Zhang KN, Jin ML, Zhai ZW. Relationship between prognosis and glucose transporter-1 and Ki-67 expression in obstructive colon cancer pre and post stent placement. World J Gastrointest Surg 2025; 17(6): 104505 [DOI: 10.4240/wjgs.v17.i6.104505]
Corresponding Author of This Article
Zhi-Wei Zhai, Department of General Surgery, Beijing Chao-Yang Hospital, Capital Medical University, No. 8 Gongren Tiyuchang Nanlu, Chaoyang District, Beijing 100020, China. zhiweizhai@ccmu.edu.cn
Research Domain of This Article
Pathology
Article-Type of This Article
Retrospective 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/
Co-corresponding authors: Mu-Lan Jin and Zhi-Wei Zhai.
Author contributions: Jin ML and Zhai ZW contributed equally to the study and as co- corresponding authors of this manuscript; Zhang KN contributed to original draft preparation, writing, and review; Jin ML contributed to conceptualization, supervision, and immunohistochemical analyses; Zhai ZW contributed to conceptualization, supervision, and statistical analysis; and all authors have read and agreed to the published version of the manuscript. In this study, stent implantation and surgical treatment were performed in the Department of General Surgery, whereas tumor pathological diagnosis and immunohistochemical analysis were conducted in the Department of Pathology. This research required collaborative efforts between the two departments to be completed successfully; neither department could have accomplished it independently. Zhai ZW and Jin ML jointly designed the study, analyzed the research results, and provided supervision and management throughout the entire process to ensure its smooth progression. Zhai ZW and Jin ML are jointly responsibility for the authenticity of the research findings and declare that there is no conflict of interest. Given their equal contributions to this work, they should be recognized as co-corresponding authors.
Institutional review board statement: This study was approved by the Ethics Committee of Beijing Chaoyang Hospital, Capital Medical University (2016-ke-161).
Informed consent statement: Informed consent was obtained from all patients before treatment.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Data sharing statement: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: Zhi-Wei Zhai, Department of General Surgery, Beijing Chao-Yang Hospital, Capital Medical University, No. 8 Gongren Tiyuchang Nanlu, Chaoyang District, Beijing 100020, China. zhiweizhai@ccmu.edu.cn
Received: December 27, 2024 Revised: April 21, 2025 Accepted: May 14, 2025 Published online: June 27, 2025 Processing time: 154 Days and 21.7 Hours
Abstract
BACKGROUND
Self-expandable metallic stent (SEMS) placement is a common intervention for obstructive left-sided colon cancer. However, the long-term prognosis post-SEMS placement remains debated. Mechanical compression within the tumor caused by SEMS may induce vascular compression, leading to tissue ischemia and hypoxia. These alterations in the tumor microenvironment could affect patient prognosis.
AIM
To assess the influence of glucose transporter-1 (GLUT-1) and Ki-67 expression in obstructive colon cancer tissues pre and post SEMS placement on patient prognosis.
METHODS
A retrospective analysis was conducted on clinical and pathological data from 71 patients with obstructive colon cancer who underwent SEMS placement followed by surgery. Paired colon cancer tissue samples were collected from each patient pre and post SEMS placement. Immunohistochemical techniques were employed to evaluate GLUT-1 and Ki-67 expression in the specimens.
RESULTS
The high expression rates of GLUT-1 in the samples obtained before and after SEMS placement were 14.1% and 43.7%, respectively (P < 0.001). GLUT-1 expression was associated with vascular invasion post-SEMS placement (P = 0.03). Ki-67 expression showed no significant difference pre and post SEMS placement and was unrelated to clinical pathological characteristics (all P > 0.05). The high expression rates of GLUT-1 in the samples obtained before and after SEMS placement were associated with worse recurrence-free interval (pre-SEMS: 40.0% vs 72.3%, P = 0.026; post-SEMS: 45.5% vs 85.7%, P = 0.001). Cox regression analysis revealed that both pre-SEMS placement (HR = 3.490, 95%CI: 1.165-10.453, P = 0.026) and post-SEMS placement (HR = 4.335, 95%CI: 1.539-12.214, P = 0.006) GLUT-1 expression were adverse prognostic factors for patients.
