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Alternative splicing, regulated by DEAD‐Box Helicase (DDX) families, plays an important role in cancer. However, the relationship between the DDX family and cancer has not been fully elucidated. In the present study, we identified a candidate oncogene DDX56 on Ch.7p by a bioinformatics approach using The Cancer Genome Atlas (TCGA) dataset of colorectal cancer (CRC). DDX56 expression was measured by RT‐qPCR and immunochemical staining in 108 CRC patients. Clinicopathological and survival analyses were carried out using three CRC datasets. Biological roles of DDX56 were explored by gene set enrichment analysis (GSEA), and cell proliferation in vitro and in vivo, cell cycle assays, and using DDX56‐knockdown or overexpressed CRC cells. RNA sequencing was carried out to elucidate the effect of DDX56 on mRNA splicing. We found that DDX56 expression was positively correlated with the amplification of DDX56 and was upregulated in CRC cells. High DDX56 expression was associated with lymphatic invasion and distant metastasis and was an independent poor prognostic factor. In vitro analysis, in vivo analysis and GSEA showed that DDX56 promoted proliferation ability through regulating the cell cycle. DDX56 knockdown reduced intron retention and tumor suppressor WEE1 expression, which functions as a G2‐M DNA damage checkpoint. We have identified DDX56 as a novel oncogene and prognostic biomarker of CRC that promotes alternative splicing of WEE1. We identified DDX56 as a novel oncogene on chromosome 7p and a prognostic biomarker of colorectal cancer (CRC). DDX56 can induce oncogenic splicing abnormalities of the G2‐M cell cycle checkpoint gene WEE1 which contributes to the inhibition of proliferation and cell cycle progression.

BackgroundWhether laparoscopic surgery after prior abdominal surgery (PAS) is safe and feasible for colorectal cancer (CRC) remains controversial. The present study aimed to evaluate the impact of PAS on short-term outcomes following laparoscopic CRC surgery.MethodsWe performed retrospective analysis used propensity score-matched analysis to reduce the possibility of selection bias. Participants comprised 1284 consecutive patients who underwent elective laparoscopic CRC surgery between 2010 and 2020. Patients were divided into two groups according to PAS. Patients with PAS were then matched to patients without these conditions. Short-term outcomes were evaluated between groups in the overall cohort and matched cohort, and risk factors for conversion to laparotomy and severe postoperative complications were analyzed.ResultsAfter propensity score matching, we enrolled 762 patients (n = 381 in each group). Before matching, significant group-dependent differences were observed in sex, age, primary tumor site, pathological (p) T stage, and type of procedure. No significant difference was found between groups in terms of rate of conversion to laparotomy, estimated blood loss, rate of extended resection, length of postoperative stay, and postoperative complications. After matching, estimated operative time was significantly longer in the PAS group (p = 0.01). Significant differences were found between groups in terms of reason for conversion to laparotomy. Multivariate analyses identified significant risk factors for conversion to laparotomy as pT stage ≥ 3 (odds ratio [OR] 2.36; 95% confidence interval [CI] 1.05–5.26) and body mass index ≥ 25 kg/m2 (OR 3.56; 95% CI 1.07–11.7). Multivariate analyses identified rectum in the primary tumor site as the only significant risk factor for severe postoperative complications (OR 2.37; 95% CI 1.08–5.20).ConclusionsLaparoscopic CRC surgery after PAS showed acceptable short-term outcomes compared to Non-PAS. The laparoscopic approach appears safe and feasible for CRC regardless of whether the patient has a history of PAS.

BackgroundSerum microRNAs (miRNAs) have been recognized as potential stable biomarkers for various types of cancer. Considering the clinical applications, there are certain critical requirements, such as minimizing the number of miRNAs, reproducibility in a longitudinal clinical course, and superiority to conventional tumor markers, such as carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9. This study aimed to identify serum miRNAs that indicate the recurrence of colorectal cancer (CRC), surpassing inter-tumor heterogeneity.MethodsWe conducted an analysis of 434 serum samples from 91 patients with CRC and 71 healthy subjects. miRNAs were obtained from Toray Co., Ltd, and miRNA profiles were analyzed using a three-step approach. miRNAs that were highly expressed in patients with CRC than in the healthy controls in the screening phase, and those that were highly expressed in the preoperative samples than in the 1-month postoperative samples in the discovery phase, were extracted. In the validation phase, the extracted miRNAs were evaluated in 323 perioperative samples, in chronological order.ResultsA total of 12 miRNAs (miR-25-3p, miR-451a, miR-1246, miR-1268b, miR-2392, miR-4480, miR-4648, miR-4732-5p, miR-4736, miR-6131, miR-6776-5p, and miR-6851-5p) were significantly concordant with the clinical findings of tumor recurrence, however their ability to function as biomarkers was comparable with CEA. In contrast, the combination of miR-1246, miR-1268b, and miR-4648 demonstrated a higher area under the curve (AUC) than CEA. These three miRNAs were upregulated in primary CRC tissues.ConclusionWe identified ideal combinatorial miRNAs to predict CRC recurrence.

