The genetic mechanisms underlying the poor prognosis of esophageal squamous cell carcinoma (ESCC) are not well understood. Here, we report somatic mutations found in ESCC from sequencing 10 whole-genome and 57 whole-exome matched tumor-normal sample pairs. Among the identified genes, we characterized mutations in VANGL1 and showed that they accelerated cell growth in vitro. We also found that five other genes, including three coding genes (SHANK2, MYBL2, FADD) and two non-coding genes (miR-4707-5p, PCAT1), were involved in somatic copy-number alterations (SCNAs) or structural variants (SVs). A survival analysis based on the expression profiles of 321 individuals with ESCC indicated that these genes were significantly associated with poorer survival. Subsequently, we performed functional studies, which showed that miR-4707-5p and MYBL2 promoted proliferation and metastasis. Together, our results shed light on somatic mutations and genomic events that contribute to ESCC tumorigenesis and prognosis and might suggest therapeutic targets.

Aberrant expression of receptor interacting protein kinase 4 (RIPK4), a crucial regulatory protein of Wnt/β-catenin signaling, has recently been reported to be involved in several cancers. Here, we report the potential clinical implication and biological functions of RIPK4 in cervical squamous cell carcinoma (CSCC). One hundred and ninety-eight CSCC cases, 109 low-grade squamous intraepithelial lesions (LSILs), 141 high-grade squamous intraepithelial lesions (HSILs) and 63 chronic cervicitis were collected. The expression of RIPK4 was detected by immunohistochemistry (IHC), and its clinical value and oncogenic functions were further assessed. RIPK4 expression increased significantly with disease progression from 3.2% in chronic cervicitis, 19.3% in LSILs and 85.1% in HSILs to 94.4% in CSCCs (P < 0.001). Moreover, RIPK4 may serve as a useful biomarker to distinguish HSIL from chronic cervicitis/LSIL, which are two different clinical types for therapeutic procedures, with a high sensitivity and specificity (85.1% and 86.6%, respectively) and the performance improved when combined with p16INK4a. Further, RIPK4 overexpression was associated with overall (HR = 2.085, P = 0.038) and disease-free survival (HR = 1.742, P = 0.037). Knockdown of RIPK4 reduced cell migration and invasion via inhibition of Vimentin, MMP2 and Fibronectin expression in cervical cancer cells. RIPK4 might act as a potential diagnostic and independent prognostic biomarker for CSCC patients.

BackgroundRecently, studies have shown that plasma D-dimer and serum albumin are prognostic markers for esophageal cancer. The purpose of this study was to evaluate a novel prognostic scoring system—DA score (combination of preoperative plasma D-dimer and serum albumin levels)—and analyze the association between survival of patients with esophageal squamous cell carcinoma (ESCC) and their Glasgow prognostic score.MethodsIn this retrospective study, preoperative biochemical markers and clinicopathologic factors in 260 ESCC patients treated with transthoracic esophagectomy were reviewed. According to receiver operating characteristic analysis, the cutoff values of D-dimer and albumin were defined as 0.5 μg/mL and 43.8 g/L, respectively. Patients with high D-dimer levels (≥0.5 μg/mL) and low albumin levels (<43.8 g/L) were assigned a score of 2, those with only one of the two abnormalities were assigned a score of 1, and those with neither of the two abnormalities were assigned a score of 0.ResultsESCC patients with a DA score of 0, 1, and 2 numbered 55, 116, and 89, respectively. Survival analysis showed that patients with a DA score of 2 had lower overall survival (OS) rates than those with DA scores of 1 and 0 (37.1% vs. 52.6% and 76.4%, P < 0.001); similar findings were observed for disease-free survival (DFS) rates (32.6% vs. 44.8% and 67.3%, P < 0.001). In addition, the predictive value of the DA score was also significant in patients with stages I–IIA and stages IIB–IV ESCC. Multivariate Cox regression analyses indicated that hazard ratios (HRs) for predicting OS of patients with DA scores 1 and 2 were 2.25 (P = 0.010) and 3.14 (P < 0.001), respectively, compared with those with a DA score of 0, and HRs for predicting DFS of patients with DA scores of 1 and 2 were 1.86 (P = 0.023) and 2.68 (P < 0.001), respectively, compared with those with a DA scores of 0.ConclusionsOur study suggests that preoperative DA scores are notably associated with postoperative survival of ESCC patients.