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://www.wjon.org

Original Article

Volume 15, Number 4, August 2024, pages 612-624

High Probability of Lynch Syndrome Among Colorectal Cancer Patients Is Associated With Higher Occurrence of KRAS and PIK3CA Mutations

Figure 1. Kaplan-Meier overall survival curves of CRC patients. (a) Overall survival comparison based on PIK3CA mutation and probable Lynch syndrome status. (b) Overall survival comparison based on KRAS mutation and probable Lynch syndrome status.

**Table 1.** KRAS and PIK3CA With MSI Mutational Status
Characteristic	MSI
^an (%). ^bFisher’s exact test. *P-value < 0.05. MSI: microsatellite instability.
KRAS				0.038*
Mutant	151 (61.88%)	32 (76.19%)	119 (58.91%)
Wild-type	93 (38.11%)	10 (23.81%)	83 (41.09%)
KRAS CO BRAF				0.7
Yes	14 (5.73%)	3 (7.14%)	11 (5.45%)
No	230 (94.26%)	39 (92.86%)	191 (94.55%)
PIK3CA				0.027*
Mutant	107 (43.85%)	25 (59.52%)	82 (40.59%)
Wild-type	137 (56.14%)	17 (40.48%)	120 (59.41%)

Table 1. KRAS and PIK3CA With MSI Mutational Status

Characteristic

MSI

Overall, N = 244^a

MSI, N = 42^a

MSS, N = 202^a

P-value^b

^an (%). ^bFisher’s exact test. *P-value < 0.05. MSI: microsatellite instability.

KRAS

0.038*

Mutant

151 (61.88%)

32 (76.19%)

119 (58.91%)

Wild-type

93 (38.11%)

10 (23.81%)

83 (41.09%)

KRAS CO BRAF

0.7

Yes

14 (5.73%)

3 (7.14%)

11 (5.45%)

230 (94.26%)

39 (92.86%)

191 (94.55%)

PIK3CA

0.027*

Mutant

107 (43.85%)

25 (59.52%)

82 (40.59%)

Wild-type

137 (56.14%)

17 (40.48%)

120 (59.41%)

**Table 2.** KRAS, PIK3CA and Probable Lynch Status
Characteristic	Probable Lynch
^an (%). ^bFisher’s exact test. *P-value < 0.05.
KRAS				0.018*
Mutant	138 (61.88%)	26 (81.25%)	112 (58.64%)
Wild-type	85 (38.12%)	6 (18.75%)	79 (41.36%)
PIK3CA				0.13
Mutant	103 (46.19%)	19 (59.38%)	84 (43.98%)
Wild-type	120 (53.81%)	13 (40.63%)	107 (56.02%)

Table 2. KRAS, PIK3CA and Probable Lynch Status

Characteristic

Probable Lynch

Overall, N = 223^a

Yes, N = 32^a

No, N = 191^a

P-value^b

^an (%). ^bFisher’s exact test. *P-value < 0.05.

KRAS

0.018*

Mutant

138 (61.88%)

26 (81.25%)

112 (58.64%)

Wild-type

85 (38.12%)

6 (18.75%)

79 (41.36%)

PIK3CA

0.13

Mutant

103 (46.19%)

19 (59.38%)

84 (43.98%)

Wild-type

120 (53.81%)

13 (40.63%)

107 (56.02%)