CONCLUSION
Though the precise impact of stent placement on the mechanical compression and biological behavior of tumors is not fully understood, our study found an increase in GLUT-1 expression in tumor tissues after SEMS placement. Tumor GLUT-1 serves as a prognostic biomarker for the survival of patients with obstructive colon cancer treated with SEMS placement.
Core Tip: Self-expanding metallic stent placement is becoming a more common treatment approach for obstructive left-sided colon cancer, there is still ongoing debate regarding its long-term impact on patient prognosis. Stent expansion can result in the compression of blood vessels within the tumor due to mechanical pressure, may induce changes in the tumor microenvironment, potentially affecting patient prognosis. Our study found an increase in glucose transporter-1 (GLUT-1) expression in tumor tissues after self-expanding metallic stent placement. Tumor GLUT-1 serves as a prognostic biomarker for the survival of patients with obstructive colon cancer treated with self-expanding metallic stent placement.
Citation: Zhang KN, Jin ML, Zhai ZW. Relationship between prognosis and glucose transporter-1 and Ki-67 expression in obstructive colon cancer pre and post stent placement. World J Gastrointest Surg 2025; 17(6): 104505
Colorectal cancer (CRC) currently ranks third in terms of incidence and second in terms of mortality worldwide[1]. Approximately 20% of patients with CRC present with intestinal obstruction at the time of diagnosis, with 70% of these obstructions occurring in the left half of the colon[2]. Failure to promptly and effectively relieve the obstruction can lead to severe complications such as electrolyte imbalance, intestinal wall ischemic necrosis, perforation, infectious shock, and a potential threat to life. Therefore, once diagnosed, appropriate measures should be taken promptly for treatment. Acute large bowel obstruction is one of the most common reasons for emergency surgery in CRC. However, the incidence of complications and mortality associated with emergency surgery is significantly higher than that of elective surgery[3].
In 1991, Dohmoto et al[4] first proposed the use of self-expandable metallic stent (SEMS) as a new approach to treating malignant colorectal obstructions. Subsequently, Tejero et al[5] introduced the concept of using SEMS for the treatment of malignant intestinal obstructions followed by surgery 1-2 weeks later, effectively transitioning emergency surgery into an elective procedure. Compared to emergency surgery, SEMS placement as a transitional treatment before surgical intervention provides a window of time to improve the patient's general condition. This allows for a comprehensive evaluation of the patient's condition, thus increasing the rate of laparoscopic surgery, improving primary anastomosis rates, reducing the rate of ostomy creation, decreasing the incidence of wound infections, and simultaneously reducing surgical mortality rates[6-8].
Although SEMS placement is becoming a more common treatment approach for obstructive left-sided colon cancer, there is still ongoing debate regarding its long-term impact on patient prognosis[9]. A meta-analysis by Foo et al[10] found that, compared to emergency surgery, patients who underwent SEMS placement had poorer overall survival and higher rates of local recurrence. However, recent reports have indicated that there may be no significant difference in long-term survival between patients undergoing SEMS placement and those undergoing emergency surgery[11-13]. Currently, there is a lack of reliable data from randomized controlled trials to assess this issue.
Recent studies have suggested that mechanical compression can drive malignant cells towards a more invasive phenotype[14] and promote angiogenesis[15]. Some preliminary research has examined histological changes in patients after SEMS placement[16,17]. The placement of vascular stent can result in compression of the vasa vasorum, leading to hypoxia and subsequent intimal hyperplasia[18]. Soid stress was first described by Nia et al[19] as the mechanical stress that is confined within and transmitted by the solid and elastic components of both the extracellular matrix and cells present in the tumor microenvironment. They found solid stress facilitates tumor progression and diminishes the effectiveness of anticancer therapies by compressing blood vessels and contributing to hypoxia[19].
