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Investigating the pretreatment miRNA expression patterns of advanced hepatocellular carcinoma patients in association with response to TACE treatment.

El-Halawany MS, Ismail HM, Zeeneldin AA, Elfiky A, Tantawy M, Kobaisi MH, Hamed I, Abdel Wahab AH - Biomed Res Int (2015)

Bottom Line: Out of 94 examined miRNAs, 53 were significantly upregulated while 3 miRNAs were downregulated in HCC samples compared to normal liver samples.Furthermore, we observed that a panel of 10 miRNAs was significantly associated with patients' survival status at 1 year.These results highlight the potential implications of pretreatment miRNAs expression profiling in prediction of the patients' response to TACE treatment in liver cancer.

View Article: PubMed Central - PubMed

Affiliation: Zoology Department, Faculty of Science, Cairo University, El-Gamaa Street, Giza 12613, Egypt.

ABSTRACT
Hepatocellular carcinoma (HCC) is a lethal malignancy with poor prognosis and limited treatment options. Transarterial chemoembolization (TACE) using chemotherapy agents-doxorubicin and cisplatin-is an accepted treatment option for locally advanced hepatocellular carcinoma. In the current study, we analyzed the expression pattern of a selected panel of 94 miRNAs in archival samples that were collected prior to treatment from 15 Egyptian patients diagnosed with advanced hepatocelleular carcinoma. We observed an overall increase in miRNA expression in HCC samples compared with normal subjects. Out of 94 examined miRNAs, 53 were significantly upregulated while 3 miRNAs were downregulated in HCC samples compared to normal liver samples. Comparing the pretreatment miRNA expression profiles in HCC patients and the patients response to TACE treatment resulted in the identification of a set of 12 miRNAs that are significantly upregulated in nonresponders group. This miRNA panel includes miR-10a-1, miR-23a-1, miR-24, miR-26a, miR-27a, miR-30c, miR-30e, miR-106b, miR-133b, miR-199a, miR-199-3p, and miR-200b. Furthermore, we observed that a panel of 10 miRNAs was significantly associated with patients' survival status at 1 year. These results highlight the potential implications of pretreatment miRNAs expression profiling in prediction of the patients' response to TACE treatment in liver cancer.

No MeSH data available.


Related in: MedlinePlus

miRNA expression profile associated with patients' survival status at 1 year. Expression of miRNAs was determined by real-time PCR in HCC patients. Expression profiles were normalized against normal controls. Log2 fold of change of miRNA was compared in HCC patients at one year of survival. (a) Graph shows 10 miRNAs that were significantly deregulated in association with survival status of patients at one year. (b) Heatmap of expression profile of 10 miRNAs in (a). (c) Hierarchical clustering with the 10 altered miRNAs showed a clear separation between alive and dead groups.
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fig4: miRNA expression profile associated with patients' survival status at 1 year. Expression of miRNAs was determined by real-time PCR in HCC patients. Expression profiles were normalized against normal controls. Log2 fold of change of miRNA was compared in HCC patients at one year of survival. (a) Graph shows 10 miRNAs that were significantly deregulated in association with survival status of patients at one year. (b) Heatmap of expression profile of 10 miRNAs in (a). (c) Hierarchical clustering with the 10 altered miRNAs showed a clear separation between alive and dead groups.

Mentions: miRNA expressions in HCC cancer samples were compared with patients' clinicopathological parameters including tumour stage and patient's age at diagnosis and survival. Results were tested for statistical significance difference using Chi-square and Mann-Whitney test. No significant association was observed between miRNA expression and patients' age or tumour stage (data not shown). To assess if there is an association between the pretreatment miRNA expression and the patients' survival status, we compared the expression profile of miRNAs and patients' overall survival at one year. A significant association was observed between the patients' survival status at one year and the regulation of 10 miRNAs. This panel included 9 significantly upregulated miRNAs in alive subjects (miR-21-2, miR-3-1-1, miR-98-1, miR-107-1, miR-181a-2, miR-210-1, miR-491-1, and miR-664-1) while one miRNA was significantly downregulated (miR-602-2) (Figure 4(a) and heatmap in Figure 4(b)). Hierarchical clustering using the significantly altered set of 10 miRNAs showed a clear separation between alive and dead subjects (Figure 4(c)).


