Dolu S, Cengiz MB, Döngelli H, Gürbüz M, Arayici ME. Importance of hematological and inflammatory markers in the localization of gastric cancer. World J Gastrointest Oncol 2025; 17(4): 104455 [DOI: 10.4251/wjgo.v17.i4.104455]
Corresponding Author of This Article
Süleyman Dolu, Department of Gastroenterology, Faculty of Medicine, Dokuz Eylul University, İnciraltı Mahallesi Mithatpaşa cad. no:1606 Balçova/İzmir, İzmir 35340, Türkiye. suleyman.dolu@deu.edu.tr
Research Domain of This Article
Oncology
Article-Type of This Article
Retrospective Cohort Study
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Author contributions: Dolu S designed the study, acquired funding and wrote the original draft; Dolu S, Gürbüz M, and Cengiz MB were responsible for developing the methodology; Döngelli H and Arayici ME participated in the formal analysis and investigation; Dolu S, Cengiz MB, Döngelli H, Gürbüz M, and Arayici ME participated in the review and editing.
Institutional review board statement: This study was approved by the Ağrı Training and Research Hospital Scientific Research Ethics Committee (No. E-95531838-050.99-86900) and conducted in accordance with the Declaration of Helsinki.
Informed consent statement: Signed informed consent was obtained from all participants.
Conflict-of-interest statement: The authors declare that they have no conflict of interest.
STROBE statement: The authors have read the STROBE Statement—a checklist of items, and the manuscript was prepared and revised according to the STROBE Statement-a checklist of items.
Data sharing statement: No additional data are available.
Open Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Süleyman Dolu, Department of Gastroenterology, Faculty of Medicine, Dokuz Eylul University, İnciraltı Mahallesi Mithatpaşa cad. no:1606 Balçova/İzmir, İzmir 35340, Türkiye. suleyman.dolu@deu.edu.tr
Received: December 25, 2024 Revised: January 20, 2025 Accepted: February 7, 2025 Published online: April 15, 2025 Processing time: 94 Days and 23.3 Hours
Abstract
BACKGROUND
Gastric cancer is a major global health concern, often diagnosed at advanced stages, leading to poor prognosis. Proximal and distal gastric cancers exhibit distinct clinicopathological features.
AIM
To investigate the diagnostic value of hematological and inflammatory markers in differentiating proximal and distal gastric cancers and to evaluate their association with clinical outcomes.
METHODS
A retrospective cohort study was conducted on 150 patients diagnosed with gastric adenocarcinoma through histopathological analysis. Patients were categorized into proximal gastric cancer and distal gastric cancer groups. Laboratory parameters were analyzed.
RESULTS
Of the 150 patients, 84 had proximal gastric cancer and 66 had distal gastric cancer. Dysphagia was significantly more common in the proximal gastric cancer group, while anemia and higher platelet-to-lymphocyte ratio values were observed in the distal gastric cancer group (P = 0.031). Tumor stage and neutrophil-to-lymphocyte ratio emerged as independent predictors of all-cause mortality. No significant differences were found in other laboratory or biochemical parameters between the groups.
CONCLUSION
Proximal and distal gastric cancers demonstrate distinct clinical and laboratory profiles. The platelet-to-lymphocyte ratio may serve as a valuable marker in differentiating cancer localization, while the neutrophil-to-lymphocyte ratio is a prognostic indicator for mortality. These findings highlight the potential of hematological markers in optimizing diagnosis and treatment strategies for gastric cancer.
Core Tip: This study highlights the distinct clinical and laboratory profiles of proximal and distal gastric cancers. The platelet-to-lymphocyte ratio was identified as a significant marker for differentiating cancer localization, while the neutrophil-to-lymphocyte ratio emerged as an independent predictor of all-cause mortality. These findings emphasize the potential of hematological and inflammatory markers in improving diagnostic precision and guiding personalized treatment strategies for gastric cancer.
Citation: Dolu S, Cengiz MB, Döngelli H, Gürbüz M, Arayici ME. Importance of hematological and inflammatory markers in the localization of gastric cancer. World J Gastrointest Oncol 2025; 17(4): 104455
Cancer remains among the leading global causes of morbidity and mortality, with gastric cancer and other malignancies posing distinct diagnostic and therapeutic challenges[1-4]. Gastric cancer is a major contributor to cancer cases and related fatalities and is commonly diagnosed at an advanced stage[5]. Despite advancements in treatment, early detection is still difficult, which contributes to the poor prognosis. The clinical presentation varies depending on the location of the gastric cancer[6]. Proximal gastric cancer (PGC) and distal gastric cancer (DGC) are the two forms of gastric cancer that have been identified based on the cancer site[7]. Previous studies have shown that PGC differs from DGC in terms of clinicopathological characteristics[8-10]. According to the National Cancer Database from China, DGC is associated with older patients, more advanced tumor stage, and a higher prevalence of poorly differentiated tumors compared to PGC[11].
