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Kohla et al.                                                                                                                                                                         Transforming growth factor β1 in HCC

           Table 2: Tumor characteristics in HCC patients     Table 5: Serum levels of TGF-b1 and tumor burden
                                                              (vascular invasion, tumor size and number)
            Variable                       Number Percent (%)
            Site of nodule(s)                                  Tumor burden        TGF      Statistical   P-value
              Bi-lobar                       54       45                        (mean ± SD)    test
              Uni-lobar                      66       55       Vascular invasion              Mann     0.001
                Right lobe                   48       40         Yes          1909.29 ±1872.17  Whitney
                                                                 No
                                                                              1019.65 ±1425.38
                                                                                               test
                Left lobe                    18       15                                       3.32
            Number of nodules                                  Tumor size                     Kruskal   0.02
              Single                         58      48.3        < 5 cm       1106.06 ± 1541.75  Wallis Test
              Multiple                       62      51.6        5-8 cm       1217.14 ± 1522.95  7.2
                2                            18       15         > 8          1925.32 ± 1815.78
                                                                                              Mann
                3                            6        5        Tumor Number   1427.55 ± 1669.07  Whitney   0.964
                                                                 Single
                > 3                          38      31.6        Multiple     1495.79 ± 1717.45  test
            Size of nodule(s)                                                                 0.002
              Largest diameter for single       < 5 cm  47  39.1
              or sum of largest diameter     5-8 cm  18  15   TGF-b1: transforming growth factor beta 1
              (2-3 nodules)        > 8 cm    17      14.1
              Size of largest (> 3 nodules)  5-8 cm  6  5     Table 6: Number of cases
                                   > 8 cm    32      26.6                    Total   No. of      Censored
                                                               TGF          number  events    n      Percent
           HCC: hepatocellular carcinoma
                                                               Negative < 301  73     20      53      72.6%
                                                               Positive ≥ 301  107    42      65      60.7%
           Table 3: Serum levels of TGF-b1 in all subjects     Overall        180     62     118      65.6%
                         The studied groups
                            (mean ± SD)       Kruskal         TGF: transforming growth factor
           Variables   HCC     Cirrhotic   Control   Wallis   P-value
                     (n = 120)  (n = 30)  (n = 30)  test      Analysis of the ROC curve of alpha-fetoprotein (AFP)
                     1,687.47 ±   487.98 ±   250.16 ±
           TGF                                 33.990  0.000  showed that, at cut off value 20 µg/L area of AFP;
                     1,462.81   344.23  284.61
                                                              area under the curve for the prediction of HCC was
           HCC: hepatocellular carcinoma; TGF-b1: transforming growth   0.86 with 95%CI 0.815-0.930 at this cut-off; the
           factor beta 1
                                                              sensitivity was 72%, while the specificity was 43%.
           Table 4: Serum levels of TGF-b1 according to BCLC and
           Child-Pugh score                                   Combining  both  TGF-β1  (at  a  cut-off  value  of
                                                              301.9 pg/mL) and AFP (at a cut-off value of 20 µg/L)
                                            Kruskal
            Variable       TGF (mean ± SD)  Wallis test  P value  would raise the sensitivity to 90%, but decreasing the
            BCLC stage                                        specificity to 32%.
              A             652.83 ± 1084.60
              B             1378.95 ± 1660.50  12.100  0.007
              C             2150.68 ± 1970.01                 DISCUSSION
              D             1668.78 ± 1628.15
            Child classification
              A            1079.45 ± 1491.016                 TGF-β1 acts as a growth inhibitor in normal cells,
              B            1232.30 ± 1717.276  6.729  0.035   whereas in tumor cells, it loses the ability to mediate
              C             1668.78 ± 1628.15                 growth inhibition and instead promotes tumor
                                                              progression by enhancing migration, invasion, and
           BCLC: Barcelona clinic liver cancer; TGF-b1: transforming growth      [11]
           factor beta 1                                      survival of tumor cells  .
           with levels < 301.9 pg/mL was not reached with a   In liver diseases, the persistence of chronic
           probability of survival of 71.9%, the median survival   inflammation, as observed in chronic viral hepatitis,
           for patients with level ≥ 301.9 pg/mL was only 13   plays a major role in determining the shift in the
           months, the difference was statistically significant   TGF-β1 signaling pathway from tumor suppression to
           using log rank test (P = 0.04), as shown in Tables 6   increasing the risk of HCC [12] .
           and 7 and Figure 5.
                                                              Our study evaluated the serum levels of TGF-β1 in
           Analysis of the receiver operating characteristic   HCC patients, cirrhotic patient and normal subjects.
           (ROC) curve of TGF-β1 showed that, at cut-off value   Its aim was to determine the specific contribution of
           301.9 pg/mL of TGF-β1; area under the curve for the   TGF-β1 over-expression to progression of HCC.
           prediction of HCC was 0.765 and 95%CI 0.694-0.885,
           with a sensitivity of 72% and a specificity of 65%.  In  our  study,  we  demonstrated  significantly

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