAD family of genes. The SMAD4 was found to have the highest alteration level of all genes examined (7%). SMAD2 and SMAD7 genes were found to have numerous sites of amplification.

Figure 2

Box-Whisker plot representing the differential gene expression pattern of the SMAD4 gene across different tumor grades. The X-axis represents the different grades of HNSCC example samples from the TCGA data set and the Y axis denotes the transcripts per million values. A significant difference in the gene expression profile was observed between normal vs grade 1 (p = 1.49 x 10-4 ), normal vs grade 3 (p = 9.5 x 10-12), normal vs grade 4 (1.11 x 10-6), grade 1 vs grade 2 (p = 2.166 x 10-4 ), grade 1 vs grade 3 (p = 2.90 x 10-7), grade 1 vs grade 4 (p = 4.39 x 10-8), grade 2 vs grade 3 (p = 7.44 x 10-3), grade 2 vs grade 4 (p = 5.77 x 10-4) and grade 3 vs grade 4 (p = 1.98 x 10-2). A p-value of less than 0.05 is considered to be significant.

Figure 3

Kalplan-Meier plot showing the association of altered SMAD expression with HNSCC patients' survival. The X-axis represents time in days and Y-axis represents survival probability in HNSCC patients. The red line corresponds to high-level expression and the blue line corresponds to low/ medium level expression of SMAD (0.12). A p-value of more than 0.05 is not considered to be significant.