Significance of differentially methylated genes in prostate cancer tissues, analyzed using Infinium Methylation27 BeadChips
| Gene | Sensitivity (95% CI) | (95% CI) | AUC | t Test (P) | Transcription start site | Strand | CpG island location |
|---|---|---|---|---|---|---|---|
| A, Genes that are significantly methylated in prostate cancer tissues (n = 158) compared with normal prostate (n = 34)a | |||||||
| A0X1 | 96.2 (91.9–98.5) | 100 (89.7–100) | 0.992 | <0.0001 | 41 | + | 2: 201,158,654–201,159,798 |
| CYBA | 95.5 (91.1–98.2) | 97.1 (84.7–99.9) | 0.988 | <0.0001 | 83 | − | 16: 87,244,422–87,245,165 |
| EDG3 | 93.0 (87.9–96.4) | 97.1 (84.7 to 99.9) | 0.97 | <0.0001 | 363 | + | 9: 90,794,956–90,796,827 |
| ELF4 | 88.6 (82.6–93.1) | 100 (89.7–100) | 0.994 | <0.0001 | 600 | − | X: 129,071,186–129,073,330 |
| EPB41L3 | 93.7 (88.7–96.9) | 100 (89.7–100) | 0.978 | <0.0001 | 185 | − | 18: 5,532,741–5,534,303 |
| FLJ12056 | 94.3 (89.5–97.4) | 100 (89.7–100) | 0.978 | <0.0001 | 316 | + | 2: 71,058,922–71,060,108 |
| FLJ90650 | 96.2 (91.9–98.6) | 100 (89.7–100) | 0.994 | <0.0001 | 449 | + | 5: 115,324,903–115,327,577 |
| FLT4 | 99.4 (96.5–99.9) | 100 (89.7–100) | 0.999 | <0.0001 | 691 | − | 5: 180,008,152–180,010,059 |
| GAS6 | 96.2 (91.9–98.6) | 100 (89.7–100) | 0.99 | <0.0001 | 964 | + | 13: 113,546,578–113,548,278 |
| GRASP | 96.2 (91.9–98.6) | 100 (89.7–100) | 0.993 | <0.0001 | 159 | + | 12: 50,686,496–50,688,060 |
| GSTP1 | 91.8 (86.3–95.6) | 100 (89.7–100) | 0.995 | <0.0001 | 755 | + | 11: 67,106,980–67,108,634 |
| HAAO | 93.0 (87.9–96.5) | 100 (89.7–100) | 0.979 | <0.0001 | 454 | − | 2: 42,873,041–42,874,496 |
| HIF3A | 95.6 (91.1–98.2) | 100 (89.7–100) | 0.989 | <0.0001 | 153 | + | 19: 51,491,754–51,492,473 |
| HOXC11 | 89.2 (83.3–93.6) | 97.1 (84.7–99.9) | 0.985 | <0.0001 | 20 | + | 12: 52,652,893–52,656,105 |
| LEP | 98.1 (94.6–99.6) | 97.1 (84.7–99.9) | 0.997 | <0.0001 | 51 | + | 7: 127,667,928–127,668,724 |
| MGC39606 | 95.6 (91.1–98.2) | 100 (89.7–100) | 0.992 | <0.0001 | 634 | + | X: 134,383,127–134,384,321 |
| MOBKL2B | 92.4 (87.1–96.0) | 100 (89.7–100) | 0.97 | <0.0001 | 851 | − | 9: 27,517,915–27,520,017 |
| RAB34 | 91.8 (86.3–95.6) | 94.1 (80.3–99.3) | 0.976 | <0.0001 | 157 | − | 17: 24,068,248–24,069,280 |
| RARβ | 93.0 (87.9–96.5) | 100 (89.7–100) | 0.986 | <0.0001 | 352 | + | 3: 25,444,208–25,445,101 |
| RHCG | 95.6 (91.1–98.2) | 100 (89.7–100) | 0.993 | <0.0001 | 110 | − | 15: 87,840,274–87,841,084 |
| RND2 | 93.0 (87.9–96.5) | 100 (89.7–100) | 0.996 | <0.0001 | 180 | + | 17: 38,429,704–38,431,262 |
