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Journal of Chinese Integrative Medicine ›› 2012, Vol. 10 ›› Issue (4): 406-415.doi: 10.3736/jcim20120409

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Characteristic genomics of peripheral blood mononuclear cells of hepatocellular carcinoma patients with liver-kidney yin deficiency syndrome

Li Weng, Juan Du, Wen-ting He, Chang-quan Ling()   

  1. Department of Traditional Chinese Medicine, Changhai Hospital, Second Military Medical University, Shanghai 200433, China
  • Received:2011-10-25 Accepted:2011-12-23 Online:2012-04-20 Published:2018-04-15

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Objective: To explore the characteristic genomics of syndrome of liver-kidney yin deficiency in peripheral blood mononuclear cells of hepatocellular carcinoma (HCC) patients.
Methods: HCC patients with or without syndrome of liver-kidney yin deficiency were enrolled into the experimental group and the control group, respectively; their gene expression profiles were evaluated by a whole-genome Affymetrix GeneChip Human Genome U133 Plus 2.0 Array. The differentially expressed mRNAs were then selected by Gene Ontology (GO) and pathway analyses, respectively. Based on the results of GO and pathway analyses, gene coexpression networks were built according to the normalized signal intensity of specifically expressed genes. Finally, the results from microarray were confirmed by real-time fluorescence quantitative polymerase chain reaction and Western blot methods.
Results: The results showed that a set of 615 mRNAs were differentially expressed in the HCC patients with syndrome of liver-kidney yin deficiency. By GO enrichment analysis, the genes for anti-apoptosis, regulation of cell cycle, transmembrane transport, etc. were up-regulated or down-regulated in the experimental group. Another functional analysis of mRNAs by KEGG revealed that 10 signal transduction pathways were up-regulated and 16 were down-regulated, such as antigen processing and presentation, cell cycle, and protein export. Based on the above results, we constructed coexpression networks to determine which genes may play pivotal role in HCC patients with syndrome of liver-kidney yin deficiency. Some critical genes, including SEC62 (SEC62 homolog (S. cerevisiae)), CCNB1 (cyclin B1) and BIRC3 (baculoviral IAP repeat-containing 3), which rank the top 3 in |Δ normalized degree| were chosen. Of another 60 samples, we found that the mRNA expressions of SEC62, CCNB1 and BIRC3were significantly lower in HCC patients with syndrome of liver-kidney yin deficiency than those without syndrome of liver-kidney yin deficiency (P<0.01). Also, the protein expressions of SEC62, CCNB1 and BIRC3 were significantly lower (P<0.01).
Conclusion: Gene chip technique allows rapid and high-throughput screening for different gene expression in HCC patients with or without liver-kidney yin deficiency syndrome. The results of this study further confirm the hypothesis on the essence of syndrome, namely, a kind of deviation from the normal state in multigene style on the levels of both mRNA and protein.

Key words: liver neoplasms, liver-kidney yin deficiency, gene expression, genomics

Table 1

Primer sequences and length of products"

Gene Upstream Downstream Length (bp)
SEC62 5′-AGCTGACCCGAATGGAC-3′ 5′-AGAGCCGAGAATAGGCACCC-3′ 121
CCNB1 5′-GAAGATCAACATGGCAGGCG-3′ 5′-GCATTTTGGCCTGCAGTTGT-3′ 131
BIRC3 5′-CCATTGACTTTTCTGTCGCCA-3′ 5′-GCATTATCCTTCGGTTCCCAA-3′ 125
GAPDH 5′-TGTTGCCATCAATGACCCCTT-3′ 5′-CTCCACGACGTACTCAGCG-3′ 201

Table 2

Clinicopathologic charateristics in HCC patients with or without liver-kidney yin deficiency syndrome(x±s)"

Group n Tumor size (cm) AFP level (μg/L) Age (years) γ-GT (U/L) ALT (U/L)
Liver-kidney yin
deficiency syndrome		 3 3.77±0.14 165.67±95.99 57.33±1.20 165.67±95.99 47.33±14.77
Non-liver-kidney yin
deficiency syndrome		 3 3.83±0.28 169.67±112.62 57.00±1.15 169.97±112.62 53.67±23.82

Figure 1

GO-MAP based on biological process for differentially expressed genes Red: significant GO category for down-regulated genes; Blue: significant GO category for up-regulated genes; Yellow: significant GO category for both up-regulated and down-regulated genes. GO: Gene Ontology."

Figure 2

KEGG pathway analysis for differentially expressed genes Blue: significant pathway for down-regulated genes; Red: significant pathway for up-regulated genes"

Figure 3

Interaction network analysis of differentially expressed genes Red: up-regulated genes; Blue: down-regulated genes"

Table 3

Genes with |Δ normalized degree|>0.3 in the interaction network analysis"

Gene Description ΔNormalized degree (D-C)
SEC62 SEC62 homolog
(S. cerevisiae)		 –0.666 666 667
CCNB1 Cyclin B1 –0.372 549 020
BIRC3 Baculoviral IAP
repeat-containing 3		 –0.341 176 471

Figure 4

The mRNA expressions of Sec62, Cyclin B1 and Birc3 in HCC patients with or without kidney-liver yin deficiency syndrome A: HCC patients without liver-kidney yin deficiency syndrome; B: HCC patients with liver-kidney yin deficiency syndrome. The Sec62/cyclin B1/Birc3 mRNA levels were expressed in comparsion with the expression level of GAPDH mRNA. Data were analyzed by Mann-Whitney U test, n=3; **P<0.01, vs group A. HCC: hepatocellular carcinoma; GAPDH: glyceraldehyde-3-phosphate dehydrogenase."

Figure 5

The protein expressions of Sec62, Cyclin B1 and Birc3 in HCC patients with or without kidney-liver yin deficiency syndrome A: HCC patients without liver-kidney yin deficiency syndrome; B: HCC patients with liver-kidney yin deficiency syndrome. The signal intensities were corrected with that of β-actin as an internal control. Data were analyzed by Mann-Whitney U test, n=3; **P<0.01, vs group A. HCC: hepatocellular carcinoma."

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