Lower Expression of CFTR Is Associated with Higher Mortality in a Meta-Analysis of Individuals with Colorectal Cancer
Abstract
:Simple Summary
Abstract
1. Introduction
2. Materials and Methods
2.1. Study Design
2.2. TCGA COADREAD Study
2.3. GSE39582 and GSE17538 Studies
2.3.1. Patient and Clinical Information in the GSE17538 Study
2.3.2. Patient and Clinical Information in the GSE39582 Study
2.4. Statistical Analysis
3. Results
3.1. Descriptive Analysis
3.2. CFTR Expression and the Risk of Overall Death
3.3. CFTR Expression and the Risk of Disease-Specific Death
3.4. Somatic Mutations in CFTR in CRC
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Characteristics | TCGA COADREAD | GSE17538 | GSE39582 |
---|---|---|---|
Total number (N) of CRC cases 1,2 | 453 (colon: 269; rectal: 87; missing: 97)2 | 204 | 520 |
Age, median (range), years | 67 (31–90) | 65 (23–94) | 68 (22–97) |
Female, N (%) | 213 (47.02) | 101 (49.51) | 231 (44.42) |
Race, N (%) White Black Asian Hispanic Other/Missing | 228 (50.33) 54 (1.92) 12 (2.65) — 159 (35.01) | 177 (86.76) 13 (6.37) — 2 (0.98) 12 (5.88) | — |
Stage at diagnosis, N (%) 2 3 4 | 207 (45.70) 165 (36.42) 81 (17.88) | 72 (35.29) 76 (37.25) 56 (27.45) | 258 (49.62) 203 (39.04) 59 (11.35) |
MSI/MSS status,3 N (%) MSI MSS Unknown/Missing | 64 (14.13) 381 (84.11) 8 (1.77) | — | 62 (11.92) 412 (79.23) 46 (8.85) |
Follow-up time median (range), months | 22.36 (0.20–148.01) | 41.49 (0.43–134.86) | 52 (1–201) |
No. of deaths from all causes/CRC | 104/65 | 89/54 | 181/UK |
Dataset | HR (95% CI) across Quartiles (Q1 is Reference) | p-Trend 4 | |||
---|---|---|---|---|---|
TCGA COADREAD | |||||
CFTR Expression | Q1: −1.54–(−0.74) | Q2: −0.73–(−0.07) | Q3: −0.06–0.49 | Q4: 0.49–4.41 | |
Overall death (N) | 33 | 27 | 23 | 21 | |
Person-years (months) | 3005 | 3404 | 3559 | 3111 | |
Model 1 1 (N = 453) Model 2 2 (N = 453) Model 3 3 (N = 356) | 1.00 (Reference) 1.00 (Reference) 1.00 (Reference) | 0.74 (0.45, 1.24) 0.76 (0.45, 1.27) 0.74 (0.40, 1.37) | 0.59 (0.35, 1.00) 0.55 (0.32, 0.95) 0.47 (0.24, 0.93) | 0.61 (0.35, 1.05) 0.77 (0.44, 1.34) 0.71 (0.36, 1.40) | 0.04 0.16 0.17 |
GSE17538 | |||||
CFTR expression | Q1: −1.53–(−0.74) | Q2: −0.64–(−0.07) | Q3: −0.04–0.40 | Q4: 0.50–3.49 | |
Overall death (N) | 29 | 22 | 21 | 17 | |
Person-years | 1895 | 2182 | 2211.27 | 2926 | |
Model 1 1 (N = 204) Model 2 2 (N = 204) | 1.00 (Reference) 1.00 (Reference) | 0.69 (0.39, 1.20) 0.49 (0.27, 0.87) | 0.66 (0.38, 1.17) 0.48 (0.26, 0.86) | 0.43 (0.24, 0.79) 0.31 (0.16, 0.57) | <0.01 <0.01 |
GSE39582 | |||||
CFTR expression | Q1: −4.31–(−0.39) | Q2: −0.39–0.28 | Q3: 0.29–0.71 | Q4: 0.71–1.62 | |
Overall death (N) | 51 | 46 | 46 | 38 | |
Person-years | 6992 | 7187 | 7801 | 7992 | |