Some peripheral blood-based tests are used as indicators of systemic inflammation and are frequently linked to tumor development and metastasis[12]. The neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) are among the most well studied markers, and they are prognostic factors in various malignancies[13,14]. Of note, NLR and PLR have advantages over other inflammatory markers, including their established utility, accessibility, and cost-effectiveness. These markers are derived from routine complete blood count tests, making them readily available in clinical practice without additional costs or specialized assays. Unlike some novel markers that may require advanced laboratory techniques, NLR and PLR offer practical advantages for widespread implementation, particularly in resource-limited settings. Furthermore, in the literature, these parameters have been used not only for prognosis but also for the diagnosis and localization of malignancy. For example, Fang et al[15] demonstrated that inflammatory markers possess considerable diagnostic significance for the early identification of gastric cancer, outperforming traditional tumor markers in sensitivity[15]. Alizamir et al[16] established that the preoperative inflammatory parameters are predictive of the severity of breast masses, highlighting their critical roles in both diagnosis and prognosis. In a study from Turkey, the authors investigated the relationship between NLR and the localization of colon cancer[17].
We aimed to elucidate the diagnostic importance of inflammatory and hematological indicators in differentiating between PGCs and DGCs. We also explored the relationship between these markers and clinical attributes of gastric cancer.
MATERIALS AND METHODS
Patient characteristics
A comprehensive screening was conducted on 8900 patients who underwent esophagogastroduodenoscopy at the Ağrı Training and Research Hospital Gastroenterology Endoscopy Unit between May 2022 and December 2023. This retrospective cohort study included 150 patients histopathologically diagnosed with gastric adenocarcinoma. A histopathological diagnosis was established using tissue samples obtained during esophagogastroduodenoscopy. Patients were included if they had histopathologically confirmed gastric adenocarcinoma, comprehensive clinical and laboratory data, and sufficient follow-up information. Patients with prior malignancies, concurrent systemic infections, cirrhosis, or severe cardiovascular diseases were excluded from the study. Additionally, individuals who had recently received antiplatelet agent therapy, were on steroid use at the time of admission, had recurrent gastric cancer, or were diagnosed with hematological malignancies were excluded. The flow chart illustrating the patient inclusion process is summarized in Figure 1.
Figure 1 Flowchart illustrating the patients selecting process of the study.
Patient demographic data, clinical presentations, comorbidities, and laboratory results were retrieved from electronic health record data. Tumor characteristics, including stage, localization, and metastatic status, were determined based on imaging and pathology reports. Tumor localization (proximal or distal) was confirmed via endoscopic imaging, and an official stage classification system was used to stage the patients[18]. Accordingly, gastric cancer patients were categorized into two groups based on the localization of cancer: PGC and DGC[19]. Patients with diffuse gastric cancer involvement at the time of diagnosis were excluded from this study.
Laboratory parameters analyzed included hemoglobin concentration, white blood cell count, neutrophil count, lymphocyte count, platelet count, red cell distribution width, mean platelet volume, C-reactive protein concentration, and albumin concentration. In addition, inflammatory indices such as NLR, PLR, lymphocyte-to-monocyte ratio (LMR), and systemic immune-inflammation index (SII) were analyzed. NLR was calculated by dividing the absolute count of neutrophils by the absolute count of lymphocytes. The PLR was determined by dividing the platelet count by the lymphocyte count. The LMR was established through the division of the lymphocyte count by the monocyte count. The SII was computed with the formula (platelet count × neutrophil count)/lymphocyte count. All values are expressed as absolute counts, and calculations were performed using data from pre-diagnostic blood samples.
Outcome measures
The primary objective was to compare clinical, laboratory, and pathological characteristics between PGC and DGC groups. Assessing the predictive importance of inflammatory markers and their correlation with all-cause mortality were secondary goals.
Statistical analysis
All statistical analyses were conducted utilizing statistical product and service solutions version 24.0 (IBM Corp., Armonk, NY, United States). The normality of the data was evaluated through the Kolmogorov-Smirnov and Shapiro-Wilk tests. Continuous variables are presented as mean ± SD or median (range) and were compared using the Student’s t-test for parametric data or the Mann-Whitney U test for non-parametric data. Categorical variables were reported as frequencies (n) and percentages (%) and were analyzed using Pearson’s χ2 test or Fisher’s exact test, as appropriate. Survival analyses were executed using Kaplan-Meier curves, with group differences assessed via the log-rank test. The Cox proportional hazards regression model was employed to identify independent predictors of all-cause mortality, with results expressed as hazard ratios (HR) and 95% confidence intervals (CI). A P value < 0.05 was considered statistically significant.
RESULTS
Patient characteristics
The research encompassed a cohort of 150 individuals diagnosed with gastric adenocarcinoma, with 84 patients classified as having PGC and 66 patients classified as having DGC. (Figure 1). The cohort’s mean age was determined to be 66.4 ± 10.4 years, with no significant age disparity found between the PGC group (65.3 ± 11.0 years) and the DGC group (67.7 ± 9.5 years). Conversely, the analysis of gender distribution indicated a significant difference, as men represented a larger proportion of the cohort at 63% (P = 0.005).
