Background: The aim of the present study was to identify the potential long non-coding (lnc.)-RNA and its associated molecular mechanisms involved in the regulation of the radiosensitivity of esophageal squamous cell cancer (ESCC) in order to assess whether it could be a biomarker for the prediction of the response to radiotherapy and prognosis in patients with ESCC. Methods: Microarrays and bioinformatics analysis were utilized to screen the potential lncRNAs associated with radiosensitivity in radiosensitive (n = 3) and radioresistant (n = 3) ESCC tumor tissues. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was performed in 35 ESCC tumor tissues (20 radiosensitive and 15 radioresistant tissues, respectively) to validate the lncRNA that contributed the most to the radiosensitivity of ESCC (named the candidate lncRNA). MTT, flow cytometry, and western blot assays were conducted to assess the effect of the candidate lncRNA on radiosensitivity in vitro in ECA109/ECA109R ESCC cells. A mouse xenograft model was established to confirm the function of the candidate lncRNA in the radiosensitivity of ESCC in vivo. The putative downstream target genes regulated by the candidate lncRNA were predicted using Starbase 2.0 software and the TargetScan database. The interactions between the candidate lncRNA and the putative downstream target genes were examined by Luciferase reporter assay, and were confirmed by PCR. Results: A total of 113 aberrantly expressed lncRNAs were identified by microarray analysis, of which family with sequence similarity 201-member A (FAM201A) was identified as the lncRNA that contributed the most to the radiosensitivity of ESCC. FAM201A was upregulated in radioresistant ESCC tumor tissues and had a poorer short-term response to radiotherapy resulting in inferior overall survival. FAM201A knockdown enhanced the radiosensitivity of ECA109/ECA109R cells by upregulating ataxia telangiectasia mutated (ATM) and mammalian target of rapamycin (mTOR) expression via the negative regulation of miR-101 expression. The mouse xenograft model demonstrated that FAM201A knockdown improved the radiosensitivity of ESCC. Conclusion: The lncRNA FAM201A, which mediated the radiosensitivity of ESCC by regulating ATM and mTOR expression via miR-101 in the present study, may be a potential biomarker for predicting radiosensitivity and patient prognosis, and may be a therapeutic target for enhancing cancer radiosensitivity in ESCC.

Accumulating evidence indicates that inflammation and nutrition status are associated with clinical outcomes in patients with various malignancies. This study aimed to evaluate the prognostic significance of the pretreatment platelet to albumin ratio (PAR) in esophageal squamous cell carcinoma (ESCC) patients undergoing definitive radiotherapy. A total of 470 patients who underwent definitive radiotherapy with or without chemotherapy were enrolled. The optimal cut-off values of PAR and other indicators were determined by the X-tile. The Kaplan–Meier method, multivariate analyses Cox regression were conducted to identify the association between those indicators and the survival outcomes. The median follow-up time was 23.5 months. The optimal cut-off value of PAR was 5.7 × 10⁹ and patients were stratified as the low PAR group and the high PAR group. In the univariate analysis, a low overall survival rate was significantly associated with T stage (P = 0.005), TNM stage (P < 0.001), Adjuvant chemotherapy (P = 0.007), neutrophil to lymphocyte ratio (NLR) (P = 0.006), platelet to lymphocyte ratio (P < 0.001), systemic immune-inflammation index (P < 0.001), prognostic nutritional index (P < 0.001) and platelet to albumin ratio (PAR) (P < 0.001). Patients with high PAR were associated with poorer OS and PFS than patients with low PAR. On multivariate analysis, TNM stage (P = 0.001), adjuvant chemotherapy (P < 0.001), and PAR (P = 0.033) were independent prognostic factors in ESCC treated with definitive radiotherapy. PAR is a novel, convenient, and inexpensive prognostic indicator for patients with ESCC undergoing definitive radiotherapy. Future validation from prospective larger-scale studies is warranted.

FAM72A-D promote the self-renewal of neural progenitor cells. There is accumulating evidence that FAM72 promotes tumorigenicity. However, its effects in lung adenocarcinoma (LUAD) have not been determined. Thus, we evaluated the prognostic value of FAM72A-D in LUAD using bioinformatics approaches. In particular, we evaluated the relationship between FAM72 and LUAD using a wide range of databases and analysis tools, including TCGA, GEO, GEPIA, Metascape, cBioPortal, and MethSurv. Compared with its expression in normal lung tissues, FAM72 expression was significantly increased in LUAD tissues. A univariate Cox analysis showed that high FAM72 expression levels were correlated with a poor OS in LUAD. Additionally, FAM72 expression was independently associated with OS through a multivariate Cox analysis. GO and GSEA revealed enrichment in mitotic nuclear division and cell cycle. Moreover, high FAM72 expression was associated with poor survival. An analysis of immune infiltration showed that FAM72 is correlated with immune cell infiltration. Finally, we found that the methylation level was associated with prognosis in patients with LUAD. In summary, these results indicate that FAM72 is a potential molecular marker for poor prognosis in LUAD and provide additional insight for the development of therapies and prognostic markers.

