Long-term DEHP/MEHP exposure promotes colorectal cancer stemness associated with glycosylation alterations.

Plasticizers are considered as environmental pollution released from medical devices and increased potential oncogenic risks in clinical therapy. Our previous studies have shown that long-term exposure to di-ethylhexyl phthalate (DEHP)/mono-ethylhexyl phthalate (MEHP) promotes chemotherapeutic drug resistance in colorectal cancer. In this study, we investigated the alteration of glycosylation in colorectal cancer following long-term plasticizers exposure. First, we determined the profiles of cell surface N-glycomes by using mass spectrometry and found out the alterations of α2,8-linkages glycans. Next, we analyzed the correlation between serum DEHP/MEHP levels and ST8SIA6 expression from matched tissues in total 110 colorectal cancer patients. Moreover, clinical specimens and TCGA database were used to analyze the expression of ST8SIA6 in advanced stage of cancer. Finally, we showed that ST8SIA6 regulated stemness in vitro and in vivo. Our results revealed long-term DEHP/MEHP exposure significantly caused cancer patients with poorer survival outcome and attenuated the expression of ST8SIA6 in cancer cells and tissue samples. As expected, silencing of ST8SIA6 promoted cancer stemness and tumorigenicity by upregulating stemness-associated proteins. In addition, the cell viability assay showed enhanced drug resistance in ST8SIA6 silencing cells treated with irinotecan. Besides, ST8SIA6 was downregulated in the advanced stage and positively correlated with tumor recurrence in colorectal cancer. Our results imply that ST8SIA6 potentially plays an important role in oncogenic effects with long-term phthalates exposure.

Bioinformatics Analyses Identify the Therapeutic Potential of ST8SIA6 for Colon Cancer.

Sialylation of glycoproteins is modified by distinct sialyltransferases such as ST3Gal, ST6Gal, ST6GalNAc, or ST8SIA with α2,3-, α2,6-, or α2,8-linkages. Alteration of these sialyltransferases causing aberrant sialylation is associated with the progression of colon cancer. However, among the ST8- sialyltransferases, the role of ST8SIA6 in colon cancer remains poorly understood. In this study, we explored the involvement of ST8SIA6 in colon cancer using multiple gene databases. The relationship between ST8SIA6 expression and tumor stages/grades was investigated by UALCAN analysis, and Kaplan-Meier Plotter analysis was used to analyze the expression of ST8SIA6 on the survival outcome of colon cancer patients. Moreover, the biological functions of ST8SIA6 in colon cancer were explored using LinkedOmics and cancer cell metabolism gene DB. Finally, TIMER and TISMO analyses were used to delineate ST8SIA6 levels in tumor immunity and immunotherapy responses, respectively. ST8SIA6 downregulation was associated with an advanced stage and poorly differentiated grade; however, ST8SIA6 expression did not affect the survival outcomes in patients with colon cancer. Gene ontology analysis suggested that ST8SIA6 participates in cell surface adhesion, angiogenesis, and membrane vesicle trafficking. In addition, ST8SIA6 levels affected immunocyte infiltration and immunotherapy responses in colon cancer. Collectively, these results suggest that ST8SIA6 may serve as a novel therapeutic target towards personalized medicine for colon cancer.

How far can the radiation dose be lowered in head CT with iterative reconstruction? Analysis of imaging quality and diagnostic accuracy.

OBJECTIVE: To evaluate the imaging quality of head CT at lowered radiation dose by combining filtered back projection (FBP) and iterative reconstruction (IR) algorithms. METHODS: Experimental group A (n = 66) underwent CT with 43 % tube current reduction, and group B (n = 58) received an equivalent reduced dose by lowering the tube voltage. An age- and sex-matched control group (n = 72) receiving the conventional radiation dose was retrospectively collected. Imaging for the control group was reconstructed by FBP only, while images for groups A and B were reconstructed by FBP and IR. The signal-to-noise ratios (SNRs), contrast-to-noise ratios (CNRs), sharpness, number of infarcts and severity of subcortical arteriosclerotic encephalopathy (SAE) were compared to assess imaging quality and diagnostic accuracy. RESULTS: There were no significant differences in SNRs and CNRs between group A and the control group. There were significantly decreased SNRs and increased CNRs in group B. Image sharpness decreased in both groups. Correlations between detected infarcts and severity of SAE across FBP and IR were high (r = 0.73-0.93). Head diameter was the only significant factor inversely correlated with infratentorial imaging quality. CONCLUSION: Head CT with 43 % reduced tube current reconstructed by IR provides diagnostic imaging quality for outpatient management. KEY POINTS: • Cranial CT using iterative reconstruction provides diagnostic images with 43 % mAs reduction. • Blurring of infratentorial images becomes evident using low-radiation head CT. • Head diameter was inversely correlated with imaging quality in the infratentorium. • Lowering tube kilovoltage requires a higher radiation dose to maintain image quality.