BACKGROUND:The aim of this study was to investigate the expression level of martrilin-3 (MATN3) in patients with gastric adenocarcinoma (GAC) and to investigate the prognostic significance of MATN3. MATERIAL AND METHODS:Gene Expression Omnibus (GEO) ...

Background: Immune checkpoint inhibitors (ICIs) have drastically shifted the current landscape toward a wide variety of malignancies. However, ICIs are interrupted owing immune‐related adverse events (irAEs), therapy completion, and disease progression. The risk–benefit of rechallenged ICIs remains inconclusive. Herein, a systematic review and meta‐analysis were conducted to evaluate the safety and efficacy of ICI rechallenge in the treatment of advanced solid tumor.Methods: PubMed, Web of Science, Embase, and Cochrane Library were searched to analyze the efficacy and safety of ICI rechallenge. The study protocol was approved by the PROSPERO International Register of Systematic Reviews (CRD42022372222). The last updated search date was March 2, 2024. Objective response rate (ORR), disease control rate (DCR), overall survival (OS), and incidence rates of all‐ and high‐grade irAEs were evaluated.Results: A total of 41 retrospective studies comprising 2343 patients were ultimately enrolled for qualitative and quantitative assessments. A total of 1200 (51.2%) individuals were male and the median age was 66 years (range 18–97 years). The majority of the tumors was lung cancer (n = 898, 38.3%). The occurrence rates of all‐grade and high‐grade (grade 3 or 4) irAEs between initial and readministration ICIs were not significantly different (all‐grade: OR, 0.75, 95% CI: 0.39–1.45, p = 0.40; I² = 87%; high‐grade: OR, 0.96, 95% CI: 0.62–1.49, p = 0.87, I² = 65%). ICIs restart presented a decreased ORR and DCR compared to initial ICI administration (ORR: OR, 0.36, 95% CI: 0.23–0.56, p < 0.00001; I² = 67%; DCR: OR, 0.62, 95% CI: 0.43–0.89, p = 0.010; I² = 53%). Seven studies with 513 patients for survival analysis revealed a nonsignificant difference in OS between the ICIs rechallenge and discontinuation cohorts (hazard ratio [HR]: 0.68, 95% confidence interval (CI): 0.35 to 1.35, p = 0.27).Conclusion: Rechallenging immunotherapy is feasible, and patients should be carefully evaluated by a multidisciplinary team prior to initial therapy for close monitoring and assessment of the risk–benefit ratio. Therefore, prospective trials are essential to guide clinicians in the decision‐making process.PROSPERO Registration: CRD42022372222.

Previous studies have indicated that centromere protein K (CENPK) is upregulated in several cancers and related to tumorigenesis. Nevertheless, the potential function of CENPK in gastric cancer (GC) remains unknown. Here, we investigated the function of CENPK on oncogenicity and explored its underlying mechanisms in GC. Our results showed that CENPK was dramatically overexpressed in GC and was associated with poor prognosis through bioinformatics analysis. We demonstrated that CENPK is upregulated in GC tissues and cell lines. Moreover, knockdown of CENPK significantly inhibited proliferation in vitro and attenuated the growth of implanted GCs in vivo. In addition, CENPK silencing induced G1 phase cell cycle arrest and facilitated apoptosis of GC cells. KEGG pathway analysis indicated that the PI3K‐AKT signalling pathway was considerably enriched. Knockdown of CENPK decreased the expression of PI3K, p‐Akt (Ser437) and p‐GSK3β (Ser9) in GC cells, and increased the expression of PTEN. In conclusion, this study indicated that CENPK was overexpressed in GC and may promote gastric carcinogenesis through the PTEN‐PI3K‐AKT signalling pathway. Thus, CENPK may be a potential target for cancer therapeutics in GC.

Hepatitis B virus (HBV) infection has been reported to be associated with gastric cancer (GC). Nonetheless, no study has revealed the role of HBV infection in the survival of patients with GC, and the mutation profiles of HBV-infected patients with GC have never been documented. Here, we performed an updated meta-analysis and found a significantly increased risk of GC in HBV-infected individuals (sOR, 1.29; 95% CI, 1.22-1.37). Furthermore, we observed that in the Anhui area, the rate of serum HBsAg positivity (OR, 1.62; 95% CI, 1.03-2.55) was significantly higher in GC patients than in controls. Moreover, our results showed that HBV-positive patients had significantly worse disease-free survival (HR, 1.98; 95% CI, 1.39-2.82) and overall survival (HR, 1.84; 95% CI, 1.19-2.85) than HBV-negative patients. The results of Cox proportional hazards regression proved that HBV infection was an independent adverse prognostic factor in GC. Furthermore, by performing targeted-NGS, we found unique mutation profiles in HBV-infected GC samples, including five frequently mutated protein-coding genes (KMT2B, KMT2D, SOX1, FGF12, and TUBB2B). Expression and survival analyses of these genes identified three novel candidate genes that may have potential roles in GC development. Gene Ontology enrichment analysis showed that the recurrent mutations in HBV-positive GC samples were related to cell proliferation, cell migration, and transcription. Taking together, our study proved that HBV infection is an independent prognostic factor in GC patients. The unique mutation profiles of HBV-infected patients with GC open a new research direction toward the underling mechanism between HBV infection and GC.

The present study aimed to analyze the clinical characteristics and prognosis-related factors of non-small cell lung cancer (NSCLC) patients with bone metastases at the time of diagnosis. A total of 46 NSCLC patients with skeletal metastases at the time of diagnosis from Anhui Provincial Hospital and Anhui Provincial Cancer Hospital Affiliated to Anhui Medical University (Hefei, China) between February 2010 and February 2012 were investigated retrospectively. The median age was 58 years, with a range of 40‑80 years, the ratio of males and females was 2:1, and adenocarcinoma and squamous cell carcinoma accounted for 71.7 and 28.3% of cases, respectively. Furthermore, 84.8% of patients exhibited multiple skeletal metastases at more than two sites and 54.3% of patients experienced skeletal‑related events at the time of diagnosis. The median overall survival (OS) time of the patients was 237 days, and Kaplan‑Meier analysis demonstrated that patients with adenocarcinoma (P=0.002), single bone metastases (P=0.023), an Eastern Cooperative Oncology Group performance status of 0‑1 (P<0.001) or positive expression of estrogen receptor (ER)‑β (P=0.039) exhibited significantly longer survival times. Furthermore, multivariate analysis identified the following independent predictors of OS: Tumor subtype (P=0.022), the number of bone metastases (P=0.016) and an ER‑β‑positive tumor (P=0.035). In the cohort of NSCLC patients with bone metastases at the time of diagnosis, adenocarcinoma and multiple skeletal metastases were most common.