Table 2 Open in new tab Cox regression...

Variables	Univariate analysis	P	Multivariable analysis	P
Disease-free survival
Age (years)	0.991 (0.969,1.012)	0.386
Sex (male versus female)	1.006 (0.651,1.555)	0.979
Preoperative CEA level (elevated versus normal)	1.309 (0.847,2.025)	0.226
SII (high versus low)	2.408 (1.522,3.808)	<0.001	1.946 (1.221,3.102)	0.005
Distance from the anal verge (≥5 cm versus < 5 cm)	0.904 (0.589,1.389)	0.646
Surgical approach (low anterior resection versus other procedures)	0.922 (0.577,1.471)	0.732
Tumour differentiation (poor + moderate versus well)	1.473 (0.874,2.483)	0.146
ypT stage (ypT3–4 versus ypT1–2)	1.636 (1.066,2.510)	0.024	NA	NA
ypN stage (ypN + versus ypN0)	2.229 (1.444,3.443)	<0.001	1.645 (1.046,2.588)	0.031
TRG (TRG 2–3 versus TRG 1)	2.696 (1.600,4.544)	<0.001	2.239 (1.320,3.797)	0.003
Adjuvant treatment (yes versus no)	0.605 (0.264,1.390)	0.236
Collagen signature	3.715 (2.745,5.029)	<0.001	2.965 (2.159,4.073)	<0.001
Overall survival
Age (years)	0.996 (0.794,1.020)	0.764
Sex (male versus female)	1.241 (0.786,1.961)	0.354
Preoperative CEA level (elevated versus normal)	1.422 (0.895,2.259)	0.136
SII (high versus low)	2.167 (1.337,3.510)	0.002	1.707 (1.043,2.795)	0.033
Distance from the anal verge (≥ 5 cm versus <5 cm)	0.927 (0.587,1.465)	0.746
Surgical approach (low anterior resection versus other procedures)	0.924 (0.561,1.522)	0.757
Tumour differentiation (poor + moderate versus well)	1.219 (0.681,2.181)	0.505
ypT stage (ypT3–4 versus ypT1–2)	1.615 (1.024,2.549)	0.039	NA	NA
ypN stage (ypN+ versus ypN0)	2.379 (1.506,3.760)	<0.001	1.659 (1.024,2.688)	0.040
TRG (TRG 2–3 versus TRG 1)	2.093 (1.241,3.530)	0.006	1.780 (1.050,3.019)	0.032
Adjuvant treatment (yes versus no)	0.720 (0.312,1.660)	0.441
Collagen signature	3.524 (2.534,4.902)	<0.001	2.852 (2.004,4.057)	<0.001

Variables

Univariate analysis

Multivariable analysis

HR (95% c.i.)

Disease-free survival

Age (years)

0.991 (0.969,1.012)

0.386

Sex (male versus female)

1.006 (0.651,1.555)

0.979

Preoperative CEA level (elevated versus normal)

1.309 (0.847,2.025)

0.226

SII (high versus low)

2.408 (1.522,3.808)

<0.001

1.946 (1.221,3.102)

0.005

Distance from the anal verge (≥5 cm versus < 5 cm)

0.904 (0.589,1.389)

0.646

Surgical approach (low anterior resection versus other procedures)

0.922 (0.577,1.471)

0.732

Tumour differentiation (poor + moderate versus well)

1.473 (0.874,2.483)

0.146

ypT stage (ypT3–4 versus ypT1–2)

1.636 (1.066,2.510)

0.024

ypN stage (ypN + versus ypN0)

2.229 (1.444,3.443)

<0.001

1.645 (1.046,2.588)

0.031

TRG (TRG 2–3 versus TRG 1)

2.696 (1.600,4.544)

<0.001

2.239 (1.320,3.797)

0.003

Adjuvant treatment (yes versus no)

0.605 (0.264,1.390)

0.236

Collagen signature

3.715 (2.745,5.029)

<0.001

2.965 (2.159,4.073)

<0.001

Overall survival

Age (years)

0.996 (0.794,1.020)

0.764

Sex (male versus female)

1.241 (0.786,1.961)

0.354

Preoperative CEA level (elevated versus normal)

1.422 (0.895,2.259)

0.136

SII (high versus low)

2.167 (1.337,3.510)

0.002

1.707 (1.043,2.795)

0.033

Distance from the anal verge (≥ 5 cm versus <5 cm)

0.927 (0.587,1.465)

0.746

Surgical approach (low anterior resection versus other procedures)

0.924 (0.561,1.522)