| SLC34A2 | 91.1 (85.6–95.1) | 94.1 (80.3–99.3) | 0.966 | <0.0001 | 44 | + | 4: 25,266,077–25,266,795 |
| SPATA6 | 95.6 (91.1–98.2) | 100 (89.7–100) | 0.991 | <0.0001 | 595 | − | 1: 48,709,694–48,710,842 |
| TPM4 | 94.9 (90.3–97.8) | 100 (89.7–100) | 0.977 | <0.0001 | 306 | + | 19: 16,047,744–16,049,758 |
| ZNF154 | 97.5 (93.6–99.3) | 94.1 (80.3–99.3) | 0.99 | <0.0001 | 100 | − | 19: 62,911,404–62,912,681 |
| B, Hypermethylated genes in tissues of patients with recurrent prostate cancer (n = 98) compared with nonrecurrent cancer (n = 60)b | |||||||
| ACTL6B | 65.3 (55.1–74.6) | 66.7 (53.3–78.3) | 0.702 | <0.0001 | 136 | − | 7: 100,091,590–100,092,362 |
| AEBP1 | 63.3 (52.9–72.8) | 60.0 (46.5–72.4) | 0.646 | <0.0021 | 38 | + | 7: 44,110,152–44,111,361 |
| AMID | 77.5 (68.0–85.4) | 76.7 (64.0–86.6) | 0.843 | <0.0001 | 25 | − | 10: 71,562,005–71,562,897 |
| CD8A | 75.5 (65.8–83.6) | 71.7 (58.6–82.5) | 0.829 | <0.0001 | 114 | − | 2: 86,869,360–86,871,837 |
| CRIP1 | 61.2 (50.8–70.9) | 60.0 (46.5–72.4) | 0.638 | <0.0037 | 93 | + | 14: 105,023,580–105,025,363 |
| FLJ30934 | 80.6 (71.4–87.9) | 78.3 (65.8–87.9) | 0.862 | <0.0001 | 82 | + | 11: 65,357,151–65,358,255 |
| FLNC | 79.6 (70.3–87.1) | 81.7 (69.6–90.5) | 0.864 | <0.0001 | 131 | + | 7: 128,257,322–128,258,463 |
| FMOD | 76.5 (66.9–84.5) | 68.3 (55.0–79.7) | 0.748 | <0.0001 | 97 | − | 1: 201,586,895–201,587,112 |
| FOXE3 | 65.3 (55.0–74.6) | 63.3 (49.9–75.4) | 0.697 | <0.0001 | 570 | + | 1: 47,654,351–47,655,785 |
| GAS7 | 66.3 (56.1–75.6) | 66.7 (53.3–78.3) | 0.744 | <0.0001 | 395 | − | 17: 10,041,659–10,043,517 |
| GDPD5 | 70.4 (60.3–79.2) | 65.4 (51.6–76.8) | 0.713 | <0.0001 | 408 | − | 11: 74,913,525–74,915,608 |
| HS3ST2 | 65.3 (55.0–74.6) | 75.0 (62.1–85.3) | 0.798 | <0.0001 | 257 | + | 16: 22,732,005–22,734,135 |
| LOC349136 | 67.3 (57.1–76.5) | 65.0 (51.6–76.9) | 0.742 | <0.0001 | 479 | − | 7: 150,736,827–150,739,238 |
| NEUROG1 | 66.3 (56.1–75.6) | 70.0 (56.8–81.2) | 0.731 | <0.0001 | 19 | − | 5: 134,898,284–134,900,130 |
| PLTP | 68.4 (58.2–77.4) | 75.1 (62.1–85.3) | 0.709 | <0.0001 | 165 | − | 20: 43,972,342–43,974,350 |
| PTGER2 | 66.3 (56.1–75.6) | 66.7 (53.3–78.3) | 0.739 | <0.0001 | 199 | + | 14: 51,850,265–51,852,038 |
| RASGRF2 | 69.4 (59.3–78.3) | 71.7 (58.6–82.5) | 0.763 | <0.0001 | 106 | + | 5: 80,291,476–80,292,927 |
| RUNX3 | 67.4 (57.1–76.5) | 71.7 (58.6–82.6) | 0.746 | <0.0001 | 528 | − | 1: 25,127,692–25,131,906 |
| SIX6 | 65.3 (55.0–74.6) | 68.3 (55.0–79.7) | 0.745 | <0.0001 | 185 | + | 14: 60,045,112–60,046,647 |
| SLC9A3 | 69.4 (59.3–78.3) | 70.0 (56.8–81.2) | 0.713 | <0.0001 | 178 | − | 5: 576,269–577,990 |
