World J Oncol

World Journal of Oncology, ISSN 1920-4531 print, 1920-454X online, Open Access

Article copyright, the authors; Journal compilation copyright, World J Oncol and Elmer Press Inc

Journal website https://wjon.elmerpub.com

Original Article

Volume 17, Number 3, June 2026, pages 310-321

Incidence and Prognostic Value of TP53, STK11, and KEAP1 Mutations Between De Novo Versus Recurrent Actionable Mutation–Negative Non-Small Cell Lung Cancer: A Single-Center Retrospective Study

↓ Figure 2. Multivariable Cox regression results for PFS for selected variables. No variable was noted to be a significant predictor of PFS. PFS: progression-free survival.

↓ Figure 3. Multivariable Cox regression results for OS for selected variables. No variable was noted to be a significant predictor of OS. OS: overall survival.

↓ Figure 4. Overall survival according to mutation status. Kaplan–Meier survival analysis showed no significant survival differences according to TP53, STK11, and KEAP1 mutation status. (a) De novo group. (b) Recurrent group.

↓ Figure 5. Progression-free survival according to mutation status. Kaplan–Meier survival analysis showed no significant survival differences according to TP53, STK11, and KEAP1 mutation status. (a) De novo group. (b) Recurrent group.

↓ Figure 6. Overall and progression-free survival according to co-mutation status in the overall cohort. (a and c) TP53 with co-mutations in KEAP1 and STK11. (b and d) KEAP1 and STK11 co-mutations. Kaplan–Meier survival analysis demonstrated longer overall and progression-free survival in patients with TP53–KEAP1 and KEAP1–STK11 co-mutations compared with those harboring single-gene mutations.

↓ **Table 1.** Clinical Characteristics of Study Population
Factors	De novo (n = 82)	Recurrent (n = 37)	P value
Age at diagnosis
Mean	68.1	68.6	0.67
Smoking status
Never	11 (13%)	3 (8%)	0.7
Former	50 (61%)	25 (67%)
Current	21 (26%)	9 (25%)
Sex
Male	48 (58%)	26 (70%)	0.31
Female	34 (42%)	11 (30%)
Race
White NH	74 (90%)	32 (87%)	0.54
Other	8 (10%)	5 (13%)
ECOG at diagnosis
0	26 (32%)	15 (41%)	0.63
1	34 (41%)	12 (32%)
2	10 (12%)	6 (16%)
3	7 (9%)	1 (3%)
4	1 (1%)	0
Unknown	4 (5%)	3 (8%)
Number of comorbidities
Mean	2.3	2.1	0.47
Family history of lung cancer
Yes	17 (21%)	13 (35%)	0.11
No	65 (79%)	24 (65%)
Histology
Adeno	47 (57%)	21 (57%)	0.48
Squamous	22 (27%)	13 (35%)
Others/unknown	16 (16%)	3 (8%)
Stage on diagnosis
I	3 (4%)	17 (46%)	< 0.001
II	5 (6%)	11 (30%)
III	22 (27%)	8 (22%)
IV	52 (63%)	1 (2%)
Surgery
Yes	7 (8%)	21 (57%)	< 0.001
No	75 (92%)	16 (43%)
Radiation
Yes	55(67%)	27 (73%)	0.66
No	27 (33%)	10 (27%)
Chemotherapy
Yes	54 (66%)	32 (86%)	0.02
No	28 (34%)	5 (13.5%)
Immunotherapy
Yes	53 (65%)	26 (70%)	0.68
No	29 (35%)	11 (30%)
PD-L1 (22c3) expression
Absent/0%	42 (51%)	17 (46%)	0.73
1–49%	23 (28%)	13 (35%)
50–100%	17 (21%)	7 (19%)
TP53 status
Mutated	50 (61%)	20 (54%)	0.54
Wild-type	32 (39%)	17 (46%)
STK11 status
Mutated	8 (10%)	2 (5%)	0.72
Wild-type	74 (90%)	35 (95%)
KEAP1 status
Mutated	9 (11%)	6 (16%)	0.55
Wild-type	73 (89%)	31 (84%)
KEAP1–STK11 co-mutation
Yes	3 (4%)	2 (5%)	0.66
No	79 (96%)	35 (95%)
TP53–STK11 co-mutation			0.31
Yes	4 (5%)	0
No	78 (95%)	37 (100%)
TP53–KEAP1 co-mutation
Yes	5 (6%)	4 (11%)	0.66
No	77 (94%)	33 (89%)

