MFAP5 and TNNC1: Potential markers for predicting occult cervical lymphatic metastasis and prognosis in early stage tongue cancer

Abstract

The purpose of this study is to identify candidate genes that could predict prognosis of early-stage tongue squamous cell carcinoma (TSCC) and its occult cervical lymphatic metastasis by large-scale gene expression profiling. Tumor tissue and matched normal mucosa samples were collected from patients with TSCC and analyzed with Affymetrix HTA2.0 high-density oligonucleotide array. Differentially expressed genes in TSCC with cervical lymph node metastasis (CLNM) were further analyzed with Gene Ontology and Kyoto Encyclopedia of Genes and Genomes for their functions and related pathways. A total of 107 differentially expressed genes (p < 0.05) were identified by microarray in TSCC samples with CLNM (n = 6) compared to those without CLNM (n = 6). Genes involved in the cell-matrix adherens junction and migration function including MFAP5, TNNC1, MGP, FBFBP1 and FBXO32 were selected and validated by RT-PCR in TSCC samples (n = 32). Of the five genes, MFAP5 and TNCC1 expressions were further validated by immohistochemistry (n = 61). The significant positive correlation between MFAP5 and TNNC1 expression (p<0.001) was observed. Notably, over-expression of MFAP5 and TNNC1 were correlated with CLNM, metastasis relapse-free survival and overall survival. Our findings indicated that MFAP5 and TNNC1 may be potential markers for predicting occult cervical lymphatic metastasis and prognosis of oral tongue carcinoma.

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“…While changes in gene expression are not always commensurate with alterations in protein expression, cTnC has been observed at the protein level in human lung adenocarcinoma cells (SPCA-1) and human gastric adenocarcinoma cells (BGC 823) [ 24 ]. Changes in TNNC1 expression were also demonstrated in human tongue squamous cell carcinoma (TSCC) tissue with concomitant cervical lymph node metastasis (CLNM) [ 73 ]. Gene microarray analysis and immunohistochemistry results indicated altered TNNC1 expression in early-stage human oral cancer and its association with poor survival [ 73 ].…”

“…Changes in TNNC1 expression were also demonstrated in human tongue squamous cell carcinoma (TSCC) tissue with concomitant cervical lymph node metastasis (CLNM) [ 73 ]. Gene microarray analysis and immunohistochemistry results indicated altered TNNC1 expression in early-stage human oral cancer and its association with poor survival [ 73 ]. Specifically, the results showed a strong association between TNNC1 expression (among others) and CLNM [ 73 ].…”

“…Gene microarray analysis and immunohistochemistry results indicated altered TNNC1 expression in early-stage human oral cancer and its association with poor survival [ 73 ]. Specifically, the results showed a strong association between TNNC1 expression (among others) and CLNM [ 73 ]. It was also noted that TNNC1 might ultimately serve as a future clinical prognostic marker for TSCC and its occult cervical lymphatic metastasis [ 73 ].…”

“…Specifically, the results showed a strong association between TNNC1 expression (among others) and CLNM [ 73 ]. It was also noted that TNNC1 might ultimately serve as a future clinical prognostic marker for TSCC and its occult cervical lymphatic metastasis [ 73 ].…”

“…Fast skeletal TnI ( TNNI2 ) inhibits (T-bar) endothelial cell proliferation and angiogenesis [ 27 , 84 – 86 ]. Overexpression of TNNC1 and TNNI1 promotes (arrow bar) solid tumor growth and metastasis [ 23 , 72 , 73 ].…”