SEMS expansion can result in the compression of blood vessels within the tumor due to mechanical pressure, leading to tissue ischemia and hypoxia. This, in turn, may induce changes in the tumor microenvironment, potentially affecting patient prognosis. Research has shown that high expression of glucose transporter-1 (GLUT-1) in tumor cells can facilitate the transfer and absorption of glucose, even in anaerobic environments, providing abundant materials for anaerobic glycolysis, thereby promoting the invasion, growth, and metastasis of tumor cells[20]. The expression of Ki-67 protein, found within the cell nucleus, serves as a typical proliferation marker, and its overexpression is considered a prognostic marker for many types of malignant tumors[21]. The objective of this retrospective study is to evaluate the impact of GLUT-1 and Ki-67 expression in tumor tissues before and after SEMS placement in obstructive colon cancer on patient prognosis.
MATERIALS AND METHODS
Patients, treatment, clinicopathologic data and follow up
A retrospective analysis was conducted on clinical and pathological data from patients with obstructive colon cancer underwent SEMS placement followed by surgery at Beijing Chaoyang Hospital, Capital Medical University, between 2016 and 2020. Cases were selected based on inclusion and exclusion criteria. Inclusion criteria: (1) Clinical presentation and radiological examinations confirming complete colonic obstruction; (2) Pathological confirmation of primary colonic adenocarcinoma; and (3) Exclusion of distant metastasis based on examinations such as thoracoabdominal computed tomography (CT) scans. Exclusion criteria: (1) Multiple CRCs; (2) Patients who did not undergo surgical treatment after SEMS placement; (3) Patients who developed distant metastases prior to surgery following SEMS placement; and (4) Patients with incomplete clinical and pathological data and inadequate follow-up information. This study was approved by the Ethics Committee of Beijing Chaoyang Hospital, Capital Medical University (2016-ke-161). Informed consent was obtained from all patients before treatment.
Clinically, obstruction was characterized by the inability of the intestine to pass stool and gas. The diagnosis of acute left-sided colonic obstruction relied on clinical symptoms (such as abdominal distension, pain, inability to defecate or pass gas), physical examination, abdominal X-ray, and abdominal CT scans. Upon confirmation of diagnosis during patient presentation, experienced gastroenterologists performed SEMS (WallFlex; Boston Scientific Corporation, Natick, MA, United States) placement under colonoscopy guidance and conducted tissue biopsies. Fluoroscopy and endoscopy were utilized for visualization and guidance during the insertion of SEMS. The extent and position of stent expansion were verified via abdominal CT. Technical success denoted the successful placement of the stent at the narrowed site, while clinical success signified satisfactory intestinal decompression within 24 hours of stent placement, resulting in the alleviation of obstructive symptoms in patients.
Following SEMS placement, surgical treatment was performed 2-4 weeks later. The choice between laparoscopic or open surgery was determined by the surgeon's discretion and the patient's clinical condition. Patients discovered to have abdominal metastasis during intraoperative exploration were excluded from this study. Subsequent to surgery, all patients underwent 6 months of chemotherapy following the CAPOX regimen: Oxaliplatin at 130 mg/m2 administered intravenously on day 1, followed by Capecitabine at 1000 mg/m2 orally twice daily from days 1 to 14, with a 3-week cycle.
During our study, 75 patients with acute obstructing colon cancer underwent SEMS placement in our department. Four patients were excluded from this analysis: Two patients (2.7%) due to technical failure (inability to pass a guidewire), one patient (1.3%) due to perforation, and one patient (1.3%) due to metastasis before the operation. The patient with metastasis received chemotherapy without undergoing surgery, while emergency surgery was performed on the other three patients. Ultimately, A total of 71 cases were included in this study following the selection process. General clinical data such as age, gender, and tumor location, along with pathological data including differentiation type, depth of tumor invasion, lymph node involvement, neural invasion, vascular invasion, and p tumor node metastasis (TNM) staging (according to the 7th edition of the American Joint Committee on Cancer TNM system), were collected for each patient. Additionally, the most recent follow-up dates for the patients were recorded.
The patients were regularly checked by a colorectal surgeon every three months during the initial two years after the operation, and then every six months for the next three years. At each visit, they underwent a physical examination, a complete blood count, blood chemistry analysis, and measurement of carcinoembryonic antigen levels. Chest X-rays and abdominal CT scans were done every six months after treatment. Colonoscopy was carried out once a year following the surgery. The recurrence-free interval (RFI) is defined as the period from the date of surgery to the occurrence of the first tumor relapse, which includes local-regional recurrence or distant metastasis.
