No abstract

Gastric cancer (GC) is a common tumour that affects humans worldwide, is highly malignant and has a poor prognosis. Small extracellular vesicles (sEVs), especially exosomes, are nanoscale vesicles released by various cells that deliver bioactive molecules to recipient cells, affecting their biological characteristics, changing the tumour microenvironment and producing long-distance effects. In recent years, many studies have clarified the mechanisms by which sEVs function with regard to the initiation, progression, angiogenesis, metastasis and chemoresistance of GC. These molecules can function as mediators of cell-cell communication in the tumour microenvironment and might affect the efficacy of immunotherapy. Due to their unique physiochemical characteristics, sEVs show potential as effective antitumour vaccines as well as drug carriers. In this review, we summarize the roles of sEVs in GC and highlight the clinical application prospects in the future.

At present, it is commonly believed that tRFs and tiRNAs are formed by the specific and selective shear of tRNAs under certain pressure stimulation, rather than by random degradation of tRNA. tRFs and tiRNAs have been reported to contribute to the biological process of a variety of human cancers. However, the evidence for the mechanisms of tRFs and tiRNAs in the occurrence and development of gastric cancer (GC) is still insufficient. Here, we aimed to explore the carcinogenic roles of tRFs and tiRNAs in GC with RNA-sequencing technique, and found a novel 3’tRNA-derived fragment tRF-Val was significantly upregulated in GC tissues and cell lines. tRF-Val expression was positively correlated with tumor size and the depth of tumor invasion in GC tissues. Functionally, tRF-Val promoted proliferation and invasion, and inhibited apoptosis in GC cells. Mechanistically, tRF-Val directly bound to the chaperone molecule EEF1A1, mediated its transport into the nucleus and promoted its interaction with MDM2 (a specific p53 E3 ubiquitin ligase), thus inhibiting the downstream molecular pathway of p53 and promoting GC progression. These findings provided a new potential therapeutic target for GC and a new explanation for the occurrence of GC.

Immune checkpoint inhibitor (ICI) therapy has achieved remarkable clinical benefit in melanoma and non-small cell lung cancer (NSCLC). Tumor mutational signatures are the fingerprints of endogenous and exogenous factors that have acted throughout tumorigenesis and heterogeneity; however, their association with immune response in ICI-treated samples remains unclear. Here, we leveraged whole-exome sequencing (WES)-based mutational profiles combined with clinicopathologic characteristics from melanoma and NSCLC datasets to examine whether tumor genomic features contribute to clinical benefit of ICI treatment. Mutational data acquired from targeted next-generation sequencing (NGS) assays (MSK-IMPACT panels) were also employed for further corroboration. A mutational signature (known as age-related clock-like processing) characterized by enrichment of C>T mutations at NpCpG trinucleotides were identified to be associated with a worse prognosis and lower tumor mutation load (TML) in both WES and targeted NGS immunotherapy cohorts. We also analyzed gene transcriptomic profiles and identified immune regulation-related gene pathways that were significantly altered in samples with different clock-like signature grouping. Leucocyte subset analysis further revealed that clock-like signature was associated with the reduction of cytotoxic cell infiltration and elevation of regulatory T cells. Overall, our work re-annotated that the age-related clock-like signature was associated with worse prognosis and lower immune activity, offering opportunities to stratify patients into optimal immunotherapy plans based on genomic subtyping.

Background: With the increasing prevalence of Siewert type Ⅱ adenocarcinoma of the esophagogastric junction (EGJ), the optimal surgical treatment is not universally agreed. This meta-analysis compares the safety and efficacy between the transhiahtal (TH) approach and the transthoracic (TT) approach. Methods: A systematic and electronic search of several databases was performed up to June 2020. The Newcastle-Ottawa scale was used to evaluate article quality and funnel plots were created to identify potential publication bias. The random-effects model was used when significant heterogeneity was identified. Results: In total, nine retrospective studies and two randomized controlled trials (RCTs) involving 2331 patients were included. Decreased intraoperative blood loss, shorter hospital stay, lower incidence of pulmonary complications, and longer 3-year overall survival were observed in the TH group. There were no significant differences concerning duration of surgery, R0 resection rate, number of dissected lymph nodes, perioperative mortality and morbidity rate, abdominal complication rate, or anastomotic leak rate. With regard to 5-year overall survival, a potential benefit may be achieved with the TH approach, which requires further confirmation. Conclusion: In terms of surgery-related and long-term outcomes, the TH approach may be more appropriate for Siewert type Ⅱ adenocarcinoma of EGJ, especially for esophagus invasion ≤4 cm.