| SPSB4 | 62.2 (51.9–71.8) | 61.7 (48.2–73.9) | 0.658 | <0.0008 | 91 | + | 3: 142,252,136–142,254,676 |
| SRD5A2 | 70.4 (60.3–79.2) | 71.7 (58.6–82.5) | 0.748 | <0.0001 | 125 | − | 2: 31,658,633–31,660,643 |
| SUSD3 | 64.3 (54.0–73.7) | 63.3 (49.9–75.4) | 0.652 | <0.0014 | 560 | + | 9: 94,860,370–94,861,840 |
| SYT10 | 66.3 (56.1–75.6) | 65.4 (51.6–76.8) | 0.714 | <0.0001 | 254 | − | 12: 33,482,438–33,484,467 |
| TMEM74 | 66.3 (56.1–75.6) | 68.3 (55.0–79.7) | 0.664 | <0.0005 | 14 | − | 8: 109,868,266–109,869,213 |
| C, Significance of genes methylated in prostate cancer tissues of patients with clinical recurrence (n = 59) compared with patients with only biochemical recurrence (n = 39)c | |||||||
| CHST7 | 69.5 (56.1–80.8) | 64.1 (47.2–78.8) | 0.668 | <0.0050 | 255 | + | X: 46,317,905–46,319,911 |
| LMX1B | 71.2 (57.9–82.2) | 64.1 (47.2–78.8) | 0.684 | <0.0021 | 106 | + | 9: 128,412,539–128,418,074 |
| PHLDA 3 | 61.0 (47.4–73.4) | 59.0 (42.1–74.4) | 0.606 | <0.0772 | 348 | − | 1: 199,704,096–199,705,294 |
| RAFTLIN | 62.7 (49.1–75.0) | 64.1 (47.2–78.8) | 0.668 | <0.0050 | 89 | − | 3: 16,529,156–16,530,542 |
| RASGRF2 | 66.1 (52.6–77.9) | 69.2 (52.4–82.9) | 0.690 | <0.0015 | 106 | + | 5: 80,291,476–80,292,927 |
| TNFRSF10D | 62.7 (49.2–74.9) | 66.6 (49.7–80.9) | 0.700 | <0.0008 | 25 | − | 8: 23,076,422–23,077,641 |
| ZNF135 | 59.3 (45.7–71.9) | 61.5 (44.6–76.6) | 0.664 | <0.0061 | 144 | + | 19: 63,262,091–63,264,376 |
| D, Genes that are methylated in tissues of patients with systemic recurrence (n = 23) compared with local recurrence (n = 36)d | |||||||
| ALPL | 65.2 (42.7–83.6) | 63.8 (46.2–79.1) | 0.683 | <0.0182 | 269 | + | 1: 21,707,968–21,709,033 |
| AMPH | 65.2 (42.7–83.6) | 75.0 (57.8–87.8) | 0.77 | <0.0005 | 35 | − | 7: 38,636,784–38,637,861 |
| BCDIN3 | 78.2 (56.3–92.5) | 83.3 (67.1–93.6) | 0.861 | <0.0001 | 873 | + | 7: 99,863,663–99,866,414 |
| BCL11B | 82.6 (61.2–95.0) | 80.5 (63.9–91.8) | 0.797 | <0.0001 | 274 | − | 14: 98,806,507–98,807,587 |
| BRD4 | 73.9 (51.6–89.7) | 69.4 (51.8–83.6) | 0.724 | <0.0038 | 665 | − | 19: 15,252,811–15,253,031 |
| C18orf34 | 78.2 (56.3–92.5) | 77.7 (60.8–89.8) | 0.806 | <0.0001 | 174 | − | 18: 29,274,320–29,275,128 |
| DCAMKL1 | 82.6 (61.2–95.5) | 91.6 (77.5–98.2) | 0.874 | <0.0001 | 734 | − | 13: 35,602,437–35,603,802 |
| FGF5 | 91.3 (71.9–98.9) | 83.3 (67.1–93.6) | 0.911 | <0.0001 | 544 | + | 4: 81,405,716–81,407,598 |
| FLJ42486 | 82.6 (61.2–95.0) | 77.7 (60.8–89.8) | 0.834 | <0.0001 | 99 | − | 14: 104,141,516–104,142,673 |
| JAM2 | 86.9 (66.4–97.2) | 86.1 (70.5–95.3) | 0.936 | <0.0001 | 587 | + | 21: 25,933,195–25,934,679 |