Immunohistochemistry
All 71 specimens, including paired preoperative biopsy specimens and postoperative tissue specimens, were fixed in 10% neutral formalin and embedded in paraffin. Tissue wax blocks were consecutively sectioned to a thickness of 4 μm and stained using an automated immunohistochemistry instrument (BenchMark XT, Ventana Medical Systems Inc., Tucson, AZ, United States). The following antibodies were used for immunohistochemistry: GLUT-1 [Abcam, Cambridge, United Kingdom; diluted 1: 200 in phosphate-buffered saline (PBS)] and Ki-67 (Novocastra, Newcastle, United Kingdom; diluted 1: 2000 in PBS).
Immunohistochemical analyses
Immunohistochemical staining were blindly evaluated by at least two experienced pathologists. The Cohen’s kappa coefficient between the two pathologists was 0.845 (P < 0.001), indicating strong agreement. GLUT-1 positivity was mainly observed in the cell membrane and cytoplasm. A semi-quantitative assessment was performed based on the percentage of positive cells relative to the total cell count, following the method reported by Cooper et al[22]: Scores were assigned as follows: 0 for specimens with no positive cells, 1 for 1%-10% positive cells, 2 for 10%-50% positive cells, and 3 for more than 50% positive cells. Scores of 0-2 were considered low expression, and a score of 3 was considered high expression. Ki-67 expression was assessed by counting 500-1000 tumor cells in at least three high-power fields (× 40), depending on the size of the tumor tissue. Ki-67 expression was quantified as the percentage of stained tumor cells relative to the total number of tumor cells. An expression level of < 30% was considered low, and ≥ 30% was considered high expression[23].
Statistical analysis
Statistical analysis was performed using SPSS 23.0 software (SPSS Inc., Chicago, IL, United States). Normally distributed continuous data were presented as mean ± SD, and comparisons between two groups were made using independent sample t-tests. Categorical data were expressed as counts (percentages), and comparisons between two groups were performed using χ2 tests or Fisher's exact probability test. Survival analysis was conducted using Kaplan-Meier analysis with the Log-rank test. Cox regression models were used for both univariate and multivariate analyses of prognostic factors. A P-value of < 0.05 was considered statistically significant.
RESULTS
Clinicopathologic characteristics
Patients with colonic obstruction underwent SEMS placement followed by surgery with an average interval of 2.3 ± 0.4 weeks. The patients had an average age of 64.7 ± 9.4 years (range 43-82 years), with a male-to-female ratio of 1.5, and males comprised 60% of the cohort. Tumors were located in the sigmoid colon in 48 cases (67.6%) and in the transverse colon to the descending colon in 23 cases (32.4%). Among these patients, there were no stage I cases, 25 cases were stage II (35.2%), and 46 cases were stage III (64.8%). The postoperative patients underwent a median of 3.4 ± 0.5 cycles of chemotherapy.
Changes in GLUT-1 and Ki-67 expression before and after stent placement and their relationship with clinicopathologic factors
The immunohistochemical staining results for Ki-67 and GLUT-1 are shown in Figure 1. Relationship between GLUT-1 expression and various patient characteristics is summarized in Table 1. In this study, the high expression rate of Ki-67 in tissues after SEMS placement was 66.2%, slightly higher than the 63.4% observed before SEMS placement, but this difference was not statistically significant (P > 0.05). Additionally, Ki-67 expression was not associated with other clinicopathological characteristics (all P > 0.05). GLUT-1 expression in tissues after SEMS placement showed a high expression rate of 43.7%, significantly higher than the 14.1% observed before SEMS placement, with a statistically significant difference (P < 0.001). In tissues after SEMS placement, GLUT-1 expression was correlated with vascular invasion (P = 0.03). The longer interval between SEMS placement and surgery did not associate with the increased expression (all P > 0.05).
Figure 1 Representative images of glucose transporter-1 and Ki-67 immunohistochemistry in malignant large bowel obstruction.
A and B: Low and high glucose transporter-1 within the tumor microenvironment; C and D: Low and high Ki-67 within the tumor microenvironment. (magnification: 200 ×).
Table 1 Relationship between glucose transporter-1 expression and various patient characteristics (n = 71), n (%).
