Abstract
Objective To develop and validate a novel RNA-seq-based nomogram for preoperative prediction of lymph node metastasis (LNM) for patients with oral squamous cell carcinoma (OSCC). Methods RNA-seq data for 276 OSCC patients (including 157 samples with LNM and 119 without LNM) were downloaded from TCGA database. Differential expression analysis was performed between LNM and non-LNM of OSCC. These samples were divided into a training set and a test set by a ratio of 9 : 1 while the relative proportion of the non-LNM and LNM groups was kept balanced within each dataset. Based on clinical features and seven candidate RNAs, we established a prediction model of LNM for OSCC using logistic regression analysis. Tenfold crossvalidation was utilized to examine the accuracy of the nomogram. Decision curve analysis was performed to evaluate the clinical utility of the nomogram. Results A total of 139 differentially expressed RNAs were identified between LNM and non-LNM of OSCC. Seven candidate RNAs were screened based on FPKM values, including NEURL1, AL162581.1 (miscRNA), AP002336.2 (lncRNA), CCBE1, CORO6, RDH12, and AC129492.6 (pseudogene). Logistic regression analysis revealed that the clinical N stage (p < 0.001) was an important factor to predict LNM. Moreover, three RNAs including RDH12 (p value < 0.05), CCBE1 (p value < 0.01), and AL162581.1 (p value < 0.05) could be predictive biomarkers for LNM in OSCC patients. The average accuracy rate of the model was 0.7661, indicating a good performance of the model. Conclusion Our findings constructed an RNA-seq-based nomogram combined with clinicopathology, which could potentially provide clinicians with a useful tool for preoperative prediction of LNM and be tailored for individualized therapy in patients with OSCC.
Highlights
Oral squamous cell carcinoma (OSCC) accounts for 95% of all oral malignancies, and its five-year survival rate is up to 50%-60% [1]
Our study developed a model for the preoperative prediction of lymph node metastasis (LNM)
157 (56.88%) patients had LNM. 265 patients possessed complete clinical N status; among them, 44 had no lymph node metastasis in clinical examination but metastasis occurred in the pathological diagnosis. 22 patients’ clinical examination indicated lymph node metastasis, but pathological examination results showed no lymph node metastasis
Summary
Oral squamous cell carcinoma (OSCC) accounts for 95% of all oral malignancies, and its five-year survival rate is up to 50%-60% [1]. Lymph node metastasis (LNM) is considered to be an independent prognostic factor of OSCC, which is associated with tumor recurrence and prognosis [2,3,4]. 25-40% of OSCC patients with LNM at diagnosis will survive 5 years, compared to approximately 90% of those without LNM (non-LNM) [5]. There is still no widely accepted method for noninvasive detection for preoperative prediction of LNM in OSCC currently. For OSCC patients with clinically negative neck (cN0), whether to perform cervical lymph node dissection remains a hot topic. Using current methods to predict LNM, approximately 70% of patients with cN0 OSCC who undergo elective neck dissection (END) are found to be pathologically node negative [6]. It is imminent to best select patients with LNM who will benefit from END and to decrease the cost and morbidity of neck dissection in those without LNM [7]
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