Organoids are established through in vitro 3D culture, and they can mimic the structure and physiological functions of organs or tissues in vivo. Organoids have attracted much attention in recent years. They can provide a reliable technology platform for cancer research and treatment and are a valuable preclinical model for academic research and personalized medicine. A number of studies have confirmed that organoids have great application prospects in new drug development, drug screening, tumour mechanism research, and precision medicine. In this review, we mainly focus on recent advances in the application of organoids in cancer research. We also discussed the opportunities and challenges facing organoids, hoping to indicate directions for the development of organoids in the future.

BackgroundNF1(Neurofibromatosis type 1) is an autosomal dominant genetic disorder. Patients with NF1 have an increased risk of developing benign or malignant tumours, such as gastrointestinal stromal tumours (GISTs). However, the coexistence of NF1, GIST and colon cancer is very rare, and few cases have been reported in the literature.Case presentationWe admitted a case of a 64-year-old man with type 1 neurofibromatosis, GISTs, and ascending colon cancer. This case was characterized by café-au-lait macules, discrete cutaneous neurofibromas, nodular neurofibromas, multiple jejunal tumours, and ascending colon cancer. Laparoscopic exploration revealed ascending colon cancer and multiple jejunal tumours. Laparoscopic right hemicolectomy and local excision of the jejunal tumours were performed successfully. The pathological results confirmed moderate differentiated adenocarcinoma of the ascending colon with multiple jejunal GISTs (low risk, very low risk). Moreover, the immunohistochemistry results of multiple jejunal GISTs suggest that NF1 is positive. Whole-exome sequencing (WES) of colon cancer revealed mutations in more than 20 genes, including KRAS, PIK3CA, APC, SMAD4, etc. The results of whole-exome sequencing (WES) of jejunal GISTs revealed an NF1 mutation and no KIT or PDGFR gene mutation.ConclusionWe report a rare case of simultaneous NF1, GIST and colon adenocarcinoma. For patients with NF1, benign and/or malignant tumours are often combined. Therefore, these patients should undergo regular physical examinations so that early detection and early treatment can be achieved.

Background and aims: The benefit of lateral pelvic lymph node dissection (LPLD) for locally advanced rectal cancer remains controversial. This meta-analysis aimed to evaluate the prognostic value of LPLD in patients with locally advanced rectal cancer. Methods:We performed a systematic search in PubMed, Embase, and the Cochrane Library for publications comparing radical resection plus LPLD (LPLD group) with single radical resection (non-LPLD group) for locally advanced rectal cancer. A total of 15 studies satisfied our inclusion criteria and were assessed. Random-effects and fixed-effects meta-analytical models were used where indicated, and between-study heterogeneity was assessed.Results: LPLD significantly increased grade 3-4 postoperative complications (odds ratio[OR]1.44, 95% CI 1.03-2.02; P = 0.03) compared with non-LPLD. There were no significant differences in 5-y overall survival (hazard ratio = 0.90, 95% CI 0.77-1.05; P = 0.17), 5-y diseasefree survival (hazard ratio 1.12, 95% CI 0.60-2.09; P = 0.73), local recurrence (OR 0.89, 95% CI 0.53-1.51; P = 0.68) or distant recurrence (OR 0.85, 95% CI 0.64-1.12; P = 0.24). Conclusions:We found that LPLD significantly increased grade 3-4 postoperative complications but did not increase 5-y overall survival or 5-y disease-free survival compared with single radical resection for locally advanced rectal cancer. Furthermore, it did not decrease the local recurrence or distant recurrence rates. Thus, more multicenter large-scale randomized controlled trials should be conducted to further explore whether the long-term survival benefits of LPLD truly exist.