↓ Table 1. Clinical Characteristics of Study Population

Factors

De novo (n = 82)

Recurrent (n = 37)

P value

Age at diagnosis

Mean

68.1

68.6

0.67

Smoking status

Never

11 (13%)

3 (8%)

0.7

Former

50 (61%)

25 (67%)

Current

21 (26%)

9 (25%)

Sex

Male

48 (58%)

26 (70%)

0.31

Female

34 (42%)

11 (30%)

Race

White NH

74 (90%)

32 (87%)

0.54

Other

8 (10%)

5 (13%)

ECOG at diagnosis

26 (32%)

15 (41%)

0.63

34 (41%)

12 (32%)

10 (12%)

6 (16%)

7 (9%)

1 (3%)

1 (1%)

Unknown

4 (5%)

3 (8%)

Number of comorbidities

Mean

2.3

2.1

0.47

Family history of lung cancer

Yes

17 (21%)

13 (35%)

0.11

65 (79%)

24 (65%)

Histology

Adeno

47 (57%)

21 (57%)

0.48

Squamous

22 (27%)

13 (35%)

Others/unknown

16 (16%)

3 (8%)

Stage on diagnosis

3 (4%)

17 (46%)

< 0.001

5 (6%)

11 (30%)

III

22 (27%)

8 (22%)

52 (63%)

1 (2%)

Surgery

Yes

7 (8%)

21 (57%)

< 0.001

75 (92%)

16 (43%)

Radiation

Yes

55(67%)

27 (73%)

0.66

27 (33%)

10 (27%)

Chemotherapy

Yes

54 (66%)

32 (86%)

0.02

28 (34%)

5 (13.5%)

Immunotherapy

Yes

53 (65%)

26 (70%)

0.68

29 (35%)

11 (30%)

PD-L1 (22c3) expression

Absent/0%

42 (51%)

17 (46%)

0.73

1–49%

23 (28%)

13 (35%)

50–100%

17 (21%)

7 (19%)

TP53 status

Mutated

50 (61%)

20 (54%)

0.54

Wild-type

32 (39%)

17 (46%)

STK11 status

Mutated

8 (10%)

2 (5%)

0.72

Wild-type

74 (90%)

35 (95%)

KEAP1 status

Mutated

9 (11%)

6 (16%)

0.55

Wild-type

73 (89%)

31 (84%)

KEAP1–STK11 co-mutation

Yes

3 (4%)

2 (5%)

0.66

79 (96%)

35 (95%)

TP53–STK11 co-mutation

0.31

Yes

4 (5%)

78 (95%)

37 (100%)

TP53–KEAP1 co-mutation

Yes

5 (6%)

4 (11%)

0.66

77 (94%)

33 (89%)

↓ **Table 2.** STK11 and KEAP1 Co-Mutation Frequencies
Group	De novo (n = 82)	Recurrent (n = 37)
Neg: negative; OR: odds ratio; Pos: positive.
KEAP1 Neg	68 (93%)	5 (7%)	0.03	6.53 (0.82–45.01)	31 (100%)	0	0.02	NA
KEAP1 Pos	6 (67%)	3 (33%)			4 (67%)	2 (33%)

↓ Table 2. STK11 and KEAP1 Co-Mutation Frequencies

Group

De novo (n = 82)

Recurrent (n = 37)

STK11 Neg

STK11 Pos

P value

STK11 Neg

STK11 Pos

P value

Neg: negative; OR: odds ratio; Pos: positive.

