Immune-related gene expression signatures in colorectal cancer.

The immune system is crucial in regulating colorectal cancer (CRC) tumorigenesis. Identification of immune-related transcriptomic signatures derived from the peripheral blood of patients with CRC would provide insights into CRC pathogenesis, and suggest novel clues to potential immunotherapy strategies for the disease. The present study collected blood samples from 59 patients with CRC and 62 healthy control patients and performed whole blood gene expression profiling using microarray hybridization. Immune-related gene expression signatures for CRC were identified from immune gene datasets, and an algorithmic predictive model was constructed for distinguishing CRC from controls. Model performance was characterized using an area under the receiver operating characteristic curve (ROC AUC). Functional categories for CRC-specific gene expression signatures were determined using gene set enrichment analyses. A Kaplan-Meier plotter survival analysis was also performed for CRC-specific immune genes in order to characterize the association between gene expression and CRC prognosis. The present study identified five CRC-specific immune genes [protein phosphatase 3 regulatory subunit Bα (PPP3R1), amyloid ß precursor protein, cathepsin H, proteasome activator subunit 4 and DEAD-Box Helicase 3 X-Linked]. A predictive model based on this five-gene panel showed good discriminatory power (independent test set sensitivity, 83.3%; specificity, 94.7%, accuracy, 89.2%; ROC AUC, 0.96). The candidate genes were involved in pathways associated with 'adaptive immune responses', 'innate immune responses' and 'cytokine signaling'. The survival analysis found that a high level of PPP3R1 expression was associated with a poor CRC prognosis. The present study identified five CRC-specific immune genes that were potential diagnostic biomarkers for CRC. The biological function analysis indicated a close association between CRC pathogenesis and the immune system, and may reveal more information about the immunogenic and pathogenic mechanisms driving CRC in the future. Overall, the association between PPP3R1 expression and survival of patients with CRC revealed potential new targets for CRC immunotherapy.

Interleukin (IL)-13, Prostaglandin E2 (PGE2), and Prostacyclin 2 (PGI2) Activate Hepatic Stellate Cells via Protein kinase C (PKC) Pathway in Hepatic Fibrosis.

BACKGROUND Protein kinase C (PKC), interleukin (IL)-13, prostaglandin E2 (PGE2), and prostacyclin 2 (PGI2) can all play crucial roles in pulmonary fibrosis. However, their functions remain unclear in hepatic fibrosis mediated by hepatic stellate cells (HSCs), which has been demonstrated to be related to transforming growth factor-ß (TGF-ß) and platelet-derived growth factor (PDGF). MATERIAL AND METHODS All the experiments were based on LX-2 Hepatic stellate cells. The expression of TGF-ß1 and PDGF were assessed by ELISA, RT-PCR, and Western blotting in human HSCs treated by IL-13, PGE2, and PGI2, respectively. At the same time, bridge assay and CCK8 assay were used to detect the cell proliferation and activity, PKC activity assay was used to test the activity of PKC, and PKC agonist and antagonist were used to verify the results obtained previously. RESULTS We found that IL-13, PGE2, and PGI2 significantly enhanced the expression of TGF-ß1 and PDGF in human HSCs, which also clearly improved the proliferation and cell activity of HSCs. Moreover, PKC activity was significantly increased following IL-13, PGE2, and PGI2 treatments. We also found that the expression of TGF-ß1 and PDGF, as well as the proliferation and cell activity of HSCs, were significantly enhanced by the PKC agonist phorbol 12-myristate 13-acetate (PMA), but suppressed by the PKC antagonist calphostin C. CONCLUSIONS We found that IL-13, PGE2, and PGI2 stimulated HSCs proliferation and secretion of TGF-ß1 and PDGF by activating PKC, which predicted their potential roles in hepatic fibrosis.

Study of the correlation between H-ras mutation and primary hepatocellular carcinoma.