Clinical presentations and comorbidities
The primary complaints at admission varied. The most frequent complaint at admission was dyspepsia, which was observed in 56% of patients diagnosed with PGC and in 67% of those diagnosed with DGC. Dysphagia solely appeared in the PGC group (P < 0.001). In contrast, anemia was more commonly found in the DGC group, affecting 24% of patients (P = 0.048).
We examined a range of comorbidities including hypertension, diabetes mellitus, cardiovascular disease, atrial fibrillation, chronic renal failure, cerebrovascular disease, and chronic respiratory disease. While the difference did not reach statistical significance (P = 0.284), the occurrence of cardiovascular disease was greater in the PGC group, with a prevalence of 24%, compared to 17% in the DGC group. The rates of diabetes mellitus and hypertension were similar between the groups (P > 0.05). Additionally, the occurrence of other conditions was low and did not reveal any significant differences between the groups.
Tumor characteristics and staging
In terms of tumor staging, most patients in both categories were found to have advanced-stage disease (stages 3 or 4). In particular, 85% of individuals in the PGC group and 77% of those in the DGC group were in these later stages. Despite these considerable values, the stage distribution did not reveal any noticeable differences between the PGC and DGC groups (P = 0.525). Metastasis was noted in 37% of the entire cohort, with similar rates observed in the PGC (40%) and DGC (36%) groups (P = 0.946).
Laboratory findings and inflammatory markers
Laboratory analyses revealed no significant differences in complete blood count and biochemical parameters between the PGC and DGC groups (P > 0.05). White blood cell count, neutrophil and lymphocyte counts, hemoglobin levels, platelet count, and other standard blood parameters were among the important indicators covered in this study. Likewise, the two groups’ levels of biochemical indicators such as albumin, liver enzymes (alanine transferase and aspartate transferase), and C-reactive protein were similar.
Notably, the PLR was significantly higher in the DGC group (191.2 ± 115.2) than in the PGC group (157.3 ± 91.5, P = 0.031). Analysis of other indices indicated no significant differences between the groups (P > 0.05).
Comparison of clinical, laboratory, and pathological features between cardia and non-cardia gastric adenocarcinomas is presented in Table 1.
Table 1 Comparison of features between cardia and non-cardia gastric adenocarcinoma, mean ± SD/n (%).
Characteristic
PGC (n = 84)
DGC (n = 66)
Total (n = 150)
P value
Age
65.3 ± 11.0
67.7 ± 9.5
66.4 ± 10.4
0.164
Gender
0.005
Female
39 (46)
16 (24)
55 (37)
Male
45 (54)
50 (76)
95 (63)
Observation duration (mo)
23.8 ± 14.4
22.7 ± 12.9
23.3 ± 13.7
0.916
Complaint at admission
Dyspepsia
47 (56)
44 (67)
91 (61)
0.182
Bleeding
19 (23)
15 (23)
34 (23)
0.987
Constitutional
7 (8)
7 (11)
14 (9)
0.935
Dysphagia
21 (25)
0 (0)
21 (14)
< 0.001
Anemia
10 (12)
16 (24)
26 (17)
0.048
Comorbidities
HT
30 (36)
22 (33)
52 (35)
0.761
DM
13 (16)
8 (12)
21 (14)
0.556
Cardiovascular
20 (24)
11 (17)
31 (21)
0.284
AF
3 (4)
0 (0)
3 (2)
0.256
CRD
10 (12)
9 (14)
19 (13)
0.752
CVD
2 (2)
4 (6)
6 (4)
0.406
CRF
3 (4)
1 (2)
4 (3)
0.631
Hypothyroidism
4 (5)
0 (0)
4 (3)
0.131
Stage
0.525
1
6 (8)
5 (9)
11 (8)
2
5 (7)
8 (14)
3 (10)
3
33 (45)
21 (36)
54 (41)
4
29 (40)
24 (41)
53 (41)
Metastasis
31 (40)
24 (36)
55 (37)
0.946
Laboratory tests
WBC, 103/UL
8.6 ± 3.3
8.1 ± 3.4
8.3 ± 3.4
0.246
Neutrophils, 103/UL
5.6 ± 2.2
5.6 ± 3.2
5.6 ± 2.7
0.473
Lym, 103/UL