KEAP1 Neg

68 (93%)

5 (7%)

0.03

6.53 (0.82–45.01)

31 (100%)

0.02

KEAP1 Pos

6 (67%)

3 (33%)

4 (67%)

2 (33%)

↓ **Table 3.** TP53 and STK11–KEAP1 Co-Mutation Frequencies
Group
Neg: negative; OR: odds ratio; Pos: positive.
De novo (n = 82)
TP53 Neg	35 (90%)	4 (10%)	1	0.89 (0.22–3.58)	34 (89%)	4 (11%)	1	1.07 (0.28–4.02)
TP53 Pos	39 (91%)	4 (9%)			39 (89%)	5 (11%)
Recurrent (n = 37)
TP53 Neg	19 (90%)	2 (10%)	0.5	0.24 (0.01–5.28)	15 (88%)	2 (12%)	0.66	1.7 (0.31–9.2)
TP53 Pos	16 (100%)	0			16 (80%)	4 (20%)

↓ Table 3. TP53 and STK11–KEAP1 Co-Mutation Frequencies

Group

STK11 Neg

STK11 Pos

P value

KEAP1 Neg

KEAP Pos

P value

Neg: negative; OR: odds ratio; Pos: positive.

De novo (n = 82)

TP53 Neg

35 (90%)

4 (10%)

0.89 (0.22–3.58)

34 (89%)

4 (11%)

1.07 (0.28–4.02)

TP53 Pos

39 (91%)

4 (9%)

39 (89%)

5 (11%)

Recurrent (n = 37)

TP53 Neg

19 (90%)

2 (10%)

0.5

0.24 (0.01–5.28)

15 (88%)

2 (12%)

0.66

1.7 (0.31–9.2)

TP53 Pos

16 (100%)

16 (80%)

4 (20%)

↓ **Table 4.** Univariate Cox Regression Results for Selected Variables
Factors	OS (HR)	PFS (HR)
HR: hazard ratio; OS: overall survival; PFS: progression-free survival; WT: wild-type.
Age at diagnosis	1.01 (1–1.03) P = 0.22	0.989 (0.97–1.009) P = 0.28
Number of comorbidities	1.27 (1.09–1.47) P = 0.001	1.14 (1.001–1.29) P = 0.04
Sex (female vs. male)	0.73 (0.44–1.19) P = 0.2	0.84 (0.55–1.26) P = 0.39
Race (non-White vs. White)	1.14 (0.55–2.4) P = 0.72	1.04 (0.55–2) P = 0.90
TP53 status (mutated vs. WT)	1.21 (0.75–1.95) P = 0.44	1.09 (0.73–1.63) P = 0.66
STK11 status (mutated vs. WT)	1.05 (0.42–2.6) P = 0.92	0.94 (0.43–2.02) P = 0.87
KEAP1 status (mutated vs. WT)	0.57 (0.26–1.24) P = 0.16	0.59 (0.30–1.13) P = 0.11
KEAP1–STK1 co-mutation (yes vs. no)	0.55 (0.13–2.26) P = 0.41	0.33 (0.08–1.34) P = 0.12

↓ Table 4. Univariate Cox Regression Results for Selected Variables

Factors

OS (HR)

PFS (HR)

HR: hazard ratio; OS: overall survival; PFS: progression-free survival; WT: wild-type.

Age at diagnosis

1.01 (1–1.03)
P = 0.22

0.989 (0.97–1.009)
P = 0.28

Number of comorbidities

1.27 (1.09–1.47)
P = 0.001

1.14 (1.001–1.29)
P = 0.04

Sex (female vs. male)

0.73 (0.44–1.19)
P = 0.2

0.84 (0.55–1.26)
P = 0.39

Race (non-White vs. White)

1.14 (0.55–2.4)
P = 0.72

1.04 (0.55–2)
P = 0.90

TP53 status (mutated vs. WT)

1.21 (0.75–1.95)
P = 0.44

1.09 (0.73–1.63)
P = 0.66

STK11 status (mutated vs. WT)

1.05 (0.42–2.6)
P = 0.92

0.94 (0.43–2.02)
P = 0.87

KEAP1 status (mutated vs. WT)

0.57 (0.26–1.24)
P = 0.16

0.59 (0.30–1.13)
P = 0.11

KEAP1–STK1 co-mutation (yes vs. no)

0.55 (0.13–2.26)
P = 0.41

0.33 (0.08–1.34)
P = 0.12