**Table 3.** Clinicopathology Association With PIK3CA and KRAS Oncogene Status
Characteristic	Overall, N = 244^a	PIK3CA	KRAS
^an (%). ^bFisher’s exact test. *P-value < 0.05. BMI: body mass index; ECOG: Eastern Cooperative Oncology Group; TILs: tumor-infiltrating lymphocytes.
Age				0.8			0.3
< 50	53 (21.72%)	22 (20.56%)	31 (22.63%))		36 (23.84%)	17 (18.28%)
≥ 50	191 (78.28%)	85 (79.44%)	106 (77.37%)		115 (76.16%)	76 (81.72%)
Sex				0.040*			0.6
Female	123 (50.41%)	62 (57.94%)	61 (44.53%)		74 (49.01%)	49 (52.69%)
Male	121 (49.59%)	45 (42.06%)	76 (55.47%)		77 (50.99%)	44 (47.31%)
Tumor site				0.083			0.022*
Left	192 (79.01%)	79 (73.83%)	113 (83.09%)		112 (74.17%)	80 (86.96%)
Right	51 (20.99%)	28 (26.17%)	23 (16.91%)		39 (25.83%)	12 (13.04%)
Unknown	1	0	1		0	1
Stage				0.6			> 0.9
I	12 (5.08%)	5 (4.76%)	7 (5.34%)		7 (4.86%)	5 (5.43%)
II	70 (29.66%)	33 (31.43%)	37 (28.24%)		43 (29.86%)	27 (29.35%)
III	56 (23.73%)	28 (26.67%)	28 (21.37%)		35 (24.31%)	21 (22.83%)
IV	98 (41.53%)	39 (37.14%)	59 (45.04%)		59 (40.97%)	39 (42.39%)
Unknown	8	2	6		7	1
Tumor (T) status				> 0.9			> 0.9
1	3 (1.23%)	1 (0.94%)	2 (1.46%)		2 (1.33%)	1 (1.08%)
2	25 (10.29%)	10 (9.43%)	15 (10.95%)		17 (11.33%)	8 (8.60%)
3	156 (64.20%)	71 (66.98%)	85 (62.04%)		94 (62.67%)	62 (66.67%)
4	59 (24.28%)	24 (22.64%)	35 (25.55%)		37 (24.67%)	22 (23.66%)
Unknown	1	1	0		1	0
Lymph node (N) status				0.3			0.7
0	121 (51.05%)	49 (46.67%)	72 (54.55%)		77 (53.10%)	44 (47.83%)
1	84 (35.44%)	38 (36.19%)	46 (34.85%)		49 (33.79%)	35 (38.04%)
2	32 (13.50%)	18 (17.14%)	14 (10.61%)		19 (13.10%)	13 (14.13%)
Unknown	7	2	5		6	1
Metastasis (M) status				0.3			0.8
0	139 (58.90%)	66 (62.86%)	73 (55.73%)		86 (59.72%)	53 (57.61%)
1	97 (41.10%)	39 (37.14%)	58 (44.27%)		58 (40.28%)	39 (42.39%)
Unknown	8	2	6		7	1
Histological grading				0.4			0.038*
1	107 (44.77%)	47 (45.19%)	60 (44.44%)		67 (45.89%)	40 (43.01%)
2	99 (41.42%)	40 (38.46%)	59 (43.70%)		55 (37.67%)	44 (47.31%)
3	31 (12.97%)	17 (16.35%)	14 (10.37%)		24 (16.44%)	7 (7.53%)
4	2 (0.84%)	0 (0.00%)	2 (1.48%)		0 (0.00%)	2 (2.15%)
Unknown	5	3	2		5	0
Lymphovascular invasion status				0.3			> 0.9
0	51 (46.36%)	27 (51.92%)	24 (41.38%)		29 (46.77%)	22 (45.83%)
1	59 (53.64%)	25 (48.08%)	34 (58.62%)		33 (53.23%)	26 (54.17%)
Unknown	134	55	79		89	45
Pathological morphology				0.2			0.7
Adenocarcinoma	239 (97.95%)	103 (96.26%)	136 (99.27%)		147 (97.35%)	92 (98.92%)
Mucinous carcinoma	5 (2.05%)	4 (3.74%)	1 (0.73%)		4 (2.65%)	1 (1.08%)
TILs				0.023*			0.6
High	80 (39.41%)	26 (30.23%)	54 (46.15%)		46 (36.80%)	34 (43.59%)
Medium	78 (38.42%)	34 (39.53%)	44 (37.61%)		51 (40.80%)	27 (34.62%)
Low	45 (22.17%)	26 (30.23%)	19 (16.24%)		28 (22.40%)	17 (21.79%)
Unknown	41	21	20		26	15
BMI (kg/m²)				0.3			0.081
< 18.5	72 (30.77%)	33 (32.67%)	39 (29.32%)		42 (28.97%)	30 (33.71%)
≥ 25	33 (14.10%)	18 (17.82%)	15 (11.28%)		18 (12.41%)	15 (16.85%)
18.5 - 22.9	97 (41.45%)	36 (35.64%)	61 (45.86%)		69 (47.59%)	28 (31.46%)
23 - 24.9	32 (13.68%)	14 (13.86%)	18 (13.53%)		16 (11.03%)	16 (17.98%)
Unknown	10	6	4		6	4
Hemoglobin level (g/dL)				> 0.9			0.9
< 10	48 (20.51%)	21 (20.59%)	27 (20.45%)		30 (21.13%)	18 (19.57%)
≥ 10	186 (79.49%)	81 (79.41%)	105 (79.55%)		112 (78.87%)	74 (80.43%)
Unknown	10	5	5		9	1
ECOG		0.5			0.7
0 - 1	154 (73.33%)	72 (75.79%)	82 (71.30%)		98 (75.38%)	56 (70.00%)
2	38 (18.10%)	14 (14.74%)	24 (20.87%)		22 (16.92%)	16 (20.00%)
3 - 4	18 (8.57%)	9 (9.47%)	9 (7.83%)		10 (7.69%)	8 (10.00%)
Unknown	34	12	22		21	13

Table 3. Clinicopathology Association With PIK3CA and KRAS Oncogene Status

Characteristic

Overall, N = 244^a

PIK3CA

KRAS

Mutant, N = 107^a

Wild-type, N = 137^a

P-value^b

Mutant, N = 151^a

Wild-type, N = 93^a

P-value^b

^an (%). ^bFisher’s exact test. *P-value < 0.05. BMI: body mass index; ECOG: Eastern Cooperative Oncology Group; TILs: tumor-infiltrating lymphocytes.

