Purpose Pancreatic cancer is associated with a high mortality rate owing to insufficient approaches for early diagnosis and the invasive biological behavior of the cancer. CD26 is a membrane-anchored protein involved in multiple physiological and pathological processes. Here, we investigated correlations between CD26 expression and clinicopathological features in patients with pancreatic tumors. Methods We collected 170 tumor tissue specimens and 138 paired paratumoral tissues from patients with pancreatic tumors and evaluated CD26 expression using immunohistochemistry. Results CD26 was expressed in 79.4% of pancreatic tumors, which was significantly ( P < 0.001) higher than that in paratumoral pancreatic tissues (23.2%). High expression of CD26 was correlated with ABO blood type ( P = 0.035), malignancy degree ( P = 0.001), CA199 ( P = 0.01), and CA242 ( P = 0.027). In pancreatic malignancies, CD26 expression was observed in 80.7% (130/161) of cases. Lower CD26 expression was correlated with longer disease-free survival ( P = 0.048) and overall survival ( P = 0.024) and was an independent predictor of overall survival (hazard ratio [HR]: 1.713; P = 0.042). Similar results were observed in pancreatic ductal adenocarcinoma (PDAC) tissues, and CD26 expression level (HR: 2.117; P = 0.008) was an independent predictor of overall survival in patients with PDAC. CD26 expression was significantly increased in pancreatic tumors and gradually increased with increasing malignancy degree, suggesting that CD26 may be involved in the tumorigenic proliferation of pancreatic tumors. Conclusion Therefore, CD26 is a potential marker for early diagnosis and a promising therapeutic target in pancreatic tumors.
Background. Alternative splicing (AS) plays a crucial role in regulating the progression of colorectal cancer (CRC), but its distribution remains to be explored. Here, we aim to investigate the genes edited by AS which show differential expression in patients with mismatch repair deficiency (dMMR)/microsatellite instability (MSI). Materials and Methods. We applied long-read nanopore sequencing to determine the mRNA profiles and screen AS genes using Oxford Nanopore Technologies (ONT) method in ten paired CRC tissues. CRC tissue and plasma samples were used to validate the differential genes with AS using real-time fluorescent quantitative PCR, immunohistochemistry, and enzyme-linked immunosorbent assay. Results. ONT sequencing identified 404 genes were downregulated, and 348 genes were upregulated in MSI cancer tissues compared with microsatellite stability (MSS) cancer tissues. In total, 6,200 AS events were identified in 2,728 mRNA transcripts. WGCNA revealed dMMR/MSI-correlated gene modules, including INHBA and RPL22L1, which were upregulated; conversely, HMGCS2 was downregulated in MSI cancer. Overexpression of RPL22L1, INHBA, and CAPZA1 was further confirmed in CRC tissues. INHBA was found to be associated with tumor lymphatic metastasis. Importantly, the levels of INHBA in CRC plasma were significantly increased compared with those in noncancer plasma. INHBA showed a higher level in dMMR/MSI CRC than in MSS CRC, indicating that INHBA is a useful biomarker. Conclusion. Our results showed that ONT-identified genes provide a pool to explore AS-associated markers for dMMR/MSI CRC. We demonstrated INHBA as a promising signature for clinical application in predicting tumor lymphatic metastasis and screening dMMR/MSI candidates.
PurposeExtralevator (ELAPE) and abdominoperineal excision (APE) are two major surgical approaches for low rectal cancer patients. Although excellent short-term efficacy is achieved in patients undergoing ELAPE, the long-term benefits have not been established. In this study we compared the survival outcomes in low rectal cancer patients who underwent ELAPE and APE.MethodsOne hundred fourteen patients were enrolled, including 68 in the ELAPE group and 46 in the APE group at the Beijing Chaoyang Hospital, Capital Medical University from January 2011 to December 2018. The baseline characteristics, overall survival (OS), progression-free survival (PFS), and local recurrence-free survival (LRFS) were calculated and compared between the two groups.ResultsDemographics and tumor stage were comparable between the two groups. The 5-year PFS (67.2 per cent versus 38.6 per cent, log-rank P = 0.008) and LRFS (87.0 per cent versus 62.3 per cent, log-rank P = 0.047) were significantly improved in the ELAPE group compared to the APE group, and the survival advantage was especially reflected in patients with pT3 tumors, positive lymph nodes or even those who have not received neoadjuvant chemoradiotherapy. Multivariate analysis showed that APE was an independent risk factor for OS (hazard ratio 3.000, 95 per cent c.i. 1.171 to 4.970, P = 0.004) and PFS (hazard ratio 2.730, 95 per cent c.i. 1.506 to 4.984, P = 0.001).Conclusion Compared with APE, ELAPE improved long-term outcomes for low rectal cancer patients, especially among patients with pT3 tumors, positive lymph nodes or those without neoadjuvant chemoradiotherapy.
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