Immunohistochemical Expression of Five Protein Combinations Revealed as Prognostic Markers in Asian Oral Cancer

Oral squamous cell carcinoma (OSCC) has a high mortality rate (similar to 50%), and the 5-year overall survival rate is not optimal. Cyto- and histopathological examination of cancer tissues is the main strategy for diagnosis and treatment. In the present study, we aimed to uncover immunohistochemical (IHC) markers for prognosis in Asian OSCC. From the collected 742 synthetic lethal gene pairs (of various cancer types), we first filtered genes relevant to OSCC, performed 29 IHC stains at different cellular portions and combined these IHC stains into 398 distinct pairs. Next, we identified novel IHC prognostic markers in OSCC among Taiwanese population, from the single and paired IHC staining by univariate Cox regression analysis. Increased nuclear expression of RB1 [RB1(N)up arrow], CDH3(C)up arrow-STK17A(N)up arrow and FLNA(C)up arrow-KRAS(C)up arrow were associated with survival, but not independent of tumor stage, where C and N denote cytoplasm and nucleus, respectively. Furthermore, multivariate Cox regression analyses revealed that CSNK1E(C)down arrow-SHC1(N)down arrow (P = 5.9 x 10(-5); recommended for clinical use), BRCA1(N)down arrow-SHC1(N)down arrow (P = 0.030), CSNK1E(C)down arrow-RB1(N)up arrow (P = 0.045), [CSNK1E(C)-SHC1(N), FLNA(C)-KRAS(C)] (P = 0.000, rounded to three decimal places) and [BRCA1(N)-SHC1(N), FLNA(C)-KRAS(C)] (P = 0.020) were significant factors of poor prognosis, independent of lymph node metastasis, stage and alcohol consumption. An external dataset from The Cancer Genome Atlas HNSCC cohort confirmed that CDH3 up arrow-STK17A up arrow was a significant predictor of poor survival. Our approach identified prognostic markers with components involved in different pathways and revealed IHC marker pairs while neither single IHC was a marker, thus it improved the current state-of-the-art for identification of IHC markers.

Automated summary

This study identified novel immunohistochemical (IHC) prognostic markers for Asian oral squamous cell carcinoma (OSCC). Through multivariate analysis, significant IHC marker pairs were identified, improving the current state-of-the-art for identification of IHC markers.