Figure 1. CISD1 expression correlated with life span. CISD1 expression varied in different cancers. (A) CISD1 expression level in non-paired; and (B) paired breast cancer samples; (C) Association between Overall Survival and CISD1 expression; (D) Verification of high-level; and (E) low-level; (F) expression of CISD1 in Human Protein Atlas. “ns”, “*”, “**”, and “***” represented no significance, p-values < 0.05, 0.01, and 0.001, respectively.

Figure 1. CISD1 expression correlated with life span. CISD1 expression varied in different cancers. (A) CISD1 expression level in non-paired; and (B) paired breast cancer samples; (C) Association between Overall Survival and CISD1 expression; (D) Verification of high-level; and (E) low-level; (F) expression of CISD1 in Human Protein Atlas. “ns”, “*”, “**”, and “***” represented no significance, p-values < 0.05, 0.01, and 0.001, respectively.

Figure 2. Correlation between the clinical features and CISD1 expression. Boxplots represented correlation between the CISD1 expression and ER status (A), HER2 status (B), PR status (C), PAM50 (D), pathologic stage (E), histological type (F), M stage (G), T stage (H), Menopause status (I). “ns”, “**”, and “***” represented no significance, p-values < 0.01, and 0.001, respectively.

Figure 2. Correlation between the clinical features and CISD1 expression. Boxplots represented correlation between the CISD1 expression and ER status (A), HER2 status (B), PR status (C), PAM50 (D), pathologic stage (E), histological type (F), M stage (G), T stage (H), Menopause status (I). “ns”, “**”, and “***” represented no significance, p-values < 0.01, and 0.001, respectively.

Figure 3. CISD1 expression associated with immune cell infiltration. Correlation between CISD1 expression inferred immune cells infiltration (A), pDC (B,C), and NK (D,E) negatively associated with CISD1 expression. “***” represented p-values < 0.001.

Figure 3. CISD1 expression associated with immune cell infiltration. Correlation between CISD1 expression inferred immune cells infiltration (A), pDC (B,C), and NK (D,E) negatively associated with CISD1 expression. “***” represented p-values < 0.001.

Figure 4. Co-expressed genes enrichment and interaction analysis. Co-expressed genes with CISD1 enrichment analysis (A), protein-protein interactions (B), and chemical-protein interactions (C) showed. Stronger associations represented by thicker lines. Chemical-protein interactions in green and interactions between chemicals in red.

Figure 4. Co-expressed genes enrichment and interaction analysis. Co-expressed genes with CISD1 enrichment analysis (A), protein-protein interactions (B), and chemical-protein interactions (C) showed. Stronger associations represented by thicker lines. Chemical-protein interactions in green and interactions between chemicals in red.

Figure 5. Shared genes between the co-expression genes with CISD1 and “diabetes mellitus”. A Venn diagram of shared genes between the co-expressed genes with CISD1 and “diabetes mellitus” (A); Protein-protein interaction network of the shared genes (B); and prediction of the transcription factors of the shared genes (C).

Figure 5. Shared genes between the co-expression genes with CISD1 and “diabetes mellitus”. A Venn diagram of shared genes between the co-expressed genes with CISD1 and “diabetes mellitus” (A); Protein-protein interaction network of the shared genes (B); and prediction of the transcription factors of the shared genes (C).

Figure 6. Gene enrichment analysis of the shared genes between genes co-expressed with CISD1 and “diabetes mellitus”. Pathways and functional terms enrichment results (A); Relationships of the terms listed by color (B); and p-value (C). Densely connected MCODE networks (D); and detailed MCODE networks (E).

Figure 6. Gene enrichment analysis of the shared genes between genes co-expressed with CISD1 and “diabetes mellitus”. Pathways and functional terms enrichment results (A); Relationships of the terms listed by color (B); and p-value (C). Densely connected MCODE networks (D); and detailed MCODE networks (E).

Table 1. Breast cancer clinicopathological characteristics and CISD1 expression.

Table 1. Breast cancer clinicopathological characteristics and CISD1 expression.

CharacteristicLow Expression of CISD1High Expression of CISD1pn541542 T stage, n (%) 0.075T1148 (13.7%)129 (11.9%) T2296 (27.4%)333 (30.8%) T380 (7.4%)59 (5.5%) T416 (1.5%)19 (1.8%) N stage, n (%) 0.012N0266 (25%)248 (23.3%) N1175 (16.4%)183 (17.2%) N245 (4.2%)71 (6.7%) N347 (4.4%)29 (2.7%) M stage, n (%) 0.047M0451 (48.9%)451 (48.9%) M15 (0.5%)15 (1.6%) Pathologic stage, n (%) 0.099Stage I101 (9.5%)80 (7.5%) Stage II304 (28.7%)315 (29.7%) Stage III124 (11.7%)118 (11.1%) Stage IV5 (0.5%)13 (1.2%) Race, n (%) <0.001Asian23 (2.3%)37 (3.7%) Black or African American70 (7%)111 (11.2%) White405 (40.7%)348 (35%) Age, n (%) 0.022≤60281 (25.9%)320 (29.5%) >60260 (24%)222 (20.5%) Histological type, n (%) <0.001Infiltrating Ductal Carcinoma346 (35.4%)426 (43.6%) Infiltrating Lobular Carcinoma139 (14.2%)66 (6.8%) PR status, n (%) <0.001Negative145 (14%)197 (19.1%) Indeterminate3 (0.3%)1 (0.1%) Positive371 (35.9%)317 (30.7%) ER status, n (%) <0.001Negative90 (8.7%)150 (14.5%) Indeterminate0 (0%)2 (0.2%) Positive430 (41.5%)363 (35.1%) HER2 status, n (%) 0.647Negative290 (39.9%)268 (36.9%) Indeterminate6 (0.8%)6 (0.8%) Positive75 (10.3%)82 (11.3%) PAM50, n (%) <0.001Normal23 (2.1%)17 (1.6%) LumA338 (31.2%)224 (20.7%) LumB84 (7.8%)120 (11.1%) Her233 (3%)49 (4.5%) Basal63 (5.8%)132 (12.2%) Menopause status, n (%) 0.280Pre105 (10.8%)124 (12.8%) Peri19 (2%)21 (2.2%) Post364 (37.4%)339 (34.9%) Age, median (IQR)60 (50, 68)57 (48, 66)0.013

