A three‐lncRNA signature of pretreatment biopsies predicts pathological response and outcome in esophageal squamous cell carcinoma with neoadjuvant chemoradiotherapy

Abstract

Background Current strategies are insufficient to predict pathologically complete response (pCR) for esophageal squamous cell carcinomas (ESCCs) before treatment. Here, we aim to develop a novel long noncoding RNA (lncRNA) signature for pCR and outcome prediction of ESCCs through a multicenter analysis for a Chinese population. Methods Differentially expressed lncRNAs (DELs) between pCRs and less than pCR (<pCR) in the pretreated cancer biopsies were identified from 28 cases in Guangzhou cohort and verified from 30 cases in Beijing discovery cohort. Then a prediction model was built through Fisher's linear discriminant analysis (FLDA) of 67 cases in Beijing training cohort. Then an internal cohort and an integrated external cohort (Zhengzhou and Anyang cohorts) were used to validate the predictive accuracy. The prognostic value of this signature was also evaluated. Results Twelve DELs were identified from Guangzhou cohort and six lncRNAs were verified. Then, a classifier of three lncRNAs (SCAT1, PRKAG2‐AS1, and FLG‐AS1) was established and achieved a high accuracy with an area under the receiver operating characteristic curve (AUC) of 0.952 in the training cohort, which was well validated in the internal validation cohort and external cohort with the AUCs of 0.856 and 0.817, respectively. Furthermore, the predictive score was identified as the only independent predictor for pCR. Patients with high discriminant score showed a significantly longer overall and relapse‐free survival (P < .05). Conclusions We developed the first and applicable three‐lncRNA signature of pCR and outcome prediction, which is robust and reproducible in multicenter cohorts for ESCCs with nCRT.

Targeting Antisense lncRNA PRKAG2-AS1, as a Therapeutic Target, Suppresses Malignant Behaviors of Hepatocellular Carcinoma Cells

“…Up-regulation of PRKAG2-AS1 was detected in HCC than normal tissue specimens. As previous studies, this lncRNA could be overexpressed in colon adenocarcinoma (13), advanced prostate cancer (14) and esophageal squamous cell carcinoma (15). Our data suggested that PRKAG2-AS1 up-regulation was suggestive of poor OS and DFS.…”

“…Thus, PRKAG2-AS1 could be a promising prognostic factor for HCC. Previously, PRKAG2-AS1 has been identified as a prognostic marker for colon adenocarcinoma (13), advanced prostate cancer ( 14) and esophageal squamous cell carcinoma (15).…”

“…Moreover, its overexpression accelerates tumor malignant growth in HCC. A novel antisense lncRNA PRKAG2-AS1 is overexpressed in colon adenocarcinoma (13), advanced prostate cancer (14) and esophageal squamous cell carcinoma (15). Moreover, its up-regulation could be indicative of unfavorable clinical outcomes of patients.…”

A Novel Immune-Related lncRNA Signature predict the Immune Landscape and Prognosis for Head and Neck Squamous Cell Carcinoma

“…In this study, some of the irlncRNAs in the process of modeling that have been already identi ed play an important role in malignant phenotypes of various cancer types, such as LINC01063 [24,25], HOXC-AS1 [26,27], LINC02454 [28,29] and SCAT1 [30]. Furthermore, previous reports have shown that LINC00460 [31], C5orf66-AS1 [32] and TMPO-AS1 [33] are associated with prognosis and treatment outcomes in HNSCC.…”

Distribution of Peripheral Blood Cells in Esophageal Cancer Patients During Concurrent Chemoradiotherapy Predicts Long-Term Locoregional Progression Hazard After Treatment (GASTO1072)

“…Emerging studies suggest that robust prediction of patient response to CCRT could also be achieved by using a variety of other methodologies, including molecular signature, CT-radiomics, and positron emission tomography. [41][42][43] Combining these markers with PBCS may lead to a greater predictive capability for patient outcomes.…”