0.757

Tumour differentiation (poor + moderate versus well)

1.219 (0.681,2.181)

0.505

ypT stage (ypT3–4 versus ypT1–2)

1.615 (1.024,2.549)

0.039

ypN stage (ypN+ versus ypN0)

2.379 (1.506,3.760)

<0.001

1.659 (1.024,2.688)

0.040

TRG (TRG 2–3 versus TRG 1)

2.093 (1.241,3.530)

0.006

1.780 (1.050,3.019)

0.032

Adjuvant treatment (yes versus no)

0.720 (0.312,1.660)

0.441

Collagen signature

3.524 (2.534,4.902)

<0.001

2.852 (2.004,4.057)

<0.001

Variables	Univariate analysis	P	Multivariable analysis	P
Disease-free survival
Age (years)	0.991 (0.969,1.012)	0.386
Sex (male versus female)	1.006 (0.651,1.555)	0.979
Preoperative CEA level (elevated versus normal)	1.309 (0.847,2.025)	0.226
SII (high versus low)	2.408 (1.522,3.808)	<0.001	1.946 (1.221,3.102)	0.005
Distance from the anal verge (≥5 cm versus < 5 cm)	0.904 (0.589,1.389)	0.646
Surgical approach (low anterior resection versus other procedures)	0.922 (0.577,1.471)	0.732
Tumour differentiation (poor + moderate versus well)	1.473 (0.874,2.483)	0.146
ypT stage (ypT3–4 versus ypT1–2)	1.636 (1.066,2.510)	0.024	NA	NA
ypN stage (ypN + versus ypN0)	2.229 (1.444,3.443)	<0.001	1.645 (1.046,2.588)	0.031
TRG (TRG 2–3 versus TRG 1)	2.696 (1.600,4.544)	<0.001	2.239 (1.320,3.797)	0.003
Adjuvant treatment (yes versus no)	0.605 (0.264,1.390)	0.236
Collagen signature	3.715 (2.745,5.029)	<0.001	2.965 (2.159,4.073)	<0.001
Overall survival
Age (years)	0.996 (0.794,1.020)	0.764
Sex (male versus female)	1.241 (0.786,1.961)	0.354
Preoperative CEA level (elevated versus normal)	1.422 (0.895,2.259)	0.136
SII (high versus low)	2.167 (1.337,3.510)	0.002	1.707 (1.043,2.795)	0.033
Distance from the anal verge (≥ 5 cm versus <5 cm)	0.927 (0.587,1.465)	0.746
Surgical approach (low anterior resection versus other procedures)	0.924 (0.561,1.522)	0.757
Tumour differentiation (poor + moderate versus well)	1.219 (0.681,2.181)	0.505
ypT stage (ypT3–4 versus ypT1–2)	1.615 (1.024,2.549)	0.039	NA	NA
ypN stage (ypN+ versus ypN0)	2.379 (1.506,3.760)	<0.001	1.659 (1.024,2.688)	0.040
TRG (TRG 2–3 versus TRG 1)	2.093 (1.241,3.530)	0.006	1.780 (1.050,3.019)	0.032
Adjuvant treatment (yes versus no)	0.720 (0.312,1.660)	0.441
Collagen signature	3.524 (2.534,4.902)	<0.001	2.852 (2.004,4.057)	<0.001

Table 2

Open in new tab

Cox regression analysis of clinicopathological characteristics and collagen signature for survival in the training cohort