Model 1 1 (N = 520) Model 2 2 (N = 520) Model 3 3 (N = 474) | 1.00 (Reference) 1.00 (Reference) 1.00 (Reference) | 0.86 (0.58, 1.28) 0.87 (0.58, 1.30) 0.92 (0.60, 1.42) | 0.82 (0.55, 1.22) 0.77 (0.52, 1.16) 0.76 (0.49, 1.19) | 0.65 (0.43, 0.99) 0.64 (0.42, 0.97) 0.60 (0.38, 0.96) | 0.05 0.03 0.02 |
Dataset | HR (95% CI) across Quartiles (Q1 is Reference) | p-Trend 4 | |||
---|---|---|---|---|---|
TCGA COADREAD | |||||
CFTR Expression | Q1: −1.54–(−0.74) | Q2: −0.73–(−0.07) | Q3: −0.06–0.49 | Q4: 0.49–4.41 | |
Disease-specific death (N) | 20 | 13 | 18 | 14 | |
Person-years (months) | 2855 | 3241 | 3368 | 2897 | |
Model 1 1 (N = 433) Model 2 2 (N = 433) Model 3 3 (N = 336) | 1.00 (Reference) 1.00 (Reference) 1.00 (Reference) | 0.60 (0.30, 1.21) 0.54 (0.27, 1.10) 0.45 (0.19, 1.08) | 0.77 (0.41, 1.46) 0.59 (0.31, 1.13) 0.45 (0.20, 1.04) | 0.69 (0.35, 1.37) 0.74 (0.37, 1.48) 0.62 (0.26, 1.49) | 0.40 0.38 0.39 |
GSE17538 | |||||
CFTR expression | Q1: −3.13–(−0.54) | Q2: −0.46–0.29 | Q3: 0.29–0.68 | Q4: 0.69–1.48 | |
Disease-specific death (N) | 18 | 13 | 13 | 10 | |
Person-years | 1305 | 1470 | 1498 | 2695 | |
Model 1 1 (N = 153) Model 2 2 (N = 153) | 1.00 (Reference) 1.00 (Reference) | 0.69 (0.33, 1.42) 0.68 (0.33, 1.42) | 0.68 (0.33, 1.40) 0.61 (0.29, 1.29) | 0.31 (0.14, 0.68) 0.22 (0.09, 0.47) | <0.01 <0.01 |
CRC Cases | Cases with Mutation Data | Cases with CFTR Mutations | |||
---|---|---|---|---|---|
No. of Cases | 300 | 17 | |||
Somatic CFTR Mutations 2 | Total No. of Mutations | Stop Loss or Gain | Frameshift | Splice Site | Missense |
No. of mutations | 22 | 4 | 3 | 1 | 14 |
CF-causing mutations in CFTR2 3 | 2 | ||||
CRC subtypes of cases with mutations | 4 Cases with subtype data | CIN | MSI | POLE | |
No. of cases | 17 | 4 | 6 | 7 | |
Ave. no. of mutations per case | 97 | 1665 | 5665 |
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Scott, P.; Wang, S.; Onyeaghala, G.; Pankratz, N.; Starr, T.; Prizment, A.E. Lower Expression of CFTR Is Associated with Higher Mortality in a Meta-Analysis of Individuals with Colorectal Cancer. Cancers 2023, 15, 989. https://doi.org/10.3390/cancers15030989
Scott P, Wang S, Onyeaghala G, Pankratz N, Starr T, Prizment AE. Lower Expression of CFTR Is Associated with Higher Mortality in a Meta-Analysis of Individuals with Colorectal Cancer. Cancers. 2023; 15(3):989. https://doi.org/10.3390/cancers15030989
Chicago/Turabian StyleScott, Patricia, Shuo Wang, Guillaume Onyeaghala, Nathan Pankratz, Timothy Starr, and Anna E. Prizment. 2023. "Lower Expression of CFTR Is Associated with Higher Mortality in a Meta-Analysis of Individuals with Colorectal Cancer" Cancers 15, no. 3: 989. https://doi.org/10.3390/cancers15030989