Molecular characteristics and multivariate survival analysis of 43 patients with locally advanced or metastatic esophageal squamous cell carcinoma.

Background: Esophageal cancer (EC) is an aggressive malignant tumor with poor prognosis and high incidence. It is the sixth leading cause of cancer-related death in the world, and the 5-year overall survival (OS) rate is only 12-20%. The rapid development of next-generation sequencing (NGS) has provided powerful help for the treatment and management of EC patients. Methods: Tumor tissue and blood samples of 43 Chinese patients with nonsurgical esophageal squamous cell carcinoma (ESCC) were sequenced using a 425 gene-panel. Genomic profiling was explored and and the Cox proportional hazards model was used to analyze the correlations between gene or signaling pathway alterations and prognosis. Results: In this study, the most common mutated genes were TP53 (90.5%), CCND1 (45.2%), FGF19 (38.1%), NOTCH1 (26.2%), PI3KCA (21.4%) and CDKN2A (19%). Among these mutations, PI3KCA and NOTCH1 showed mutual exclusion to some extent. In the univariate model, mutations in NOTCH1, CBLB and TSC2 genes and tumor mutation burden (TMB) ≥7 were independent biomarkers of OS. NOTCH1 (P=0.007, HR =2.87), CBLB (P=0.011, HR =4.68) and TSC2 (P=0.024, HR =3.7) were significantly associated with poorer OS, and patients with TMB ≥7 had longer OS (P=0.151, HR =0.31). In addition, patients who carried alteration in NOTCH signaling pathway had reduced OS (P=0.014, HR =2.54). Conclusions: NOTCH1, CBLB and TSC2 alterations were found to be potential indicators of poor prognosis in patients with ESCC. TMB was also positively correlated with the OS of ESCC patients, providing valuable insights for their treatment strategies.

Identification of cervical squamous cell carcinoma feature genes and construction of a prognostic model based on immune-related features.

As heterogeneity of cervical squamous cell carcinoma (CSCC), prognosis assessment for CSCC patients remain challenging. To develop novel prognostic strategies for CSCC patients, associated biomarkers are urgently needed. This study aimed to cluster CSCC samples from a molecular perspective. CSCC expression data sets were obtained from The Cancer Genome Atlas and based on the accessed expression profile, a co-expression network was constructed with weighted gene co-expression network analysis to form different gene modules. Tumor microenvironment was evaluated using ESTIMATE algorithm, observing that the brown module was highly associated with tumor immunity. CSCC samples were clustered into three subtypes by consensus clustering based on gene expression profiles in the module. Gene set variation analysis showed differences in immune-related pathways among the three subtypes. CIBERSORT and single-sample gene set enrichment analysis analyses showed the difference in immune cell infiltration among subtype groups. Also, Human leukocyte antigen protein expression varied considerably among subtypes. Subsequently, univariate, Lasso and multivariate Cox regression analyses were performed on the genes in the brown module and an 8-gene prognostic model was constructed. Kaplan-Meier analysis illuminated that the low-risk group manifested a favorable prognosis, and receiver operating characteristic curve showed that the model has good predictive performance. qRT-PCR was used to examine the expression status of the prognosis-associated genes. In conclusion, this study identified three types of CSCC from a molecular perspective and established an effective prognostic model for CSCC, which will provide guidance for clinical subtype identification of CSCC and treatment of patients.

The Effects of Transcutaneous Acupoint Electrical Stimulation on Cancer-related Fatigue and Negative Emotions in Cancer Patients: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Transcutaneous electrical acupoint stimulation (TEAS) is a noninvasive and therapeutic technique that stimulated the acupoint by delivering electricity. Whether TEAS could relieve cancer-related fatigue (CRF), anxiety, and depression and improve the quality of life in cancer patients remains controversial. Thus, we conducted a thorough literature search of electronic Chinese and English databases for randomized controlled trials (RCTs) reporting the effect of CRF, anxiety, depression, and quality of life in cancer patients from inception to July 1st, 2021. The Cochrane Collaboration Risk of Bias criteria were used to assess the risk of bias for each included RCT. Continuous variables were analyzed using standardized mean difference (SMD) and 95% confidence interval (CI). A fixed-effects model was used for the meta-analysis of all outcomes. A total of nine RCTs with 924 cancer patients were included in this analysis, including 460 patients in the interventional group and 464 patients in the control group. We found that TEAS could significantly reduce CRF, depression, and anxiety (SWD = -0.83, 95% CI: -0.99 to -0.66, P < 0.05) and improve the quality of life (SWD = -1.37, 95% CI: -2.34 to -0.40, P < 0.05). The funnel plot analysis revealed no significant publication bias. We conclude that TEAS is beneficial for reducing CRF, depression, and anxiety and improving the quality of life of cancer patients, but additional high-quality evidence in the future is entailed to support this.

Grainyhead-Like Genes Family May Act as Novel Biomarkers in Colon Cancer.

OBJECTIVE: The Grainyhead-like (GRHL) genes family were reported to participate in the development of a number of diseases. This study was designed to investigate the role of GRHL genes family in colon cancer (CC). METHODS: In this study, the transcriptional levels of GRHL genes family in patients with CC from GEPIA were explored. Meanwhile, the immunohistochemical data of the GRHL genes family were also obtained in the HPA database. Additionally, we re-identified the mRNA of these genes via real-time PCR. Furthermore, the association between the levels of GRHL genes and stage plot as well as survival condition including overall survival and disease-free survival of patients with CC was analyzed. Finally, by transfecting with specific-siRNA, clone formation assay was performed to observe the role of GRHL genes family in the proliferation of SW480 human colon cancer cells. RESULTS: We found that the mRNA and protein levels of GRHL1, GRHL2 and GRHL3 were significantly higher in CC tissues than in normal colon tissues. Additionally, GRHL1, GRHL2 and GRHL3 were significantly associated with the stages of CC. The Kaplan-Meier plotter showed that the low levels of GRHL1, GRHL2 and GRHL3 conferred a better overall survival of patients with CC while the high levels of GRHL1 and GRHL3 were associated with poor disease-free survival. Knockdown of GRHL1, GRHL2 and GRH L3 siHgnificantly inhibited the ability of colony formation of human colon cancer cells. CONCLUSION: Our study demonstrated that GRHL genes are involved in the prognosis and survival in patients with CC, the inhibition of which may suppress the proliferation of colon cancer cells.