Background: The accuracy of lymph node ratio (LNR) as a prognostic index remains to be proven for gastric cancer patients after neoadjuvant chemotherapy (NACT). This study sought to investigate the prognostic value of LNR in locally advanced gastric cancer (LAGC) patients after NACT.Methods: LAGC patients with clinical TNM stages 2–3, Her2(−), and Eastern Cooperative Oncology Group, scores 0–2 are routinely scheduled with NACT. Patients with LAGC after NACT and surgical operation between January 2012 and October 2020 were retrospectively reviewed. The correlation between LNR and survival was investigated.Results: Overall, 148 patients were enrolled: 103 with low-LNR (LNR ≤ 30%) and 45 with high-LNR (LNR > 30%). Approximately, 50.5% and 24.4% patients responded to NACT at the primary site in the low-LNR and high-LNR groups, respectively. The overall survival (OS) and progression-free survival (PFS) of low-LNR group were considerably better than those of high-LNR group (3-year OS: 81.9% vs 18.5%,P< 0.001; 3-year PFS: 72.6% vs 13.5%,P< 0.001). In the low-LNR group, OS and PFS were superior in patients with tumor regression grade (TRG) 0–2 than in those with TRG 3 (3-year OS: 89.2% vs 73.2%,P= 0.086; 3-year PFS: 80.3% vs 66.5%,P= 0.036). In association with OS and PFS, the degree of tumor differentiation, TRG, and LNR were identified as predictive factors, and LNR was identified as the independent prognostic factor in univariate and multivariate analyses, respectively.Conclusions: LNR is a prospective index of prognosis in patients with LAGC after NACT.

Retroperitoneal liposarcoma (RPLS) is a rare tumor, especailly those over 20 kg that are called “giant liposarcoma," whose characteristics and treatments remain relatively unknown. Herein, we report a giant RPLS measuring 65 × 45 × 30 cm in diameter and 31 kg in weight, which we successfully performed complete excision through interdisciplinary cooperation. The patient had an uneventful postoperative course and was discharged without complications. Afterwards he underwent radiotherapy and had no evidence of tumor recurrence or symptoms of metastasis at 3-month CT scan and 8-month follow-up. We also first review the 13 cases reported in literature published in PubMed regarding giant RPLS. Giant RPLS commonly occurs in adults aged 40–60 y and presents atypical clinical manifestations. CT scan is the most useful examination and preoperative biopsy is controversial. Complete surgical resection still remains the principal treatment. Giant RPLS can also be removed, even reach to R0 excision, by a multidisciplinary team in a specialized center after meticulous planning even though its gigantic tumor size. Local radiotherapy following surgery may improve the rate of recurrence. Besides, closely follow-up and routine examinations are required.

Tumor metastasis severely limits the prognosis of gastric cancer patients. RNA-binding proteins (RBPs) are crucial in tumor metastasis, yet there is limited research into their involvement in gastric cancer. Here, we found that ESRP1, a RBP specific in epithelial cells, is important in regulating the metastasis of gastric cancer cells. ESRP1 is negatively correlated with distant metastasis and lymph node metastasis in gastric cancer patients. And we demonstrated that ESRP1 inhibit migration and invasion of gastric cancer in vitro and in vivo. Mechanistically, ESRP1 promotes exon 11 alternative splicing of CLSTN1 pre-mRNA. The post-splicing short CLSTN1 stabilizes the Ecadherin/β-catenin binding structure, and promotes β-catenin protein ubiquitination and degradation, thereby inhibiting the migration and invasion of gastric cancer cells. Our study highlights the role of ESRP1 in regulating metastasis of gastric cancer and extends its mechanism. These results provide a possibility for ESRP1 and CLSTN1 to become therapeutic targets for metastasis of gastric cancer.