Investigating the pretreatment miRNA expression patterns of advanced hepatocellular carcinoma patients in association with response to TACE treatment.

El-Halawany MS, Ismail HM, Zeeneldin AA, Elfiky A, Tantawy M, Kobaisi MH, Hamed I, Abdel Wahab AH - Biomed Res Int (2015)

miRNA expression profile associated with patients' survival status at 1 year. Expression of miRNAs was determined by real-time PCR in HCC patients. Expression profiles were normalized against normal controls. Log2 fold of change of miRNA was compared in HCC patients at one year of survival. (a) Graph shows 10 miRNAs that were significantly deregulated in association with survival status of patients at one year. (b) Heatmap of expression profile of 10 miRNAs in (a). (c) Hierarchical clustering with the 10 altered miRNAs showed a clear separation between alive and dead groups.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4355598&req=5

fig4: miRNA expression profile associated with patients' survival status at 1 year. Expression of miRNAs was determined by real-time PCR in HCC patients. Expression profiles were normalized against normal controls. Log2 fold of change of miRNA was compared in HCC patients at one year of survival. (a) Graph shows 10 miRNAs that were significantly deregulated in association with survival status of patients at one year. (b) Heatmap of expression profile of 10 miRNAs in (a). (c) Hierarchical clustering with the 10 altered miRNAs showed a clear separation between alive and dead groups.
Mentions: miRNA expressions in HCC cancer samples were compared with patients' clinicopathological parameters including tumour stage and patient's age at diagnosis and survival. Results were tested for statistical significance difference using Chi-square and Mann-Whitney test. No significant association was observed between miRNA expression and patients' age or tumour stage (data not shown). To assess if there is an association between the pretreatment miRNA expression and the patients' survival status, we compared the expression profile of miRNAs and patients' overall survival at one year. A significant association was observed between the patients' survival status at one year and the regulation of 10 miRNAs. This panel included 9 significantly upregulated miRNAs in alive subjects (miR-21-2, miR-3-1-1, miR-98-1, miR-107-1, miR-181a-2, miR-210-1, miR-491-1, and miR-664-1) while one miRNA was significantly downregulated (miR-602-2) (Figure 4(a) and heatmap in Figure 4(b)). Hierarchical clustering using the significantly altered set of 10 miRNAs showed a clear separation between alive and dead subjects (Figure 4(c)).

Bottom Line: Out of 94 examined miRNAs, 53 were significantly upregulated while 3 miRNAs were downregulated in HCC samples compared to normal liver samples.Furthermore, we observed that a panel of 10 miRNAs was significantly associated with patients' survival status at 1 year.These results highlight the potential implications of pretreatment miRNAs expression profiling in prediction of the patients' response to TACE treatment in liver cancer.

View Article: PubMed Central - PubMed

Affiliation: Zoology Department, Faculty of Science, Cairo University, El-Gamaa Street, Giza 12613, Egypt.

ABSTRACT
Hepatocellular carcinoma (HCC) is a lethal malignancy with poor prognosis and limited treatment options. Transarterial chemoembolization (TACE) using chemotherapy agents-doxorubicin and cisplatin-is an accepted treatment option for locally advanced hepatocellular carcinoma. In the current study, we analyzed the expression pattern of a selected panel of 94 miRNAs in archival samples that were collected prior to treatment from 15 Egyptian patients diagnosed with advanced hepatocelleular carcinoma. We observed an overall increase in miRNA expression in HCC samples compared with normal subjects. Out of 94 examined miRNAs, 53 were significantly upregulated while 3 miRNAs were downregulated in HCC samples compared to normal liver samples. Comparing the pretreatment miRNA expression profiles in HCC patients and the patients response to TACE treatment resulted in the identification of a set of 12 miRNAs that are significantly upregulated in nonresponders group. This miRNA panel includes miR-10a-1, miR-23a-1, miR-24, miR-26a, miR-27a, miR-30c, miR-30e, miR-106b, miR-133b, miR-199a, miR-199-3p, and miR-200b. Furthermore, we observed that a panel of 10 miRNAs was significantly associated with patients' survival status at 1 year. These results highlight the potential implications of pretreatment miRNAs expression profiling in prediction of the patients' response to TACE treatment in liver cancer.

No MeSH data available.


Related in: MedlinePlus