Esophageal squamous cell carcinoma (ESCC) is the most common type of esophageal cancer in China and the 5-year mortality rate is up to 70%. Studies on the ESCC genetic landscape are needed to further explore clinical therapeutic strategies. In this study, we evaluated the genetic landscape of ESCC to aid the search for clinical therapeutic strategies.

A total of 225 ESCC patients were enrolled in this study. Deep sequencing of 450 cancer genes was performed on formalin-fixed paraffin-embedded tumor biopsies and matched blood samples from patients. Tumor mutational burden (TMB) was calculated using an algorithm developed in-house.

Our results showed that the most commonly mutated genes in ESCC were

(96%),

(46%),

(44%),

(44%),

(44%),

(31%),

(26%),

(24%),

(18%),

(16%), and

(16%). We found that TMB correlated with patient drinking status. We identified mutations associated with sex, early ESCC, high TMB, and metastasis lymph nodes.

mutations associated with sex (

= 0.035), tumor stage (

= 0.016), high TMB (

= 0.0072), and overall survival of patients (

= 0.0026).

mutations associated with high TMB (

= 0.0016) and metastasis-positive lymph nodes (

= 0.027). These results suggested that

and

could be potential prognosis biomarkers for Chinese patients with ESCC. We also found that the number of positive lymph nodes was associated with disease-free survival. Clinical target gene analysis indicated that nearly half of Chinese ESCC patients might benefit from treatment with gene-specific target drugs.

Our study revealed the ESCC mutational landscape in 225 Chinese patients and uncovered the potential prognosis biomarker for Chinese patients with ESCC.

Our study revealed the ESCC mutational landscape in 225 Chinese patients and uncovered the potential prognosis biomarker for Chinese patients with ESCC.

Interleukin-1 receptor-associated kinase 1 (IRAK1) was shown to contribute to a variety of cancer-related processes. However, the function of IRAK1 in hepatocellular carcinoma (HCC) pathogenesis has not been investigated in detail.

IRAK1 expression in HCC was examined by immunohistochemistry, qRT-PCR, and Western blot assays. In addition, Huh7 and Hep3B cells were transfected with IRAK1 siRNAs and/or a NOD-like receptor family pyrindomain containing 3 (NLRP3) plasmid. Western blot, EdU staining, and Transwell assays were performed to determine changes of apoptosis, proliferation, migration, and invasion in HCC cells. this website Moreover, changes in the expression of proteins involved in the MAPKs/NLRP3/IL-1β pathway were confirmed by Western blotting.

IRAK1 was found to be highly upregulated in HCC tissues and cells. Knockdown of IRAK1 signaling prevented the proliferation, invasion, migration, epithelial-mesenchymal transition (EMT) of HCC cells. Mechanistically, we found that activation of the MAPKs/NLRP3/IL-1β pathway could be markedly suppressed by IRAK1 knockdown in HCC cells. Furthermore, our data showed that NLRP3 could partially reverse the reduced aggressive biological behaviors of HCC cells which were caused by RAK1 knockdown.

Knockdown of

prevented HCC progression by inhibiting the ability of NLRP3 to block the MAPKs/IL-1β pathway, suggesting that approach as a strategy for treating HCC.

Knockdown of IRAK1 prevented HCC progression by inhibiting the ability of NLRP3 to block the MAPKs/IL-1β pathway, suggesting that approach as a strategy for treating HCC.

Immune checkpoint inhibitor (ICI) monotherapy has limited efficacy in patients with non-small cell lung cancer (NSCLC) and brain metastases (BMs). With the wide use of ICI-based combinations, the efficacy of different ICI combination strategies in patients with NSCLC and BMs needs to be further elucidated.

We retrospectively reviewed 526 patients with non-small cell lung cancer (NSCLC) treated with ICIs from January 2016 to December 2019 in the Shanghai Pulmonary Hospital. Patients with BMs treated with ICIs were further divided into two groups those with BM prior to the ICI treatment (pBM group), and those with BM after the treatment (aBM group). We assessed intracranial progression-free survival (IPFS), systemic progression-free survival (SPFS), overall survival (OS), intracranial objective response rate (IORR), and intracranial disease control rate (IDCR).

We found 77 patients out of 526 with BMs; 69 presented the BMs prior to the ICI treatments and 8 showed BMs after the ICI treatments. In the pBM gchemotherapy demonstrated survival benefits over ICI monotherapy in patients with NSCLCs and BMs.

Gastric cancer (GC) is a type of malignant cancer with a poor prognosis. The iron’s metabolism plays an important role in the process of GC. The aim of this study was to evaluate the effectiveness of

, associated with iron metabolism, in predicting the prognosis of GC patients.

We analyzed genes related to iron metabolism of gastric cancer mRNA-seq data from TCGA database. We identified an iron metabolism-related

as an independent prognostic factor using univariate and multivariate Cox regression analysis.

Further research showed that

was related with many pathways involved in the process of gastric cancer, and the expression was associated with diverse cancer-infiltrating immune cells. The expression of

was associated with T (Topography).

We validated that

associated with iron metabolism could serve as a prognostic biomarker for GC patients.

We validated that SLC22A17 associated with iron metabolism could serve as a prognostic biomarker for GC patients.

Chemo-resistance is still considered one of the key factors in the mortality of ovarian cancer. In this work, we found that ubiquitin-conjugating enzyme E2 N (UBE2N) is downregulated in paclitaxel-resistant ovarian cancer cells. It suggests UBE2N to be critical in the regulation of paclitaxel sensitivity in ovarian cancer.

Ovarian cancer cells with stably overexpressed UBE2N were injected into nude mice to assess tumor growth and paclitaxel sensitivity in vivo. The MTT assay was applied to observe the effect of UBE2N expression on paclitaxel sensitivity. A real-time PCR array, specific for human cancer drug resistance, was used to examine the potential downstream target genes of UBE2N. The expression of UBE2N and potential downstream target genes was determined by Western blotting. The analysis of Gene Ontology and protein-protein interactions of these differentially expressed genes (DEGs) was performed using online tools. To evaluate the prognostic value of hub genes expression for ovarian cancer patients treated with paclitaxel, we applied the online survival analysis tool.