Imatinib mesylate (IM) has revolutionized the treatment of gastrointestinal stromal tumor (GIST). However, most patients inevitably acquire IM resistance. Second- and third-line treatments exhibit modest clinical benefits with a median time to disease progression of 4 to 6 months, highlighting the urgency for novel therapeutic approaches. Here, we report that the expression of BCL6, a known oncogenic driver and transcriptional repressor, was significantly induced in GIST cells following IM treatment. Elevated BCL6 levels suppressed apoptosis and contributed to IM resistance. Mechanistically, BCL6 recruited SIRT1 to the TP53 promoter to modulate histone acetylation and transcriptionally repress TP53 expression. The reduction in p53 subsequently attenuated cell apoptosis and promoted tolerance of GIST cells to IM. Concordantly, treatment of GIST cells showing high BCL6 expression with a BCL6 inhibitor, BI-3802, conferred IM sensitivity. Furthermore, BI-3802 showed striking synergy with IM in IM-responsive and IM-resistant GIST cells in vitro and in vivo. Thus, these findings reveal a role for BCL6 in IM resistance and suggest that a combination of BCL6 inhibitors and IM could be a potentially effective treatment for GIST. Significance: BCL6 drives resistance to imatinib by inhibiting p53-mediated apoptosis and can be targeted in combination with imatinib to synergistically suppress tumor growth, providing a therapeutic strategy for treating gastrointestinal stromal tumor.

The drug 5-fluorouracil (5-Fu) is the critical composition of colorectal cancer (CRC) treatments. Prognostic and predictive molecular biomarkers for CRC patients (CRCpts) treated with 5-Fu-based chemotherapy can provide assistance for tailoring treatment approach. Here, we established a molecular biomarker of 5-Fu resistance derived from colorectal cancer organoids (CRCOs) for predicting the survival of CRCpts. Forty-one CRCO cultures were generated from 50 CRC tumor tissues after surgery (82%). The following experiments revealed a great diversity in drug sensitivity for 10 μM 5-Fu treatment tested by using organoid size change. Fourteen cases (34.1%) were 5-Fu sensitive and the other 27 (65.9%) were resistant. Then, differentially expressed genes (DEGs) associated with 5-Fu resistance were outputted by transcriptome sequencing. In particular, DEGs were generated in two comparison groups: 1) 5-Fu sensitive and resistant untreated CRCOs; 2) CRCOs before 5-Fu treatment and surviving CRCOs after 5-Fu treatment. Some molecules and most of the pathways that have been reported to be involved in 5-Fu resistance were identified in the current research. By using DEGs correlated with 5-Fu resistance and survival of CRCpts, the gene signature and drug-resistant score model (DRSM) containing five molecules were established in The Cancer Genome Atlas (TCGA)-CRC cohort by least absolute shrinkage and selection operator (LASSO) regression analysis and 5-fold cross-validation. Multivariate analysis revealed that drug-resistant score (DRS) was an independent prognostic factor for overall survival (OS) in CRCpts in TCGA-CRC cohort (P < 0.001). Further validation results from four Gene Expression Omnibus (GEO) cohorts elucidated that the DRSM based on five genes related to 5-Fu chemosensitivity and developed from patient-derived organoids can predict survival of CRCpts. Meanwhile, our model could predict the survival of CRCpts in different subgroups. Besides, the difference of molecular pathways, tumor mutational burden (TMB), immune response-related pathways, immune score, stromal score, and immune cell proportion were dissected between DRS-high and DRS-low patients in TCGA-CRC cohort.

Rationale: Desmoplastic small round cell tumor (DSRCT) is a rare malignant tumor with poor prognosis, usually involving the peritoneum. There are currently no standardized treatment approaches. This study helped to further advance our understanding of DSRCT, and help to guide therapy. Patient concerns: The patient, a 19-year-old male, presented with left-sided back pain with no obvious cause and occasional abdominal pain, and underwent abdominal electron computed tomography examination in our hospital suggesting consideration of small bowel mesenchymal tumor with possible multiple implantation metastasis in the abdominopelvic cavity. Diagnoses: After surgical treatment, the pathology report suggested a DSRCT, and immunohistochemistry and fluorescence in situ hybridization revealed EWSR1-WT1 gene rearrangement. Lung computer tomography and abdominal magnetic resonance imaging performed half a month later showed multiple solid nodules on the proximal septal surface of the right lung base, right posterior cardiac/right anterior inferior vena cava nodules, and multiple nodules in the abdominopelvic cavity, omenta, peritoneum, and around the liver or liver, all of which were considered as metastatic foci. Interventions and outcomes: Patient received 5 cycles of chemotherapy after surgery. The review results showed a smaller size than before. Currently, he continues to receive treatment. Lessons: The reported case has raised awareness of the importance of DSRCT in the treatment of chemotherapy, including its role in the differential diagnosis of abdominal tumors.