Age

0.8

0.3

< 50

53 (21.72%)

22 (20.56%)

31 (22.63%))

36 (23.84%)

17 (18.28%)

≥ 50

191 (78.28%)

85 (79.44%)

106 (77.37%)

115 (76.16%)

76 (81.72%)

Sex

0.040*

0.6

Female

123 (50.41%)

62 (57.94%)

61 (44.53%)

74 (49.01%)

49 (52.69%)

Male

121 (49.59%)

45 (42.06%)

76 (55.47%)

77 (50.99%)

44 (47.31%)

Tumor site

0.083

0.022*

Left

192 (79.01%)

79 (73.83%)

113 (83.09%)

112 (74.17%)

80 (86.96%)

Right

51 (20.99%)

28 (26.17%)

23 (16.91%)

39 (25.83%)

12 (13.04%)

Unknown

Stage

0.6

> 0.9

12 (5.08%)

5 (4.76%)

7 (5.34%)

7 (4.86%)

5 (5.43%)

70 (29.66%)

33 (31.43%)

37 (28.24%)

43 (29.86%)

27 (29.35%)

III

56 (23.73%)

28 (26.67%)

28 (21.37%)

35 (24.31%)

21 (22.83%)

98 (41.53%)

39 (37.14%)

59 (45.04%)

59 (40.97%)

39 (42.39%)

Unknown

Tumor (T) status

> 0.9

3 (1.23%)

1 (0.94%)

2 (1.46%)

2 (1.33%)

1 (1.08%)

25 (10.29%)

10 (9.43%)

15 (10.95%)

17 (11.33%)

8 (8.60%)

156 (64.20%)

71 (66.98%)

85 (62.04%)

94 (62.67%)

62 (66.67%)

59 (24.28%)

24 (22.64%)

35 (25.55%)

37 (24.67%)

22 (23.66%)

Unknown

Lymph node (N) status

0.3

0.7

121 (51.05%)

49 (46.67%)

72 (54.55%)

77 (53.10%)

44 (47.83%)

84 (35.44%)

38 (36.19%)

46 (34.85%)

49 (33.79%)

35 (38.04%)

32 (13.50%)

18 (17.14%)

14 (10.61%)

19 (13.10%)

13 (14.13%)

Unknown

Metastasis (M) status

0.3

0.8

139 (58.90%)

66 (62.86%)

73 (55.73%)

86 (59.72%)

53 (57.61%)

97 (41.10%)

39 (37.14%)

58 (44.27%)

58 (40.28%)

39 (42.39%)

Unknown

Histological grading

0.4

0.038*

107 (44.77%)

47 (45.19%)

60 (44.44%)

67 (45.89%)

40 (43.01%)

99 (41.42%)

40 (38.46%)

59 (43.70%)

55 (37.67%)

44 (47.31%)

31 (12.97%)

17 (16.35%)

14 (10.37%)

24 (16.44%)

7 (7.53%)

2 (0.84%)

0 (0.00%)

2 (1.48%)

0 (0.00%)

2 (2.15%)

Unknown

Lymphovascular invasion status

0.3

> 0.9

51 (46.36%)

27 (51.92%)

24 (41.38%)

29 (46.77%)

22 (45.83%)

59 (53.64%)

25 (48.08%)

34 (58.62%)

33 (53.23%)

26 (54.17%)

Unknown

134

Pathological morphology

0.2

0.7

Adenocarcinoma

239 (97.95%)

103 (96.26%)

136 (99.27%)

147 (97.35%)

92 (98.92%)

Mucinous carcinoma

5 (2.05%)

4 (3.74%)

1 (0.73%)

4 (2.65%)

1 (1.08%)

TILs

0.023*

0.6

High

80 (39.41%)

26 (30.23%)

54 (46.15%)

46 (36.80%)

34 (43.59%)

Medium

78 (38.42%)

34 (39.53%)

44 (37.61%)

51 (40.80%)

27 (34.62%)

Low

45 (22.17%)

26 (30.23%)

19 (16.24%)

28 (22.40%)

17 (21.79%)

Unknown

BMI (kg/m²)

0.3

0.081

< 18.5

72 (30.77%)

33 (32.67%)

39 (29.32%)

42 (28.97%)

30 (33.71%)

≥ 25

33 (14.10%)

18 (17.82%)

15 (11.28%)

18 (12.41%)

15 (16.85%)

18.5 - 22.9

97 (41.45%)

36 (35.64%)

61 (45.86%)

69 (47.59%)

28 (31.46%)

23 - 24.9

32 (13.68%)

14 (13.86%)

18 (13.53%)

16 (11.03%)

16 (17.98%)

Unknown

Hemoglobin level (g/dL)

> 0.9

0.9

< 10

48 (20.51%)

21 (20.59%)

27 (20.45%)

30 (21.13%)

18 (19.57%)

≥ 10

186 (79.49%)

81 (79.41%)

105 (79.55%)

112 (78.87%)

74 (80.43%)

Unknown

ECOG

0.5

0.7

0 - 1

154 (73.33%)

72 (75.79%)

82 (71.30%)

98 (75.38%)

56 (70.00%)

38 (18.10%)

14 (14.74%)

24 (20.87%)

22 (16.92%)

16 (20.00%)

3 - 4

18 (8.57%)

9 (9.47%)

9 (7.83%)

10 (7.69%)

8 (10.00%)

Unknown