2.1 ± 0.9
1.8 ± 0.7
1.9 ± 0.8
0.084
Monocytes, 103/UL
0.5 ± 0.2
0.5 ± 0.2
0.5 ± 0.2
0.454
Hemoglobin, g/dL
12.5 ± 2.7
11.9 ± 2.9
12.2 ± 2.8
0.192
RDW, %
15.2 ± 3.7
15.9 ± 3.4
15.5 ± 3.6
0.134
Platelet, 103/UL
293 ± 113
308 ± 125
299 ± 117
0.429
MPV, fL
9.5 ± 1.1
9.5 ± 1.1
9.5 ± 1.1
0.892
PDW, %
16.1 ± 0.4
15.9 ± 0.4
16.0 ± 0.4
0.623
CRP, mg/L
18.7 ± 26.8
18.1 ± 29.1
18.4 ± 27.8
0.920
Albumin, g/dL
3.8 ± 0.5
3.7 ± 5.7
3.7 ± 5.3
0.486
AST, IU/L
22.8 ± 15.2
19.6 ± 11.6
21.4 ± 13.7
0.177
ALT, IU/L
18.6 ± 15.9
17.1 ± 14.9
17.9 ± 15.5
0.539
Total bilirubin, mg/dL
0.6 ± 0.4
0.6 ± 0.5
0.6 ± 0.4
0.442
Creatinine, mg/dL
0.82 ± 0.28
0.83 ± 0.24
0.83 ± 0.26
0.589
BUN, mg/dL
40.9 ± 17.9
43.5 ± 28.5
42.1 ± 23.1
0.768
Sodium, mEq/L
138.2 ± 3.4
138.1 ± 2.9
138.1 ± 3.2
0.953
Potassium, mEq/L
4.2 ± 0.5
4.3 ± 0.5
4.2 ± 0.5
0.457
Index
NLR
2.9 ± 2.1
3.8 ± 3.7
3.3 ± 2.9
0.413
PLR
157.3 ± 91.5
191.2 ± 115.2
172.2 ± 103.6
0.031
LMR
8.8 ± 39.5
4.1 ± 2.1
6.7 ± 29.6
0.311
SII
897 ± 705
1316 ± 1856
1081 ± 1350
0.401
Death
15 (18)
12 (18)
27 (18)
0.959
Age-related differences
In this study, 150 patients were categorized into two age groups. Older patients (≥ 65 years) exhibited a greater occurrence of comorbidities, such as hypertension and cardiovascular disorders, while no notable differences were found in tumor staging or metastasis rates between the two groups. Younger patients showed higher levels of hemoglobin and albumin, whereas other laboratory results and inflammatory markers were consistent across both age groups. Mortality rates did not show any significant variation when comparing different age groups (Table 2).
Table 2 Comparison of features between elderly (> 65) and non-elderly (< 65) patients with gastric adenocarcinoma, mean ± SD/n (%).
Characteristic
Non-elderly (n = 59)
Elderly (n = 91)
Total (n = 150)
P value
Age
56.1 ± 5.9
73.1 ± 6.6
66.4 ± 10.4
< 0.001
Gender
0.571
Female
20 (34)
35 (39)
55 (37)
Male
39 (54)
56 (61)
95 (63)
Observation duration (mo)
22.1 ± 12.7
24.1 ± 14.4
23.3 ± 13.7
0.406
Complaint at admission
Dyspepsia
40 (68)
51 (56)
91 (61)
0.150
Bleeding
10 (17)
24 (26)
34 (23)
0.178
Constitutional
7 (12)
7 (8)
14 (9)
0.391
Dysphagia
8 (14)
13 (14)
21 (14)
0.900
Anemia
7 (12)
19 (21)
26 (17)
0.154
Comorbidities
HT
10 (17)
42 (46)
52 (35)
< 0.001
DM
7 (12)
14 (15)
21 (14)
0.392
Cardiovascular
7 (12)
24 (26)
31 (21)
0.032
AF
0 (0)
3 (3)
3 (2)
0.279
CRD
6 (10)
13 (14)
19 (13)
0.459
CVD
4 (2)
5 (6)
6 (4)
0.404
CRF
1 (2)
3 (3)
4 (3)
0.999
Hypothyroidism
4 (7)
0 (0)
4 (3)
0.022
Stage
0.064
1
3 (5)
8 (10)
11 (8)
2
5 (9)
8 (10)
3 (10)
3
30 (55)
24 (32)
54 (41)
4
17 (31)
36 (48)
53 (41)
Metastasis
17 (29)
38 (42)
55 (37)
0.108
Localization
0.319
Cardia
36 (61)
48 (53)
84 (56)
Non-cardia
23 (39)
43 (47)
66 (44)
Laboratory tests
WBC, 103/UL
8.3 ± 2.8
8.4 ± 3.7
8.3 ± 3.4
0.905
Neutrophils, 103/UL
5.5 ± 2.5
5.7 ± 2.8
5.6 ± 2.7
0.492
Lym, 103/UL
2.1 ± 0.8
1.9 ± 0.7
1.9 ± 0.8
0.125
Monocytes, 103/UL
0.5 ± 0.2
0.5 ± 0.1
0.5 ± 0.2
0.837
Hemoglobin, g/dL
12.8 ± 2.3
11.7 ± 2.9
12.8 ± 7.4
0.028
RDW, %
14.9 ± 2.3
15.8 ± 4.1
15.5 ± 3.6
0.101
Platelet, 103/UL
304 ± 116
295 ± 119
299 ± 117
0.662
MPV, fL
9.6 ± 1.1
9.4 ± 1.1
9.5 ± 1.1
0.386
PDW, %
16.1 ± 0.4
15.9 ± 0.4
16.0 ± 0.4
0.468
CRP, mg/L
15.9 ± 23.5
19.9 ± 30.1
18.4 ± 27.8
0.556
Albumin, g/dL
3.8 ± 0.5
3.6 ± 0.5
3.7 ± 0.5
0.014
AST, IU/L
23.8 ± 17.8
19.9 ± 10.1
21.4 ± 13.7
0.560
ALT, IU/L
22.1 ± 21.6
15.2 ± 8.9
17.9 ± 15.5
0.068
Total bilirubin, mg/dL
0.6 ± 0.4
0.6 ± 0.5
0.6 ± 0.4
0.822
Creatinine, mg/dL
0.82 ± 0.29
0.83 ± 0.25
0.83 ± 0.26
0.551
BUN, mg/dL
38.4 ± 22.3
44.4 ± 23.4
42.1 ± 23.1
0.009
Sodium, mEq/L
138.3 ± 3.1