Variables	Univariate analysis	P	Multivariable analysis	P
Variables	HR (95% c.i.)	P	HR (95% c.i.)	P
Disease-free survival
Age (years)	0.991 (0.969,1.012)	0.386
Sex (male versus female)	1.006 (0.651,1.555)	0.979
Preoperative CEA level (elevated versus normal)	1.309 (0.847,2.025)	0.226
SII (high versus low)	2.408 (1.522,3.808)	<0.001	1.946 (1.221,3.102)	0.005
Distance from the anal verge (≥5 cm versus < 5 cm)	0.904 (0.589,1.389)	0.646
Surgical approach (low anterior resection versus other procedures)	0.922 (0.577,1.471)	0.732
Tumour differentiation (poor + moderate versus well)	1.473 (0.874,2.483)	0.146
ypT stage (ypT3–4 versus ypT1–2)	1.636 (1.066,2.510)	0.024	NA	NA
ypN stage (ypN + versus ypN0)	2.229 (1.444,3.443)	<0.001	1.645 (1.046,2.588)	0.031
TRG (TRG 2–3 versus TRG 1)	2.696 (1.600,4.544)	<0.001	2.239 (1.320,3.797)	0.003
Adjuvant treatment (yes versus no)	0.605 (0.264,1.390)	0.236
Collagen signature	3.715 (2.745,5.029)	<0.001	2.965 (2.159,4.073)	<0.001
Overall survival
Age (years)	0.996 (0.794,1.020)	0.764
Sex (male versus female)	1.241 (0.786,1.961)	0.354
Preoperative CEA level (elevated versus normal)	1.422 (0.895,2.259)	0.136
SII (high versus low)	2.167 (1.337,3.510)	0.002	1.707 (1.043,2.795)	0.033
Distance from the anal verge (≥ 5 cm versus <5 cm)	0.927 (0.587,1.465)	0.746
Surgical approach (low anterior resection versus other procedures)	0.924 (0.561,1.522)	0.757
Tumour differentiation (poor + moderate versus well)	1.219 (0.681,2.181)	0.505
ypT stage (ypT3–4 versus ypT1–2)	1.615 (1.024,2.549)	0.039	NA	NA
ypN stage (ypN+ versus ypN0)	2.379 (1.506,3.760)	<0.001	1.659 (1.024,2.688)	0.040
TRG (TRG 2–3 versus TRG 1)	2.093 (1.241,3.530)	0.006	1.780 (1.050,3.019)	0.032
Adjuvant treatment (yes versus no)	0.720 (0.312,1.660)	0.441
Collagen signature	3.524 (2.534,4.902)	<0.001	2.852 (2.004,4.057)	<0.001

Variables	Univariate analysis	P	Multivariable analysis	P
Variables	HR (95% c.i.)	P	HR (95% c.i.)	P
Disease-free survival
Age (years)	0.991 (0.969,1.012)	0.386
Sex (male versus female)	1.006 (0.651,1.555)	0.979
Preoperative CEA level (elevated versus normal)	1.309 (0.847,2.025)	0.226
SII (high versus low)	2.408 (1.522,3.808)	<0.001	1.946 (1.221,3.102)	0.005
Distance from the anal verge (≥5 cm versus < 5 cm)	0.904 (0.589,1.389)	0.646
Surgical approach (low anterior resection versus other procedures)	0.922 (0.577,1.471)	0.732
Tumour differentiation (poor + moderate versus well)	1.473 (0.874,2.483)	0.146
ypT stage (ypT3–4 versus ypT1–2)	1.636 (1.066,2.510)	0.024	NA	NA
ypN stage (ypN + versus ypN0)	2.229 (1.444,3.443)	<0.001	1.645 (1.046,2.588)	0.031
TRG (TRG 2–3 versus TRG 1)	2.696 (1.600,4.544)	<0.001	2.239 (1.320,3.797)	0.003
Adjuvant treatment (yes versus no)	0.605 (0.264,1.390)	0.236
Collagen signature	3.715 (2.745,5.029)	<0.001	2.965 (2.159,4.073)	<0.001
Overall survival
Age (years)	0.996 (0.794,1.020)	0.764
Sex (male versus female)	1.241 (0.786,1.961)	0.354
Preoperative CEA level (elevated versus normal)	1.422 (0.895,2.259)	0.136
SII (high versus low)	2.167 (1.337,3.510)	0.002	1.707 (1.043,2.795)	0.033
Distance from the anal verge (≥ 5 cm versus <5 cm)	0.927 (0.587,1.465)	0.746
Surgical approach (low anterior resection versus other procedures)	0.924 (0.561,1.522)	0.757
Tumour differentiation (poor + moderate versus well)	1.219 (0.681,2.181)	0.505
ypT stage (ypT3–4 versus ypT1–2)	1.615 (1.024,2.549)	0.039	NA	NA
ypN stage (ypN+ versus ypN0)	2.379 (1.506,3.760)	<0.001	1.659 (1.024,2.688)	0.040
TRG (TRG 2–3 versus TRG 1)	2.093 (1.241,3.530)	0.006	1.780 (1.050,3.019)	0.032
Adjuvant treatment (yes versus no)	0.720 (0.312,1.660)	0.441
Collagen signature	3.524 (2.534,4.902)	<0.001	2.852 (2.004,4.057)	<0.001

HR, hazard ratio; CEA, carcinoembryonic antigen; SII, systemic immune-inflammation index; ypT, tumour stage after neoadjuvant treatment; NA, not available; ypN, lymph node status after neoadjuvant treatment; TRG, tumour regression grade.

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