A total of 15,656 patients were included in the final analysis. Participant baseline characteristics are shown in Table 1. The mean age of this population was 57.4 (SD = 11.6). Among all patients, 24.3% had lung cancer, 17.4% had colorectal cancer, 13.8% had breast cancer (predominantly female), and 10.3% had gastric cancer. Most of the patients (65.4%) were at advanced stages of cancer (stage 3 and stage 4). The mean BMI for this population was 22.7kg/m2 (SD = 3.4) with a large variability. The mean PG-SGA score was 5.4 which fell into the category of moderately malnourished. In males, the majority (29.2%) had lung cancer, whereas among females, breast cancer cases accounted for a substantial 30.1%. Overall, gastrointestinal cancers were similarly prevalent in both males and females.
Table 1
Baseline characteristics of participants
| Overall | Male | Female | P value |
N | 15656 | 8531 | 7125 | |
Age, year | 57.4 (11.6) | 59.6 (11.2) | 54.9 (11.6) | < 0.001 |
BMI kg/m2 | 22.7 (3.4) | 22.4 (3.3) | 23.0 (3.6) | < 0.001 |
PG-SGA score | 5.4 (4.5) | 5.81 (4.6) | 4.90 (4.4) | < 0.001 |
Tumor type (%) | | | | |
Lung cancer | 3806 (24.3) | 2492 (29.2) | 1314 (18.4) | < 0.001 |
Gastric cancer | 1608 (10.3) | 1127 (13.2) | 481 (6.8) | |
Breast cancer | 2159 (13.8) | 16 (0.2) | 2143 (30.1) | |
Colorectal cancer | 2718 (17.4) | 1619 (19.0) | 1099 (15.4) | |
Others | 5365 (34.3) | 3277 (38.4) | 2088 (29.3) | |
TNM stage | | | | |
1 | 1607 (10.3) | 595 (7.0) | 1012 (14.2) | < 0.001 |
2 | 3140 (22.9) | 1466 (17.2) | 1674 (23.5) | |
3 | 3708 (27.0) | 2164 (25.4) | 1544 (21.7) | |
4 | 5268 (38.4) | 3137 (36.8) | 2131 (29.9) | |
Unknown | 1933 (12.3) | 1169 (13.7) | 764 (10.7) | |
Blood biomarkers (N = participants with complete data) |
TP, g/L | 68.6 (6.1), N = 15056 | 68.0 (6.2) | 69.3 (6.0) | < 0.001 |
Alb, g/dL | 39.6(4.4), N = 15065 | 39.1 (4.4) | 40.2 (4.31) | < 0.001 |
Crea, mmol/L | 68.3 (15.6), N = 15262 | 75.3 (14.6) | 60.0 (12.3) | < 0.001 |
TC, mmol/L | 4.7 (1.0), N = 8656 | 4.5 (0.9) | 4.8 (1.0) | < 0.001 |
Hb, g/L | 125.4 (18.1), N = 15568 | 129.4 (18.6) | 120.5 (16.4) | < 0.001 |
WBC, *10^9/L | 6.3 (2.2), N = 15579 | 6.6 (2.3) | 6.1 (2.2) | < 0.001 |
NLR | 3.1 (2.3), N = 15480 | 3.3 (2.3) | 2.9 (2.1) | < 0.001 |
Values are mean (standard deviation) or n (%). TNM, tumor, node and metastasis; BMI, body mass index; PG-SGA, patient generated-subjective global assessment; TP, total protein; Alb, albumin; Crea, creatinine; TC, total cholesterol; Hb, hemoglobin; WBC, white blood cell; NLR, neutrophils/lymphocytes ratio. |
Figure 1 shows the smoothing plots depicting the association between age and BMI in both sexes combined, and by sex, stratified by tumor types: lung cancer, gastric cancer, breast cancer, colorectal cancers and others. In general, the relationship between age and BMI exhibited a bell-shaped pattern. Notably, around the age of 40, women exhibited higher BMIs than men. Among male patients, those with lung cancer tended to have higher BMIs compared to those with gastric and colorectal cancer. In contrast, among female patients, those diagnosed with breast cancer displayed the highest BMIs, while gastric cancer patients tended to have the lowest BMIs.