138.1 ± 3.3
138.1 ± 3.2
0.373
Potassium, mEq/L
4.3 ± 0.4
4.2 ± 0.5
4.2 ± 0.5
0.607
Indexes
NLR
3.1 ± 2.7
3.5 ± 3.1
3.3 ± 2.9
0.133
PLR
168.4 ± 97.9
174.7 ± 107.6
172.2 ± 103.6
0.560
LMR
4.4 ± 1.8
8.3 ± 37.9
6.7 ± 29.6
0.313
SII
1023 ± 1022
1119 ± 1530
1081 ± 1350
0.294
Death
13 (22)
14 (15)
27 (18)
0.300
Cox regression analysis for all-cause mortality
Univariate Cox regression analysis identified tumor stage (HR = 2.020, 95%CI: 1.137-3.590, P = 0.017) and NLR (HR = 1.194, 95%CI: 1.086-1.313, P < 0.001) as significant predictors of all-cause mortality. Multivariate analysis confirmed stage (HR = 1.905, 95%CI: 1.039-3.492, P = 0.037) and NLR (HR = 1.205, 95%CI: 1.091-1.332, P < 0.001) as independent predictors (Table 3).
Table 3 Analysis with Cox-regression model all causes mortality.
Characteristic
Univariate
Multivariate
HR
95%CI
P value
HR
95%CI
P value
Age
1.002
0.966-1.040
0.897
1.010
0.968-1.054
0.639
Gender (female)
1.471
0.688-3.145
0.319
1.551
0.701-3.434
0.279
Cardiovascular disease
1.985
0.891-4.420
0.093
1.326
0.534-3.291
0.534
Stage (per one stage increase)
2.020
1.137-3.590
0.017
1.905
1.039-3.492
0.037
NLR
1.194
1.086-1.313
< 0.001
1.205
1.091-1.332
< 0.001
PLR
1.003
1.000-1.006
0.057
LMR
0.803
0.632-1.019
0.072
SII
1.001
1.000-1.002
< 0.001
DISCUSSION
This investigation sought to determine the relevance of inflammatory markers in establishing the localization of gastric adenocarcinoma, while also comparing the clinical attributes of gastric cancer. The results indicated that dysphagia was more prevalent in the PGC group, whereas anemia was more prevalent in the DGC group. Moreover, there was a significant increase in PLR in patients with DGC. The link between tumor location and gastric cancer prognosis is unclear. Studies suggest that PGC is associated with larger tumors and advanced stages, whereas DGC tends to manifest in older individuals and is often associated with advanced stages of the disease and poorly differentiated tumors[11,20]. This study showed that PGCs and DGCs have different clinical and inflammatory features, which can help improve their diagnosis and treatment.
Our results implied that PGC and DGC have different clinical manifestations. The physical proximity of the tumor to the esophagogastric junction, which can result in mechanical blockage, is probably why dysphagia was more common in the PGC group. Anemia, on the other hand, was more frequently seen in the DGC group, most likely as a result of ongoing blood loss linked to ulcerative lesions frequently seen in distal tumors. In a study designed in the United States, dysphagia was found to be a more common complaint in PGCs at time of diagnosis, and bleeding was observed with a similar frequency in proximal and non-PGCs[21]. Bleeding is a common symptom in ulcerative gastric cancer[22]. This study suggests that bleeding may be a universal symptom that does not depend on location. Recognizing these variations is essential for improving early detection and optimizing tumor-specific, patient-centered treatment strategies. Ultimately, this will enhance clinical results and better manage patients with gastric cancer.
The present investigation did not reveal statistically significant variations in tumor stage or metastatic rates between the two groups; however, previous studies have reported conflicting findings[20,23,24]. This discrepancy may be explained by variations in study sample numbers, demographics, staging, and diagnostic techniques. It also highlights the potential influence of regional and demographic factors on tumor biology and clinical presentation.