| LHX9 | 82.6 (61.2–95.0) | 69.4 (51.8–83.6) | 0.822 | <0.0001 | 106 | + | 1: 196,146,152–196,148,467 |
| LOC283537 | 78.2 (56.3–92.5) | 75.0 (57.8–87.8) | 0.811 | <0.0001 | 363 | − | 13: 28,190,499–28,191,650 |
| LRAT | 65.2 (42.7–83.6) | 72.2 (54.8–85.8) | 0.727 | <0.0034 | 462 | + | 4: 155,882,485–155,885,476 |
| PDE4B | 91.3 (71.9–98.9) | 77.7 (60.8–89.8) | 0.856 | <0.0001 | 423 | + | 1: 66,030,397–66,031,906 |
| POU3F3 | 91.3 (71.9–98.9) | 75.2 (57.8–87.8) | 0.865 | <0.0001 | 248 | + | 2: 104,835,039–104,840,521 |
| PTGS2 | 60.8 (38.5–80.2) | 80.5 (63.9–91.8) | 0.688 | <0.0153 | 37 | − | 1: 184,915,751–184,916,808 |
| RASGRF2 | 73.9 (51.6–89.7) | 75.4 (57.8–87.8) | 0.788 | <0.0002 | 106 | + | 5: 80,291,476–80,292,927 |
| SLC27A6 | 78.2 (56.3–92.5) | 69.4 (51.8–83.6) | 0.742 | <0.0017 | 22 | + | 5: 128,328,505–128,329,501 |
| SLC03A1 | 73.9 (51.6–89.7) | 83.3 (67.1–93.3) | 0.797 | <0.0001 | 333 | + | 15: 90,196,981–90,198,831 |
| SPSB4 | 82.6 (61.2–95.0) | 80.6 (63.9–91.8) | 0.824 | <0.0001 | 91 | + | 3: 142,252,136–142,254,676 |
| STAT3 | 69.5 (47.0–86.7) | 69.4 (51.8–83.6) | 0.744 | <0.0017 | 757 | − | 17: 37,794,547–37,794,828 |
| SYN2 | 73.9 (51.6–89.7) | 80.5 (63.9–91.8) | 0.809 | <0.0001 | 406 | + | 3: 12,020,118–12,021,768 |
| TACR3 | 69.5 (47.0–86.7) | 72.2 (54.8–85.8) | 0.704 | <0.0086 | 346 | − | 4: 104,860,449–104,860,859 |
| TIRAP | 73.9 (51.6–89.7) | 69.4 (51.9–83.6) | 0.779 | <0.0003 | 645 | + | 11: 125,657,511–125,658,777 |
| WNT11 | 65.22 (42.7–83.6) | 63.9 (46.2–79.2) | 0.753 | <0.0011 | 221 | − | 11: 75,594,610–75,600,053 |
NOTE: Performance of the genes was analyzed by AUC of the genes for the 2 contrast groups. Sensitivity and specificity are reported for the threshold that minimized sensitivity–specificity. The P value indicates the statistical significance. Location of the CpG site used for analysis is given with respect to the distance from the transcription start site. The CpG island location on the respective chromosome is shown.
Abbreviation: CI, confidence interval.
↵at test P value is obtained by comparing tumor (n = 158) and benign tissues (n = 34).
↵bt test P value is obtained by comparing prostate cancer tissues of patients with recurrence (n = 98) and without recurrence (n = 60).
↵ct test P value is obtained by comparing prostate cancer tissues of patients with clinical recurrence (n = 59) and biochemical recurrence (n = 39).
↵dt test P value is obtained by comparing prostate cancer tissues of patients with systemic recurrence (n = 23) and local recurrence (n = 36).