Correlation of pre- and post-stent placement GLUT-1 expression with prognosis
All patients were followed up from the time of surgery, with a median follow-up time of 40.3 months (range 2-118 months). The 3-year RFI was 68.0%. There were 12 cases of liver metastasis, 3 cases of lung metastasis, 4 cases of simultaneous liver and lung metastasis, and 5 cases of abdominal metastasis. The rate of GLUT-1 overexpression was higher in patients with liver metastasis (including hepatopulmonary simultaneous metastasis) both before and after SEMS placement, compared to those with other types of metastasis (lung or abdominal), but the difference did not reach statistical significance (31.3% vs 12.5%, P = 0.319; 75.0% vs 62.5%, P = 0.428). Kaplan-Meier survival analysis revealed that higher GLUT-1 expression in tumor tissues obtained from pre-SEMS placement biopsies was associated with worse RFI (40.0% vs 72.3%, P = 0.026) (Figure 2A). Similarly, in specimens obtained after surgical resection, higher GLUT-1 expression in tumor tissues was associated with worse RFI (45.5% vs 85.7%, P = 0.001) (Figure 2B). Ki-67 expression in tumor tissues was not associated with RFI (all P > 0.05).
Figure 2 Kaplan-Meier curves of recurrence-free interval with glucose transporter-1 in malignant large bowel obstruction.
A: Kaplan-Meier curves demonstrating that tumor glucose transporter-1 (GLUT-1) expression is associated with 3-year recurrence-free interval (RFI) in pre-self-expandable metallic stent (SEMS) biopsies (P = 0.026); B: Kaplan-Meier curves demonstrating that tumor GLUT-1 expression is associated with 3-year RFI in post-SEMS surgical tissues (P = 0.001). GLUT-1: Glucose transporter-1; SEMS: Self-expandable metallic stent.
Independent prognostic factors for patients with CRC and stent placement-related bowel obstruction
The results of the univariate and multivariate analyses for 3-year RFI are presented in Table 2. The univariate analysis indicated that RFI was associated with vascular invasion (P = 0.03), neural invasion (P = 0.02), N stage (P = 0.011), TNM stage (P = 0.011), pre-SEMS GLUT-1 expression (P = 0.036), and post-SEMS GLUT-1 expression (P = 0.002). Baseline variables that showed a univariate relationship with the outcome were included in the multivariate Cox proportional hazards regression model. The Schoenfeld residual analysis was conducted for all variables in the multivariate model, confirming that the hazard ratios of the covariates remained constant over time (all P > 0.05). In the multivariate Cox regression model, high expression of pre-SEMS GLUT-1 (HR = 3.490, 95%CI: 1.165-10.453, P = 0.026) and post-SEMS GLUT-1 (HR = 4.335, 95%CI: 1.539-12.214, P = 0.006) in the tumor microenvironment were identified as adverse prognostic factors for RFI. Additionally, lymph node involvement (HR = 3.876, 95%CI: 1.018-14.684, P = 0.047) was also identified as an adverse prognostic factor for RFI.
Table 2 Univariate and multivariate analysis of cliniopathologic parameters on 3-year recurrence-free interval.
SEMS placement for obstructing colonic caner has been recommended by several bodies such as European Society of Gastrointestinal Endoscopy[24], American Gastroenterological Association[25], and World Society of Emergency Surgery[26]. The technical and clinical success rate of 75 patients in our study was found to be 97.3%, with a minimal incidence of perforation (1.3%) and metastasis (1.3%). These findings support the feasibility and safety of this approach.