Regarding the anatomical distribution of gastric cancer, DGCs exhibited a notably elevated PLR. However, no notable differences were detected for the other parameters. Similarly, in a study conducted in China, the authors found that elevated PLR was significantly more common in tumors located in the lower esophagus than in those located in the middle esophagus. This study did not reveal any statistically significant difference in NLR levels between tumors located in the middle and lower esophagus[25]. The PLR has been acknowledged as a prognostic indicator in gastric cancer, extending beyond its role as a diagnostic marker[15,26]. The relationship between platelets and cancer has been previously investigated. Platelets actively contribute to the growth and spread of tumors through various mechanisms, such as transmigration of tumor cells out of the vasculature, prevention of cell-mediated immunity that eliminates malignant cells, and creation of the tumor[27-31]. The association between higher PLR and DGC observed in this study may be linked to chronic inflammation often associated with DGC, potentially driven by Helicobacter pylori infection or dietary and environmental factors that are more common in distal gastric carcinogenesis[32,33]. This study underscores the diagnostic significance of the PLR in differentiating the localization of gastric cancers. Gaining more profound insight into the mechanisms that govern this relationship could aid in the creation of innovative therapeutic strategies. Conversely, the NLR, LMR, and SII were not significantly different between the PGC and DGC groups. This implies that these markers may not be enough to detect the distinct anatomical differences in gastric cancer.
In this investigation, tumor stage and NLR were recognized as significant independent predictors of all-cause mortality, as demonstrated by the results of both univariate and multivariate Cox regression analyses. According to previous studies, poor prognosis and distant metastases are linked to an elevated NLR in gastric cancer[34,35]. Although NLR was not a guide in distinguishing PGC from DGC in our study, it was associated with poor prognosis, supporting other studies.
As emphasized in prior studies, the quality of nucleic acids extracted from biological samples is a critical determinant of the reliability of genomic and transcriptomic analyses[36]. In the context of inflammatory marker analysis, the preservation methods employed for tumor samples play a pivotal role in maintaining molecular integrity[37-40]. Suboptimal preservation conditions can lead to RNA degradation, altered expression profiles, and potential biases in the quantification of inflammatory markers. Consequently, standardizing preservation protocols and evaluating their impact on specific biomarkers, particularly those linked to inflammation in tumor microenvironments, are essential steps to enhance the reproducibility and validity of genomic studies in oncology.
PLR and NLR are simple and cost-effective biomarkers widely used to evaluate systemic inflammation. In conditions such as gastric cancer, where inflammation plays a crucial role, these markers have shown significant potential for prognostication and treatment monitoring[15,41]. Elevated PLR and NLR levels have been associated with poor outcomes and advanced disease stages. However, further studies are required to establish standardized cutoff values and validate their predictive utility across diverse populations before integration into routine clinical practice[41,42]. Nevertheless, integrating these markers into standard oncology workflows requires robust evidence from large, prospective studies that address potential confounding variables, such as concurrent infections or comorbidities. Moreover, the establishment of personalized cutoff thresholds that account for factors like age, tumor biology, and treatment modalities could further refine the predictive accuracy of PLR and NLR. Ultimately, combining these inflammatory markers with emerging molecular and genetic analyses may provide a more comprehensive approach to risk stratification and therapeutic monitoring in gastric cancer.
This study also had several limitations. First, our study is a single-center and retrospective study. Second, we could not evaluate the tumor subgroups in this study. Third, the exclusion of patients with systemic diseases and prior malignancies limits the generalizability of the findings, and may affect the applicability of the results. Future studies should validate these findings in larger prospective cohorts and explore molecular and genomic data to enhance the diagnostic accuracy.
CONCLUSION
In conclusion, PGC has different clinical presentations and laboratory behaviors than DGC. Dysphagia is more common in PGC, whereas bleeding is frequently observed in DGC. The PLR is significantly higher in patients with DGC. Elevated PLR may offer valuable insights into the role of systemic inflammation in gastric cancer location. Therefore, the PLR can be included in clinical evaluation and effective treatment regimens.
ACKNOWLEDGEMENTS
We would like to express our gratitude to all of the patients who participated in this study for their patience and encouragement.
Footnotes
Provenance and peer review: Unsolicited article; Externally peer reviewed.
Peer-review model: Single blind
Specialty type: Oncology
Country of origin: Türkiye
Peer-review report’s classification
Scientific Quality: Grade A
Novelty: Grade B
Creativity or Innovation: Grade B
Scientific Significance: Grade A
P-Reviewer: Okubo Y S-Editor: Fan M L-Editor: Filipodia P-Editor: Zhang XD
Sung H, Jiang C, Bandi P, Minihan A, Fidler-Benaoudia M, Islami F, Siegel RL, Jemal A. Differences in cancer rates among adults born between 1920 and 1990 in the USA: an analysis of population-based cancer registry data.Lancet Public Health. 2024;9:e583-e593.
[PubMed] [DOI][Cited in This Article: ][Reference Citation Analysis (0)]
Arayici ME, Basbinar Y, Ellidokuz H. The impact of cancer on the severity of disease in patients affected with COVID-19: an umbrella review and meta-meta-analysis of systematic reviews and meta-analyses involving 1,064,476 participants.Clin Exp Med. 2023;23:2221-2229.