The aim of this study was to assess the prognostic significance of preoperative systemic inflammation score (SIS) on patients with esophageal squamous cell carcinoma (ESCC). A total of 357 ESCC patients who accepted radical esophagectomy between January 2008 and December 2009 at our institution were recruited in the analysis. The cut-off finder application was used to calculate the optimal cutoff values. The Chi-squared test or Fisher’s exact test were used to analyze categorical variables. Overall survival (OS) was calculated using the Kaplan-Meier method and the log-rank test. Multivariate analysis was calculated using Cox regression analysis model. A model combining SIS was created and its performance was evaluated using the Akaike information criterion (AIC) and concordance index (C-index). The median follow-up time was 58 months (range, 1–84 months). The 5-year OS rate was 50% (95% CI, 49.94–50.06%). The optimal cut-off values for preoperative neutrophil to lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio (LMR) and serum albumin (Alb) were 2.27, 3.79 and 36.55, respectively. Univariate analyses revealed that gender (P = 0.047), T stage (P < 0.001), N stage (P < 0.001), vascular invasion (P < 0.001), tumor location (P = 0.018), tumor length(P < 0.001), NLR (P = 0.006), LMR (P = 0.007), serum Alb (P = 0.001), and SIS (P < 0.001) were significantly associated with OS. Independent prognostic factors for OS were T stage, N stage, tumor location, tumor length, and SIS. However, NLR was not an independent prognostic factor in multivariate analysis. The model combining SIS had smaller AIC and higher C-index compared to the model without SIS, which suggesting that the adding the SIS to the multivariate model increasing the predictive accuracy of the OS in the ESCC patients treated with radical esophagectomy and 3-field lymphadenectomy (3-FL). SIS may treat as a novel prognostic factor than NLR for ESCC patients who underwent radical esophagectomy and 3-FL. However, Larger-scale studies are needed to validate these findings.

GREB1L is a protein-coding gene that is an important paralog of GREB1. However, its effects in lung adenocarcinoma (LUAD) have not been determined. Thus, we evaluated the prognostic value of GREB1L in LUAD using bioinformatics approaches. In particular, we evaluated the relationship between GREB1L and LUAD using a wide range of databases and analysis tools, including TCGA, GEO, HPA, TIMER, cBioPortal, and MethSurv. Compared with its expression in normal lung tissues, GREB1L expression was significantly increased in LUAD tissues. A univariate Cox analysis showed that high GREB1L expression levels were correlated with a poor OS in LUAD. Additionally, GREB1L expression was independently associated with OS through a multivariate Cox analysis. GSEA analysis revealed enrichment in cell cycle, immune regulation, and methylation. Moreover, high GREB1L expression was associated with poor survival. We also found that the methylation and genetic alteration level was associated with prognosis in patients with LUAD. Finally, an analysis of immune infiltration showed that GREB1L is correlated with immune cell infiltration, PD-1, and PD-L1. In summary, these results indicate that GREB1L is a potential molecular marker for poor prognosis in LUAD and provide additional insight for the development of therapies and prognostic markers.

The prognostic nutritional index (PNI) has been found to have prognostic value in several cancers, and we aimed to determine its predictive value for the long-term prognosis of cervical esophageal squamous cell carcinoma (CESCC) patients treated with chemoradiotherapy (CRT). The data for 106 CESCC patients who received radiotherapy with or without chemotherapy at the Cancer Hospital of Fujian Medical University from June 1, 2000 to December 31, 2015 were retrospectively analyzed. According to serum measurements taken before therapy, the PNI was calculated as albumin (g/L) + 5 × total lymphocyte count. The association between PNI and overall survival (OS) was determined by the Kaplan-Meier method and Cox proportional regression model analysis. The median follow-up time was 19 months. The optimal cutoff value for PNI was calculated to be 48.15, and patients were divided into a low PNI group (<48.15) and high PNI group (≥48.15). Univariate analysis showed that a low survival rate was significantly associated with male gender (P=0.004), tumor length ≥5.0 cm (P=0.043), radiotherapy technique (P=0.016), synchronous chemotherapy (P=0.012), lymphocyte-monocyte ratio (LMR) (P=0.007), neutrophil-lymphocyte ratio (NLR) (P=0.007), lung cancer inflammation index (ALI) (P=0.008), cervical esophageal carcinoma inflammation index (CEI) (P=0.043), and PNI (P<0.001). The OS was higher in the high PNI group than in the low PNI group. On multivariate analysis, gender (P=0.004), radiotherapy technique (P=0.029), and PNI (P=0.007) were independent prognostic factors in CESCC treated with CRT. The PNI value is a simple, reliable, and reproducible indicator for improving the accuracy of patient prognosis. And larger-scale studies are warranted to validate these findings.