Despite the widespread use of SEMS placement for the treatment of obstructive CRC, there is still no clear consensus on the changes in the tumor microenvironment and the long-term prognosis of patients after stent placement. Percutaneous transluminal angioplasty is considered the most reliable treatment for symptomatic vascular narrowing. This procedure widens the narrowed part of the artery using a catheter balloon and often includes stent placement[27]. Increased compression during stenting can lead to hypoxia in the outer wall. This effect becomes more pronounced in cases of stent overexpansion, as shown by Santilli et al[28]. Solid stress has been recognized as an important factor in tumor biology, as it contributes to tumor progression and reduces treatment effectiveness by compressing blood vessels and causing hypoxia[19]. Therefore, we suggest that the pressure from the intestinal stent may compress nearby blood vessels and create tissue hypoxia. Hypoxia-inducible factor-1α (HIF-1α) is a key transcription factor produced by tumor cells in response to a low-oxygen environment[29]. It increases the expression of several genes involved in the hypoxia response, including GLUT-1[30]. Higher GLUT-1 expression in tumor tissue reflects increased glycolytic metabolism and is often seen under conditions like ischemia or hypoxia, which cause greater dependence on glycolysis for energy[31]. Previous studies suggest that GLUT-1 expression plays a key role in helping tumor cells survive by maintaining energy supply[32].
This study aimed to compare and analyze the changes in GLUT-1 and Ki-67 between tumor biopsy specimens obtained before SEMS placement and postoperative tissue specimens, to explore the impact of SEMS placement on the tumor microenvironment. The study found that GLUT-1 had a significantly higher expression rate in tumor tissues after SEMS placement (43.7%) compared to before placement (14.1%), and this difference was statistically significant (P < 0.001), while Ki-67 expression showed no significant change. The increased demand for glucose uptake and glycolysis by tumor cells for energy required for growth, proliferation, and invasion primarily relies on GLUT-1[33]. The changes in GLUT-1 expression suggest that SEMS placement has some degree of influence on the tumor metabolism.
When exploring the relationship between GLUT-1 and Ki-67 expression and clinicopathological factors in this study, only a significant correlation was found between high expression of GLUT-1 after SEMS placement and vascular invasion (P = 0.003), while it was not associated with other clinicopathological factors. Studies on primary esophageal cancer by Sawayama et al[34] found that GLUT-1 expression was associated with tumor vascular invasion and microvessel density in the tumor bed. Further research revealed its association with the occurrence of hematogenous metastasis in patients but not with lymph node metastasis. This suggests that GLUT-1 expression is one of the important factors for hematogenous metastasis in tumors. Currently, the mechanism of GLUT-1 expression and tumor hematogenous metastasis is not clear. The hypoxic microenvironment of tumor tissue can lead to an increase in HIF-1α[35]. HIF-1α can mediate the expression of vascular endothelial growth factor, promoting tumor angiogenesis, and can also upregulate GLUT-1 expression, ultimately promoting tumor progression[36]. In this study, the pressure exerted by the SEMS on the tumor bed's blood vessels is likely to exacerbate the hypoxic state of the tumor microenvironment, and the resulting changes in the tumor microenvironment may be one of the reasons for the correlation between high GLUT-1 expression and vascular invasion.
The prognosis of patients after SEMS placement for obstructive CRC is a significant concern for clinical practitioners. Patients with obstructive CRC tend to be diagnosed at later stages, with a majority being in stage III, as reported by Lohsiriwat et al[37], where over 60% of 818 patients were in stage III. In this study, 25 cases (35.2%) were in stage II, and 46 cases (64.8%) were in stage III, with no stage I patients. All patients received postoperative chemotherapy with the XELOX regimen for six months, and the 3-year RFI rate was 68%. The study found that patients with high GLUT-1 expression in tumor tissues before SEMS placement had a 3-year RFI of 40.0%, which was lower than that of low-expression patients at 72.3%. Similarly, in tumor tissues after SEMS placement, patients with high GLUT-1 expression had a 3-year RFI of 45.5%, which was lower than that of low-expression patients at 85.7%. These differences were statistically significant (all P < 0.05). Cox regression analysis showed that both pre-SEMS placement and post-SEMS placement GLUT-1 expression were independent prognostic risk factors for patients.