[PubMed] [DOI][Cited in This Article: ][Cited by in Crossref: 5][Reference Citation Analysis (0)]
Arayici ME, Kipcak N, Kayacik U, Kelbat C, Keskin D, Kilicarslan ME, Kilinc AV, Kirgoz S, Kirilmaz A, Kizilkaya MA, Kizmaz IG, Kocak EB, Kochan E, Kocpinar B, Kordon F, Kurt B, Ellidokuz H. Effects of SARS-CoV-2 infections in patients with cancer on mortality, ICU admission and incidence: a systematic review with meta-analysis involving 709,908 participants and 31,732 cancer patients.J Cancer Res Clin Oncol. 2023;149:2915-2928.
[PubMed] [DOI][Cited in This Article: ][Cited by in Crossref: 1][Cited by in RCA: 9][Article Influence: 3.0][Reference Citation Analysis (0)]
Mithany RH, Shahid MH, Manasseh M, Saeed MT, Aslam S, Mohamed MS, Daniel N. Gastric Cancer: A Comprehensive Literature Review.Cureus. 2024;16:e55902.
[PubMed] [DOI][Cited in This Article: ][Reference Citation Analysis (0)]
Zhao L, Huang H, Zhao D, Wang C, Tian Y, Yuan X, Ma F, Ren H, Zhao Y, Aimaiti S, Zhang S, Zhou H, Wang T, Wang N, Sun Y, Bai X, Chen Y. Clinicopathological Characteristics and Prognosis of Proximal and Distal Gastric Cancer during 1997-2017 in China National Cancer Center.J Oncol. 2019;2019:9784039.
[PubMed] [DOI][Cited in This Article: ][Cited by in Crossref: 11][Cited by in RCA: 15][Article Influence: 2.5][Reference Citation Analysis (0)]
Maehara Y, Moriguchi S, Kakeji Y, Orita H, Haraguchi M, Korenaga D, Sugimachi K. Prognostic factors in adenocarcinoma in the upper one-third of the stomach.Surg Gynecol Obstet. 1991;173:223-226.
[PubMed] [DOI][Cited in This Article: ]
Wang X, Liu F, Li Y, Tang S, Zhang Y, Chen Y, Khan SA. Comparison on Clinicopathological Features, Treatments and Prognosis between Proximal Gastric Cancer and Distal Gastric Cancer: A National Cancer Data Base Analysis.J Cancer. 2019;10:3145-3153.
[PubMed] [DOI][Cited in This Article: ][Cited by in Crossref: 12][Cited by in RCA: 25][Article Influence: 4.2][Reference Citation Analysis (0)]
Jarmuzek P, Kozlowska K, Defort P, Kot M, Zembron-Lacny A. Prognostic Values of Systemic Inflammatory Immunological Markers in Glioblastoma: A Systematic Review and Meta-Analysis.Cancers (Basel). 2023;15.
[PubMed] [DOI][Cited in This Article: ][Cited by in RCA: 35][Reference Citation Analysis (0)]
Salciccia S, Frisenda M, Bevilacqua G, Viscuso P, Casale P, De Berardinis E, Di Pierro GB, Cattarino S, Giorgino G, Rosati D, Del Giudice F, Sciarra A, Mariotti G, Gentilucci A. Prognostic role of platelet-to-lymphocyte ratio and neutrophil-to-lymphocyte ratio in patients with non-metastatic and metastatic prostate cancer: A meta-analysis and systematic review.Asian J Urol. 2024;11:191-207.
[PubMed] [DOI][Cited in This Article: ][Cited by in Crossref: 1][Reference Citation Analysis (0)]
Fang T, Wang Y, Yin X, Zhai Z, Zhang Y, Yang Y, You Q, Li Z, Ma Y, Li C, Song H, Shi H, Zhang Y, Yu X, Gao H, Sun Y, Xie R, Xue Y. Diagnostic Sensitivity of NLR and PLR in Early Diagnosis of Gastric Cancer.J Immunol Res. 2020;2020:9146042.
[PubMed] [DOI][Cited in This Article: ][Cited by in Crossref: 30][Cited by in RCA: 91][Article Influence: 18.2][Reference Citation Analysis (0)]
Alizamir A, Dehghan Azad S, Pirdehghan A, Moradi A. Preoperative Neutrophil: Lymphocyte Ratio, Platelet: Lymphocyte Ratio, and C-Reactive Protein Levels Predictive Value in Determining the Severity of Breast Mass.Iran J Pathol. 2022;17:413-418.
[PubMed] [DOI][Cited in This Article: ][Cited by in Crossref: 3][Cited by in RCA: 3][Article Influence: 1.0][Reference Citation Analysis (0)]
Türker S, Karaçin C, İmamoğlu Gİ, Eren T, Esen R, Çılbır E, Altınbaş M, Aydın İsak Ö, Yazılıtaş D. The relationship between localization and neutrophil lymphocyte ratio in colon carcinoma.Ortadogu Tıp Derg. 2018;10:64-67.
