Deregulation of L1 retrotransposon-encoded protein expression in oral cancer recurrence

Background: Oral squamous cell carcinoma (OSCC) often shows recurrence after surgery. To date, there is no significant study on OSCC that predicts recurrence after surgical removal of the cancer. Long INterpersed Element 1 (LINE-1 or L1) retrotransposons show very high activity in many cancers, suggesting a potential role in cancer onset and progression. We wished to assess the value of LINE-1 retrotransposon-encoded proteins (L1ORF1p and L1ORF2p) as biomarkers of OSCC recurrence along with eight other established cancer biomarkers (p53, PCNA, CD105, ki67, MMP9, EGFR, PDL1, and CD44). Results: We collected 114 post-operative oral cancer patient samples, mostly from tobacco-addicted patients, and analysed the expression of both L1ORF1p and L1ORF2p and eight established cancer biomarkers (p53, PCNA, CD105, ki67, MMP9, EGFR, PDL1, and CD44) by immunohistochemistry. We found 97% of samples (110 out of 114) showed significant expression of both the L1-encoded proteins. Among those 114 samples, 35 samples belonged to the recurrent group and showed strong association with L1ORF1p and L1ORF2p expression when compared with the non-recurrent group. Expression analysis of eight established cancer biomarkers (p53, PCNA, CD105, ki67, MMP9, EGFR, PDL1, and CD44) by immunohistochemistry showed L1 proteins, along with CD105 and EGFR, can form a predictive panel for OSCC recurrence. Conclusions: The study revealed that the combined expression analysis of the four bio-markers (L1ORF1p, L1ORF2p, CD105 and EGFR) can distinguish recurrent from the non-recurrent OSCC samples. The findings have significant clinical relevance and applications in predicting oral cancer recurrence.