Table 2. CISD1 expression correlation with immune cells infiltration.

Table 2. CISD1 expression correlation with immune cells infiltration.

Cell TypeCorrelation
(Pearson)p
(Pearson)Correlation
(Spearman)p
(Spearman)aDC0.169<0.0010.142<0.001B cells0.0790.0090.0750.012CD8 T cells0.0660.027−0.0550.067Cytotoxic cells0.0620.0390.0140.646DC0.0780.0100.0180.552Eosinophils−0.0880.003−0.118<0.001iDC0.0230.445−0.0420.161Macrophages0.175<0.0010.145<0.001Mast cells−0.0030.910−0.0410.168Neutrophils0.118<0.0010.0610.041NK CD56bright cells−0.0650.031−0.109<0.001NK CD56dim cells0.154<0.0010.122<0.001NK cells−0.0870.004−0.184<0.001pDC−0.201<0.001−0.231<0.001T cells0.0730.0150.0390.197T helper cells0.0560.0640.0840.005Tcm−0.0410.1680.0160.585Tem0.0650.0300.0790.008TFH0.0370.215−0.0140.639Tgd0.134<0.0010.128<0.001Th1 cells0.240<0.0010.216<0.001Th17 cells−0.141<0.001−0.177<0.001Th2 cells0.282<0.0010.305<0.001TReg0.111<0.0010.0970.001

Table 3. Summary of enrichment analysis in transcription factor targets.

Table 3. Summary of enrichment analysis in transcription factor targets.

GODescriptionCount%Log10(P)Log10(q)M30019HSD17B8 TARGET GENES2216.00−12.00−9.20M19064E2F Q6118.00−7.90−5.10M10115E2F Q4118.00−7.90−5.10M29943DLX6 TARGET GENES1612.00−7.80−5.00M12497E2F Q3107.20−7.00−4.40M5768E2F1DP1RB 01107.20−6.90−4.30M9279E2F1 Q6107.20−6.80−4.20M12402E2F1DP1 01107.20−6.80−4.20M12555E2F1DP2 01107.20−6.80−4.20M17867E2F 02107.20−6.80−4.20M19298E2F4DP2 01107.20−6.80−4.20M10526E2F4DP1 01107.20−6.70−4.20M1485E2F1 Q3107.20−6.70−4.10M8998E2F1 Q4 0196.50−5.90−3.40M17117E2F Q3 0196.50−5.80−3.40M3037E2F1 Q6 0196.50−5.70−3.30M29995HES4 TARGET GENES139.40−5.40−3.00M40770ATXN7L3 TARGET GENES96.50−5.20−2.80M1905SGCGSSAAA E2F1DP2 0175.10−4.90−2.60M102E2F Q4 0185.80−4.80−2.60

Table 4. Top 3 MCODE terms identified.

Table 4. Top 3 MCODE terms identified.

MCODEGODescriptionLog10(P)MCODE_1R−HSA−69613p53−Independent G1/S DNA damage checkpoint−32.6MCODE_1R−HSA−69610p53−Independent DNA Damage Response−32.6MCODE_1R−HSA−69601Ubiquitin Mediated Degradation of Phosphorylated Cdc25A−32.6MCODE_2M176PID FOXM1 PATHWAY−14.5MCODE_2GO:0044772mitotic cell cycle phase transition−12.9MCODE_2GO:0044770cell cycle phase transition−12.7MCODE_3GO:0033365protein localization to organelle−5.8MCODE_3GO:0048285organelle fission−5.5MCODE_3GO:0000819sister chromatid segregation−4.9MCODE_4hsa03008Ribosome biogenesis in eukaryotes−9.9MCODE_4GO:0022613ribonucleoprotein complex biogenesis−8.5MCODE_4R−HSA−6790901rRNA modification in the nucleus and cytosol−8.5MCODE_5WP4016DNA IR−damage and cellular response via ATR−10.5MCODE_5WP4946DNA repair pathways, full network−7.3MCODE_5M258PID BARD1 PATHWAY−7MCODE_6R−HSA−5358565Mismatch repair (MMR) directed by MSH2:MSH6 (MutSalpha)−12MCODE_6R−HSA−5358508Mismatch Repair−11.9MCODE_6CORUM:286PCNA−MSH2−MSH6 complex−11.1