Guohua Ren

Recent studies have demonstrated that deregulated microRNA (miRNA/miR) expression has a profound impact on biological and pathological processes; abnormal miR-1469 expression was detected in several human malignancies. In the present study, the clinicopathological and prognostic significance of miR-1469 was assessed in 129 patients with esophageal squamous cell cancer (ESCC) who successfully underwent esophagectomy and esophagogastrostomy. Low miR-1469 expression was identified to be significantly associated with tumor invasion depth (P=0.026), lymph node metastasis status (P<0.001) and pathological tumor stage (P<0.001). Survival analysis demonstrated that patients with low miR-1469 expression had significantly poorer disease-free survival (DFS) (18.2 vs. 43.2%; P=0.004) and overall survival (29.1 vs. 47.3%; P=0.029) 5 years following surgery compared with patients with high miR-1469 expression. Univariate survival analysis demonstrated that low miR-1469 expression significantly predicted unfavorable 5-year DFS among patients with N1-3 disease (7.1 vs. 31.8%; P=0.043). The results from the present study indicate that miR-1469 expression could be used in the clinic to predict ESCC progression and prognosis. This will aid in the identification of high-risk patients with ESCC that require more aggressive therapeutic interventions.

Background: Limited data are available on applying circulating tumor DNA (ctDNA) in metastatic triple-negative breast cancer (mTNBC) patients. Here, we investigated the value of ctDNA for predicting the prognosis and monitoring the treatment response in mTNBC patients. Methods: We prospectively enrolled 70 Chinese patients with mTNBC who had progressed after ≤2 lines of chemotherapy and collected blood samples to extract ctDNA for 457-gene targeted panel sequencing. Results: Patients with ctDNA+, defined by 12 prognosis-relevant mutated genes, had a shorter progression-free survival (PFS) than ctDNA− patients (5.16 months vs . 9.05 months, p=0.001), and ctDNA+ was independently associated with a shorter PFS (HR, 95% CI: 2.67, 1.2–5.96; p=0.016) by multivariable analyses. Patients with a higher mutant-allele tumor heterogeneity (MATH) score (≥6.316) or a higher ctDNA fraction (ctDNA%≥0.05) had a significantly shorter PFS than patients with a lower MATH score (5.67 months vs .11.27 months, p=0.007) and patients with a lower ctDNA% (5.45 months vs . 12.17 months, p&lt;0.001), respectively. Positive correlations with treatment response were observed for MATH score ( R =0.24, p=0.014) and ctDNA% ( R =0.3, p=0.002), but not the CEA, CA125, or CA153. Moreover, patients who remained ctDNA+ during dynamic monitoring tended to have a shorter PFS than those who did not (3.90 months vs . 6.10 months, p=0.135). Conclusions: ctDNA profiling provides insight into the mutational landscape of mTNBC and may reliably predict the prognosis and treatment response of mTNBC patients. Funding: This work was supported by the National Natural Science Foundation of China (Grant No. 81902713), Natural Science Foundation of Shandong Province (Grant No. ZR2019LZL018), Breast Disease Research Fund of Shandong Provincial Medical Association (Grant No. YXH2020ZX066), the Start-up Fund of Shandong Cancer Hospital (Grant No. 2020-PYB10), Beijing Science and Technology Innovation Fund (Grant No. KC2021-ZZ-0010-1).