Figure 2 illustrates a positive correlation between age and PG-SGA scores. This trend was evident in both males and females. Notably, among all cancer types examined, gastric cancer patients exhibited the highest PG-SGA scores, followed by colorectal and lung cancer patients. Conversely, breast cancer patients consistently had the lowest PG-SGA scores across all age groups.
Figure 3 depicts the relationships between age and the seven biomarkers in the overall population. All of the biomarkers displayed a statistically significant association with age at enrollment (Supplemental Table 1). Both albumin and total protein levels exhibited a negative correlation with age. Conversely, creatinine and the NLR demonstrated an opposing trend, increasing as age advanced. In contrast, total cholesterol and WBC counts remained relatively stable with age. Interestingly, a noticeable decline in hemoglobin levels was observed around the age of 60.
Figure 4 shows the relationship between age and the biomarkers stratified by sex. Notably, women tended to exhibit slightly higher levels of albumin, cholesterol, and total protein in comparison to men. Conversely, men tended to display higher concentrations of creatinine and hemoglobin and higher NLR and WBC counts.
However, when examining age-related changes, some intriguing patterns emerged. In women, total protein levels remained relatively consistent throughout most of the younger age groupings but started declining around the age of 60. Conversely, WBC counts in women exhibited an upward trajectory around the age of 60. Hemoglobin levels in women remained relatively constant with age, but showed a declining trend in men.
Total cholesterol increased with age in women until approximately the age of 60, while it remained relatively stable in men. Creatinine levels, on the other hand, showed an age-related increase in women but remained steady in men. Of note, men tended to have higher creatinine levels compared to women.
Figure 5 shows the relationship between age and biomarkers in males stratified by tumor type. As age increased, the levels of albumin, total protein, and hemoglobin consistently decreased in males across all included tumor types, with gastric cancer patients exhibiting the lowest concentrations. Conversely, the NLR appeared to exhibit a positive association with age across all tumor types.
Furthermore, for lung cancer and colorectal cancer patients, creatinine levels showed an increasing trend beginning at the age of 60, whereas they remained relatively stable in gastric cancer patients. WBC counts generally remained steady with advancing age, with lung cancer patients showing slightly elevated levels compared to patients of other tumor types.
As shown in Fig. 6, a distinct pattern of biomarker changes with advancing age across different cancer types was revealed for females. Albumin levels exhibited a consistent downward trend with increasing age, with breast cancer patients presenting the highest levels and gastric cancer patients the lowest. Notably, for gastric cancer patients, albumin levels started declining around the age of 40. Creatinine levels in female patients demonstrated a discernible positive correlation with age, irrespective of cancer type. For gastric cancer patients, the NLR began to increase at the age of 50, while colorectal cancer patients consistently exhibited an upward trend. Total protein levels declined in both female gastric cancer and colorectal cancer patients, commencing around the age of 50, with gastric cancer patients having lower average total protein levels compared to patients with other tumor types. In contrast, total protein levels in breast cancer patients did not display significant age-related changes.
Except for female gastric cancer patients whose cholesterol levels remained relatively stable with age, cholesterol levels in all other tumor patients generally increased as age advanced. Among female cancer patients, WBC count levels did not vary significantly with age, with lung cancer patients having slightly higher WBC counts than patients with other tumor types. Hemoglobin levels exhibited distinct trends: breast cancer patients showed an upward trend, while lung cancer patients experienced a decline around the age of 60. Notably, hemoglobin levels in female gastric cancer patients remained relatively stable before the age of 50, but a declining trend became apparent after the age of 50, with overall levels being relatively low.