NPM1 plays an important role in the occurrence and development of leukemia and various solid tumors. This study aimed to investigate the expression of NPM1 in gastric cancer (GC) and adjacent normal tissues, study the relationship between NPM1 expression and clinicopathological characteristics in GC patients, and explore the impact of NPM1 expression on the diagnosis and prognosis of GC. We used tissue microarray immunohistochemical analysis to examine the expression level of NPM1 in GC and adjacent tissues and analyzed the relationship between NPM1 expression, clinicopathological factors, and GC prognosis. Prognostic values of NPM1 mRNA were also investigated using an online database. qRT-PCR was used to detect the expression of NPM1 mRNA in cancer and adjacent tissues. According to microarray immunohistochemical analysis and qRT-PCR results, NPM1 had a high expression in all adjacent normal tissues. Microarray immunohistochemical analyses demonstrated that the NPM1 was lowly expressed in 75.5% of GC tissues but highly expressed in 24.5% of GC tissues. qRT-PCR results showed NPM1 mRNA low expression in most GC tissues. NPM1 high expression group was associated with a better overall survival rate and disease-free survival rate than the NPM1 low expression group (p < 0.01). This result is consistent with that of the online database. The receiver operating characteristics curve showed that NPM1 was valuable in the diagnosis of GC.The assessment of NPM1 expression in GC samples may represent a useful tool for GC diagnosis and prognosis assessment.
BackgroundPediatric colorectal carcinoma (PCRC) is a rare non-embryonal tumor with an incidence of 0.1% to 1% of adults. Immune checkpoint inhibitors (ICIs) targeting programmed death-1 (PD-1) have shown significant efficacy in defective mismatch repair/Microsatellite instability-high (dMMR/MSI-H) metastatic CRC (mCRC). Although several studies have reported neoadjuvant immunotherapy (NIT) in MSI-H/dMMR non-mCRC patients, not all patients achieved pathological complete remission (pCR). There are differences between PCRC and adult colorectal carcinoma (CRC), and the role of NIT in PCRC remains to be further defined.Case presentationWe report the case of a 12-year-old child who was admitted to the hospital with abdominal pain and vomiting for more than 3 months. The child’s diagnosis was difficult and complex. He was initially diagnosed with intestinal obstruction, eventually diagnosed with a rare PCRC and identified as locally advanced colorectal cancer (LACRC) with genetic sequencing results showing MSI-H. After a thorough evaluation by clinicians, he received 4 cycles of Camrelizumab (anti-PD-1 antibody) + CapeOx (capecitabine and oxaliplatin) NIT combination chemotherapy. Repeat imaging and all tumor markers were unremarkable, and R0 resection was achieved. Postoperative pathology showed a tumor regression grade (TRG) of 0 grade determined as pCR. Postoperative review has not shown any recurrence or metastasis to date and the prognosis is good.ConclusionPCRC should improve the diagnostic efficiency to prevent misdiagnosis and miss the best time for treatment. NIT and or chemotherapy can be a reasonable and effective treatment option for dMMR/MSI-H locally advanced PCRC. Our report provides some support and evidence for neoadjuvant immunotherapy for locally advanced PCRC, while highlighting the importance of preoperative detection of microsatellite status for locally advanced PCRC.
Objective: To explore the relationship between the circular clock gene NPAS2 (neural PAS domain protein 2) and the survival prognosis of gastric cancer (GC) patients and clarify its role in evaluating GC prognosis. Methods: The tumor tissues and clinical data of 101 patients with GC were collected retrospectively. Immunohistochemical staining (IHC) was used to detect the expression of NPAS2 protein in GC and adjacent tissues. Univariate and multivariate Cox regression analysis was used to determine the independent prognostic factors of GC, and a nomogram prediction model was established. The ROC curve, the ROC area under the curve (AUC), the calibration curve, and C-index were used to evaluate the predictive effectiveness of the model. Kaplan Meier analysiswas used to compare the risk stratification of subgroups according to the median score in the nomogram model of each patient. Results: Microarray IHC analysis showed that the positive rate of NPAS2 protein expression in GC tissues was 65.35%, which was significantly higher than 30.69% in adjacent tissues. The high expression of NPAS2 was correlated with TNM stage (P<0.05), pN stage (P<0.05), metastasis (P<0.05), venous invasion (P<0.05), lymphatic invasion (P<0.05), and lymph node positive (P<0.05) of GC. Kaplan Meier survival analysis showed that the 3-year overall survival (OS) of patients with high NPAS2 expression was significantly shortened (P<0.0001). Univariate and multivariate COX regression analysis showed that TNM stage (P=0.009), metastasis (P=0.009), and NPAS2 expression (P=0.020) were independent prognostic factors of OS in GC patients for 3 years. The nomogram prediction model based on independent prognostic factors has a C-Index of 0.740 (95% CI: 0.713-0.767). Furthermore, subgroup analysis showed that the 3-year OS time of the high-risk group was significantly lower than that of the low-risk group (P<0.0001). Conclusion: NPAS2 is highly expressed in GC tissues and is closely related to worse OS in patients. Therefore, the evaluation of NPAS2 expression may be a potential marker for GC prognosis evaluation. Notably, the nomogram model based on NPAS2 can improve the accuracy of GC prognosis prediction and assist clinicians in postoperative patient management and decision-making.
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