A novel non-invasive mRNA-lncRNA biomarker panel for accurate prediction of cervical squamous cell carcinoma and adenocarcinoma

Squamous cell carcinoma (SCC) and adenocarcinoma (ADC) represent predominant histological subtypes of cervical cancer. To improve screening efficacy, we leveraged RNA sequencing data from 4 cervical SCC samples, 4 cervical ADC samples, and 8 normal cervix samples and conducted a comprehensive mRNA and long noncoding RNA (lncRNA) profiling analysis followed with a multi-phase study comprising 556 samples. Validating the RNA sequencing data in a clinical sample set comprising 45 normal cervix tissues, 45 SCC tissues, and 45 ADC tissues, we identified 9 mRNAs (SMC1B, OTX1, GRP, CELSR3, HOXC6, ITGB6, WDR62, SEPT3, and KLHL34) and 4 lncRNAs (FEZF1-AS1, LINC01305, LINC00857, and LINC00673) differentially expressed in both SCC and ADC samples. Utilizing quantitative reverse transcription polymerase chain reaction analysis and receiver operating characteristic (ROC) curve analysis in a training set (45 normal, 126 SCC, and 82 ADC tissues), we refined a novel mRNA-lncRNA-based panel (SMC1B/CELSR3/FEZF1-AS1/LINC01305). Employing logistic regression model and ROC analysis, this panel exhibited significant distinctions and promising area under the curve (AUC) values in both SCC (AUC=0.9520, p<0.0001) and ADC (AUC=0.9748, p<0.0001) tissues. Subsequent validation in an independent set (11 normal, 32 SCC, and 20 ADC tissues) demonstrated its diagnostic accuracy in both SCC (AUC=0.9659, p<0.0001) and ADC (AUC=0.9636, p<0.0001) patients. Notably, this tissue-based biomarker panel robustly discriminated precancerous lesion and cervical cancer patients from non-disease controls in a blood-based validation set (30 normal, 25 HSIL and 50 cervical cancer) with an AUC value of 0.9320. This study presents a non-invasive, efficient diagnostic panel for cervical cancer screening.