Significance of Heterogeneous Nuclear Ribonucleoprotein B1 as a New Early Detection Marker for Oral Squamous Cell Carcinoma

Abstract

The development of an early tumor detection marker for oral cancer is an obvious need due to the high recurrence rate and poor survival rate. Based on our previous report that overexpression of heterogeneous nuclear ribonucleoprotein (hnRNP) B1 protein was found in 100% of squamous cell carcinomas of human lung, we applied the same immunohistochemical method, using anti-hnRNP B1 antibody, to human oral squamous cell carcinoma (OSCC). Seven human tissue sections of OSCC showed strong staining with anti-hnRNP B1 antibody, and hnRNP B1 protein of 37 kDa was identified in protein fractions isolated from six of the cancerous tissue sections, while it was not found in adjacent noncancerous tissue. Moreover, three non-homogeneous (nodular) leukoplakia sections showed significant anti-hnRNP B1 staining. The results suggest that this antibody detects precancerous lesions as well as advanced lesions (stages I to IV) of OSCC. We also present positive results of cytodiagnosis for two smear specimens. All of the above results indicate that hnRNP B1 is a new and useful marker for early detection of OSCC. Key words: Oral precancerous lesion -Oral leukoplakia -Cytodiagnosis -Biomarker -ChemopreventionRecently we reported that overexpression of heterogeneous nuclear ribonucleoprotein (hnRNP) B1 of 37 kDaand not hnRNP A2, as had previously been believed-is a good biomarker for the detection of human lung cancer. 1) hnRNP B1 is identical to hnRNP A2 with the addition of 12 amino acids at the N-terminus, a difference probably deriving from alternative splicing.2) hnRNP A2/B1 protein is a major component of the hnRNP core complex in mammalian cell nuclei, and is involved in RNA splicing in nuclei, as well as in mRNA transport from nucleus to cytoplasm.3) In a study on the expression of hnRNP B1 in both human lung cancer cell lines and human lung cancer tissue, we found that cancer cells showed significant positive staining of hnRNP B1 with anti-hnRNP B1 antibody, and that squamous cell carcinomas showed 100% positive staining.1) These results encouraged us to see whether molecular diagnosis of human lung cancer with antihnRNP B1 could be extended to human oral squamous cell carcinoma (OSCC).Success in early detection of oral cancer is of great value, since human oral cancer has a high recurrence rate and is associated with cosmetic disruption in the advanced stage. Although various tumor markers, such as carcinoembryonic antigen (CEA), 4) squamous cell carcinoma-antigen (SCC), 5) glutathione S-transferase-π (GST-π), 6, 7) and cytokeratins, 8,9) are currently being used as diagnostic aids for OSCC, all these markers have proved to be insufficiently sensitive and reliable for the early detection of OSCC and prediction of its recurrence. Thus, the establishment of a new tumor marker with increased specificity and sensitivity for early lesion of OSCC is a high priority.We first found that anti-hnRNP B1 antibody stained cancer cells of seven human tissue sections of OSCC. Next, by western blotting we detected a protein band (37 kDa) of h...

HnRNP E2 is downregulated in human oral cancer cells and the overexpression of hnRNP E2 induces apoptosis

“…Enhanced expression of hnRNPB1 is also observed in cancerous regions of tissue specimens from oesophageal SCC compared to noncancerous region [19]. HnRNPH and hnRNPB1 were upregulated in human oral cancer [20,21]. A recent report recognizes hnRNPG to be a tumor suppressor against human oral SCC [22].…”

Altered patterns of expression of members of the heterogeneous nuclear ribonucleoprotein (hnRNP) family in lung cancer

“…In both cases, hnRNP A2/B1 has been proposed as a marker for early stages of cancer development [23,24]. hnRNP B1 is also detected in precancerous lesions as well as advanced lesions of human oral squamous cell carcinoma, indicating that hnRNP B1 may be a useful marker for early detection [50]. Surprisingly, a reduction in cytoplasmic staining for hnRNP A2/ B1 was observed in thyroid carcinomas when compared with hyperplastic and adenomatous lesions [51].…”

Detection of plasma hnRNP B1 mRNA, a new cancer biomarker, in lung cancer patients by quantitative real-time polymerase chain reaction

“…We subsequently identified hnRNP B1, a splicing variant of hnRNP A2, and found that it was overexpressed in nuclei of human lung cancer cells from the early stage to the advanced [8][9][10]. Moreover, hnRNP B1 was overexpressed in squamous cell carcinoma in various organs, such as oral cavity and esophagus, in addition to lung [11,12].…”