The accurate and early diagnosis and classification of cancer origin from either tissue or liquid biopsy is crucial for selecting the appropriate treatment and reducing cancer-related mortality. Here, we established the CAncer Cell-of-Origin (CACO) methylation panel using the methylation data of the 28 types of cancer in The Cancer Genome Atlas (7950 patients and 707 normal controls) as well as healthy whole blood samples (95 subjects). We showed that the CACO methylation panel had high diagnostic potential with high sensitivity and specificity in the discovery (maximum AUC = 0.998) and validation (maximum AUC = 1.000) cohorts. Moreover, we confirmed that the CACO methylation panel could identify the cancer cell type of origin using the methylation profile from liquid as well as tissue biopsy, including primary, metastatic, and multiregional cancer samples and cancer of unknown primary, independent of the methylation analysis platform and specimen preparation method. Together, the CACO methylation panel can be a powerful tool for the classification and diagnosis of cancer.

The spliceosome pathway, including Splicing Factor 3b Subunit 4 (SF3B4), plays an important role in carcinogenesis and progression in various cancers; however, the clinical relevance of SF3B4 in esophageal squamous cell carcinoma (ESCC) remains unknown. SF3B4 expression was evaluated by real-time reverse transcription polymerase chain reaction in 80 ESCC patients. In order to explore the mechanism of SF3B4 in ESCC, the mRNA expression and copy number of SF3B4 were obtained from TCGA and we also implemented gene set enrichment analysis (GSEA). The high SF3B4 expression group (n=33) showed significantly more lymphatic permeation and poorer prognosis than the low SF3B4 expression group (n=47). GSEA revealed that high SF3B4 expression was correlated with genes associated with the transcription factor E2F and the G /M checkpoint. SF3B4 expression was positively correlated with SF3B4 DNA copy number. Over-expression of SF3B4 may play a crucial role in the lymphatic progression of ESCC.

Circulating microRNAs (miRs) in blood have been highlighted as diagnostic, prognostic and predictive biomarkers for \"Precision medicine\". This study aimed to explore the possibility of using circulating precursor miRs (pre-miRs) as clinical biomarkers of recurrence in breast cancer. We performed miR microarray analyses of circulating miRs in blood from patients with or without recurrence of breast cancer and identified miR-488-5p as a recurrence-related miR. Then, the expression levels of pre-miR-488 or miR-488-5p were measured by RT-qPCR and the clinicopathological and prognostic significance of circulating pre-miR-488 was assessed in the blood of breast cancer patients. A positive correlation was noted between pre-miR-488 and miR-488-5p expression in blood. In 330 cases of surgically-treated breast cancer, high expression of circulating pre-miR-488 was an independent poor prognostic factor for recurrence-free survival. Circulating pre-miR-488 expression could be a novel prognostic biomarker for predicting recurrence in breast cancer patients.

INTRODUCTION: Pancreatic mucinous cystic neoplasm (MCN) is a cystic tumor of the pancreas typically located in the pancreatic body or tail in middle-aged women. However, MCN rupture is rare. This report describes a case of MCN with spontaneous rupture during follow-up.CASE PRESENTATION: The patient was a 34-year-old woman. Contrast-enhanced computed tomography (CECT) and magnetic resonance imaging (MRI) revealed a 130 mm multifocal cyst in the pancreatic tail. The cyst, characterized by multiple septa and cyst-in-cyst structures, was diagnosed as an MCN. Initially, the patient opted for periodic follow-ups instead of surgical resection. After a gradual increase in cyst size, surgery was scheduled approximately 1 year later. Two days before the scheduled surgery, the patient experienced unexplained lower abdominal pain. Moreover, CECT revealed a shrinking cystic mass in the pancreatic tail along with the presence of ascites, leading to a diagnosis of spontaneous rupture of the pancreatic cyst. No peritonitis was detected, and a distal pancreatectomy was performed 2 days after admission. Pathological examination confirmed that the pancreatic cyst was a noninvasive mucinous cystadenocarcinoma. The abdominal cavity contained large amounts of turbid ascites with neutrophils but no bacterial growth. Strong inflammatory changes were noted at the cyst wall disruption site. Despite the development of a pancreatic fistula (ISGPF Grade BL, Clavien–Dindo Grade II), the patient was discharged from the hospital on postoperative day 16 and remained alive and recurrence-free for 18 months after surgery.CONCLUSION: Spontaneous rupture of an MCN is rare. In this study, we report our case and review previously published cases of MCN rupture. We also discuss the potential causes of the spontaneous rupture in our case.