[PubMed] [DOI][Cited in This Article: ]
Amin MB, Greene FL, Edge SB, Compton CC, Gershenwald JE, Brookland RK, Meyer L, Gress DM, Byrd DR, Winchester DP. The Eighth Edition AJCC Cancer Staging Manual: Continuing to build a bridge from a population-based to a more "personalized" approach to cancer staging.CA Cancer J Clin. 2017;67:93-99.
[PubMed] [DOI][Cited in This Article: ][Cited by in Crossref: 2341][Cited by in RCA: 4073][Article Influence: 509.1][Reference Citation Analysis (4)]
Petrelli F, Ghidini M, Barni S, Steccanella F, Sgroi G, Passalacqua R, Tomasello G. Prognostic Role of Primary Tumor Location in Non-Metastatic Gastric Cancer: A Systematic Review and Meta-Analysis of 50 Studies.Ann Surg Oncol. 2017;24:2655-2668.
[PubMed] [DOI][Cited in This Article: ][Cited by in Crossref: 44][Cited by in RCA: 45][Article Influence: 5.6][Reference Citation Analysis (0)]
Huang Q, Shi J, Sun Q, Gold JS, Chen J, Wu H, Yu H, Zhang Y, Mashimo H, Yu C, Manasco T, Guan W, Lauwers GY. Clinicopathological characterisation of small (2 cm or less) proximal and distal gastric carcinomas in a Chinese population.Pathology. 2015;47:526-532.
[PubMed] [DOI][Cited in This Article: ][Cited by in Crossref: 22][Cited by in RCA: 19][Article Influence: 2.1][Reference Citation Analysis (0)]
Gou M, Zhang Y. Pretreatment platelet-to-lymphocyte ratio (PLR) as a prognosticating indicator for gastric cancer patients receiving immunotherapy.Discov Oncol. 2022;13:118.
[PubMed] [DOI][Cited in This Article: ][Cited by in Crossref: 5][Reference Citation Analysis (0)]
Liao K, Zhang X, Liu J, Teng F, He Y, Cheng J, Yang Q, Zhang W, Xie Y, Guo D, Cao G, Xu Y, Huang B, Wang X. The role of platelets in the regulation of tumor growth and metastasis: the mechanisms and targeted therapy.MedComm (2020). 2023;4:e350.
[PubMed] [DOI][Cited in This Article: ][Cited by in Crossref: 5][Cited by in RCA: 6][Article Influence: 3.0][Reference Citation Analysis (0)]
Palumbo JS, Talmage KE, Massari JV, La Jeunesse CM, Flick MJ, Kombrinck KW, Jirousková M, Degen JL. Platelets and fibrin(ogen) increase metastatic potential by impeding natural killer cell-mediated elimination of tumor cells.Blood. 2005;105:178-185.
[PubMed] [DOI][Cited in This Article: ][Cited by in Crossref: 646][Cited by in RCA: 727][Article Influence: 34.6][Reference Citation Analysis (0)]
Morgan AD, Seely KD, Hagenstein LD, Florey GM, Small JM. Bacterial Involvement in Progression and Metastasis of Adenocarcinoma of the Stomach.Cancers (Basel). 2022;14.
[PubMed] [DOI][Cited in This Article: ][Reference Citation Analysis (0)]
Wang H, Ding Y, Li N, Wu L, Gao Y, Xiao C, Jiang H, Zheng Y, Mao C, Deng J, Wang H, Xu N. Prognostic Value of Neutrophil-Lymphocyte Ratio, Platelet-Lymphocyte Ratio, and Combined Neutrophil-Lymphocyte Ratio and Platelet-Lymphocyte Ratio in Stage IV Advanced Gastric Cancer.Front Oncol. 2020;10:841.
[PubMed] [DOI][Cited in This Article: ][Cited by in Crossref: 22][Cited by in RCA: 38][Article Influence: 7.6][Reference Citation Analysis (0)]
Okubo Y, Toyama N, Kasajima R, Toda S, Hayashi H, Yoshioka E, Washimi K, Sato S, Hiroshima Y, Hasegawa C, Yuguchi S, Kadoya M, Narimatsu H, Masudo K, Iwasaki H, Yokose T, Miyagi Y. Effective Preparation of FFPE Tissue Samples for Preserving Appropriate Nucleic Acid Quality for Genomic Analysis in Thyroid Carcinoma.Endocr Pathol. 2024;35:372-384.
[PubMed] [DOI][Cited in This Article: ][Reference Citation Analysis (0)]
Arayici ME, İnal A, Basbinar Y, Olgun N. Evaluation of the diagnostic and prognostic clinical values of circulating tumor DNA and cell-free DNA in pancreatic malignancies: a comprehensive meta-analysis.Front Oncol. 2024;14:1382369.
[PubMed] [DOI][Cited in This Article: ][Reference Citation Analysis (0)]