The aim of this study was to investigate the correlation between H-ras mutation and primary hepatocellular carcinoma (HCC) and to describe the role of H-ras mutation in carcinogenesis. Clinical samples of 69 patients were collected and the expression levels of H-ras in HCC and the surrounding normal tissues were examined using HotStarTaq PCR. H-ras mutation was further analyzed using the PCR direct sequencing method. The results showed that H-ras mutation was present in 49 samples (49/69, 71.01%), of which 19 had codon 40 mutated from CTA to CTG and 30 had codon 61 mutated from GGC to AGC. By contrast, only 2 mutations were found in the normal tumor-adjacent tissues. The H-ras mutation rate in the high-risk of metastatic recurrence group was markedly higher than that in the low-risk group (P<0.01). The H-ras mutation rate in patients with metastatic recurrence during postoperative follow-up was also significantly higher than that in patients without metastatic recurrence (P<0.01). Based on the above results, the H-ras mutation frequency in cancer tissues is markedly higher compared with that in normal tissues. H-ras mutation may play an important role in the genesis and development of HCC and may serve as a reliable marker for individual comprehensive therapy in HCC.

Expression of farnesyltransferase in primary liver cancer.

BACKGROUND: Primary liver cancer (PLC) is a common malignant tumor. Over the past decade, although farnesyltransferase (FTase) has emerged as a significant target for anticancer therapies and has become a hotspot of cancer research, its exact mechanism of action remains unknown. The aim of this study was to investigate the expression of FTase in PLC and its role in the development of PLC. METHODS: Expression of FTase was detected by real-time fluorescent quantitative-polymerase chain reaction (FQ-PCR) in cancer and surrounding normal tissues from 32 patients with PLC. RESULTS: Expression of FTase mRNA in PLC was significantly higher than that in normal hepatic tissues (P < 0.001). Overexpression of FTase was as high as 87.5%. The positive rate for FTase mRNA in the high tendency to metastatic recurrence group was obviously higher than that in the low tendency to metastatic recurrence group (P = 0.02). The positive rate for FTase mRNA in patients with metastatic recurrence during postoperative follow-up was also significantly higher than that in those without metastatic recurrence (P = 0.01). CONCLUSIONS: The level of FTase mRNA expression in cancer tissues is much higher than in normal tissues. FTase may play an important role in the genesis and development of PLC and may be one of the reliable markers for the metastatic activity gained by liver tumor cells. FTase could be used clinically in predicting metastatic recurrence of PLC.

[Value of modified APACHE II score in predicting postoperative complications in patients with acute obstructing colorectal carcinoma].

OBJECTIVE: To evaluate the value of modified acute physiologic and chronic health score (APACHE II score) in predicting postoperative complications in patients with acute obstructing colorectal carcinoma. METHODS: Postoperative complications in 92 patients with acute obstructing colorectal carcinoma were evaluated by APACHE II score and modified APACHE II score (severe organ dysfunction and immune damage in chronic health indicators were replaced by the duration and degree of obstruction, which were considered as the severity of intestinal obstruction). The sensitivity, specificity, and Youden index were compared with regard to complication prediction. Receiver operating characteristic curves were plotted to calculate area under the curve(AUC). RESULTS: Twenty-five patients developed postoperative complications including 3 deaths. The APACHE-II score(13.72±4.24), modified APACHE II score (19.28±4.92), intestinal obstruction severity score (5.56±2.20) were significantly higher in patients with complications than those in patients without complications (10.58±3.44, 14.69±3.73, 4.10±1.52, all P<0.01). The sensitivity, specificity, accuracy, Youden index, and AUC were 0.640, 0.940, 0.859, 0.580, and 0.839 for the modified APACHE-II score with 20 being the optimal cut-off point, respectively, and were 0.560, 0.896, 0.804, 0.456, and 0.784 for APACHE-II (14 was the optimal cut-off point), respectively. CONCLUSION: The modified APACHE-II score system with the intestinal obstruction severity score is a better prediction method for the occurrence of postoperative complications in patients with acute obstructing colorectal carcinoma.