Background Concomitant multiple myeloma (MM) and other primary malignancies is rare. Therefore, the treatment outcomes of patients with these conditions have not been well discussed. Lenalidomide is an oral thalidomide analog drug used for MM. Recently, the antitumor effect of lenalidomide has been gaining attention, and lenalidomide has been applied for managing solid tumors. The current case showed the treatment course of a patient treated with lenalidomide for concomitant MM and colon cancer with peritoneal dissemination. Case presentation A 74-year-old female patient receiving treatment for MM was diagnosed with mucinous adenocarcinoma of the transverse colon. The patient was clinically diagnosed with stage IIIC T4aN2M0 disease. Subsequently, laparoscopic colectomy with lymph node dissection was planned. However, intraperitoneal observation revealed peritoneal dissemination that had sporadically and widely spread. Therefore, palliative partial colectomy was performed to prevent future hemorrhage or obstruction. The patient was discharged on the 10th postoperative day without postoperative complication. Based on the patient’s preference, lenalidomide was continually administered for MM without systemic chemotherapy. The patient survived for > 36 months without any signs of tumor progression. Conclusion The current case first showed the treatment course of concomitant MM and colon cancer. The antitumor effect of lenalidomide can possibly contribute to 3-year progression-free survival in patients with mucinous adenocarcinoma of the colon with peritoneal dissemination.

Human oxidation resistance 1 (OXR1) was identified as a protein that decreases genomic mutations in Escherichia coli caused by oxidative DNA damage. However, the mechanism by which OXR1 defends against genome instability has not been elucidated. To clarify how OXR1 maintains genome stability, the effects of OXR1-depletion on genome stability were investigated in OXR1-depleted HeLa cells using gamma-rays (γ-rays). The OXR1-depleted cells had higher levels of superoxide and micronucleus (MN) formation than control cells after irradiation. OXR1-overexpression alleviated the increases in reactive oxygen species (ROS) level and MN formation after irradiation. The increased MN formation in irradiated OXR1-depleted cells was partially attenuated by the ROS inhibitor N-acetyl-L-cysteine, suggesting that OXR1-depeletion increases ROS-dependent genome instability. We also found that OXR1-depletion shortened the duration of γ-ray-induced G2/M arrest. In the presence of the cell cycle checkpoint inhibitor caffeine, the level of MN formed after irradiation was similar between control and OXR1-depleted cells, demonstrating that OXR1-depletion accelerates MN formation through abrogation of G2/M arrest. In OXR1-depleted cells, the level of cyclin D1 protein expression was increased. Here we report that OXR1 prevents genome instability by cell cycle regulation as well as oxidative stress defense.

INTRODUCTION: Desmoplastic small round cell tumor (DSRCT) is a highly malignant sarcoma and an extremely rare tumor, predominantly found in the abdominal and pelvic regions. Here, we report the case of a patient who underwent surgical treatment for multiple desmoplastic round cell tumor in the intestine.CASE PRESENTATION: A 38-year-old male patient visited our hospital after a health check revealed positive occult blood in his stool and a colonoscopy revealed tumors in descending colon and sigmoid colon. Biopsy results revealed poorly differentiated adenocarcinoma. Chest and abdominal enhanced computed tomography revealed 3 tumors from descending colon to sigmoid colon and numerous peritoneal disseminations. Based on these findings, we diagnosed multiple colon cancers and performed a laparoscopic left hemicolectomy. Hematoxylin–Eosin (H&E) staining showed that in all tumors, atypical cells with large and small swollen nuclei formed irregular solid nests of various sizes against a background of extensive desmoplastic or myxomatous stroma. Immunohistochemistry showed that tumor cells were AE1/3 (+), S-100 (–), Desmin (–), WT1 (–). Genetic analysis detected the Ewing’s sarcoma and Wilms tumor fusion gene at another inspection agency. Histopathological examination identified desmoplastic small round cell tumor. The patient was discharged on the 19th postoperative day without postoperative complications. He will undergo chemotherapy at another hospital.CONCLUSIONS: We experienced a very rare case of DSRCT. DSRCT is a fatal disease that primarily affects adolescent and young adult males. Currently, there is no proven treatment. More case reports are essential to improve management of this disease.