GLUT-1 has been confirmed as a rate-limiting factor for glucose transport in malignant tumor cells and is highly expressed in many human tumors[20]. The expression of GLUT-1 is significantly upregulated in both primary and metastatic CRC compared to normal tissue; however, the association between this overexpression and prognosis varies across different sites. The study conducted by Furudoi et al[38] revealed that the expression of GLUT-1 at the deepest site of tumor invasion could serve as a valuable prognostic indicator for advanced CRC, indicating a heightened malignant potential and unfavorable prognosis. However, the upregulation of GLUT-1 in liver metastases of CRC implied a favorable prognosis[39]. So far, there has been no definitive indicator to reflect the prognosis after SEMS placement for obstructive CRC. The results of our study indicate that elevated GLUT-1 expression in tumor tissues of obstructive CRC is associated with a poor prognosis. The findings of our study align closely with those reported by Furudoi et al[38]. For patients with high expression in pre-SEMS biopsy, preoperative intensified treatment should be considered to improve long-term prognosis. In our center, for obstructive colon cancer patients after SEMS placement, two cycles of mFolfox6 chemotherapy were administered during the interval between SEMS placement and surgical resection, and the study showed that this treatment approach is safe and reliable, with no recurrence or metastasis in the short term after surgery, with long-term outcomes pending follow-up[40]. Patients with high expression after SEMS placement should receive intensified treatment and close follow-up. In particular, increased attention should be given to patients who exhibit low expression in pre-SEMS placement and elevated expression in post-SEMS placement. Wang et al[41] found that high expression of TrpC5/GLUT-1 is closely related to chemoresistance in advanced CRC. For patients with high GLUT-1 expression after surgery, a first-line chemotherapy regimen alone may not be effective. Genetic testing of the tumor, analysis of mutations in genes such as RAS, BRAF, EGFR, and MSI status, should be considered for comprehensive drug treatment selection.
In this study, there was no significant change in the expression of Ki-67 before and after SEMS placement in patients with obstructive colon cancer. This suggests that stent placement may not have a significant impact on tumor cell proliferation. Furthermore, the expression of Ki-67 in both pre-SEMS placement biopsy specimens and post-SEMS placement surgical specimens was not significantly correlated with patients' RFI (all P > 0.05). A meta-analysis by Luo et al[42] that included 34 studies involving 6180 patients with primary CRC and used immunohistochemistry to detect Ki-67 found that high expression of Ki-67 was associated with poor overall survival (HR 1.54, 95%CI: 1.17-2.02) and poor disease-free survival (HR 1.43, 95%CI: 1.12-1.83). However, CRC prognosis is influenced by multiple factors, not solely by tumor cell proliferation[43]. Patient prognosis is also related to other factors such as TNM staging, vascular invasion, neural invasion, lymphocyte infiltration into the tumor, and tumor cell differentiation[44]. Conversely, some studies have found that in CRC patients, the primary tumor with lower Ki-67 expression was associated with the development of metachronous liver or lung metastases, suggesting that even in tumors with low proliferative activity, hematogenous metastasis may occur[45].
Matsuda et al[17] evaluated changes in oncological characteristics in CRC tissues following SEMS insertion, focusing on growth factors, cell cycle regulation, and apoptosis[1]. However, their study included only 25 patients, which limits its generalizability, and the findings are insufficient to guide clinical treatment decisions. In contrast, our study, which involved a larger sample size, examined the impact of stent implantation from the metabolic perspective of tumor progression. GLUT-1 expression may serve as a potential biomarker to guide treatment strategies. Specifically, for patients exhibiting high GLUT-1 expression in pre-SEMS biopsy specimens, intensified preoperative therapy should be considered to improve long-term outcomes. In the study by Matsuda et al[17], the mean interval from SEMS insertion to elective surgery was 15.6 days. In our study, the mean interval was 2.3 ± 0.4 weeks, indicating that the timing between stent placement and surgery was comparable in both investigations. Further comprehensive studies are warranted to determine whether the duration between SEMS insertion and surgery (e.g., 2-4 weeks) influences clinical outcomes compared to shorter or longer intervals.
This study has limitations. Firstly, it is a single-center retrospective study with a small sample size, inevitably introducing confounding factors and selection bias. Secondly, the lack of a control group (non-SEMS patients) limits our ability to determine the specific effects of SEMS on tumor biology. Thirdly, there were relatively few biopsy specimens available before SEMS placement, and the presence of tumor heterogeneity may have affected the immunohistochemical staining and interpretation of results. Fourthly, whether GLUT1 upregulation following SEMS placement is modulated by additional factors requires further investigation. Despite these limitations, the findings of this study can provide insights for future large-scale prospective randomized trials. A larger, multicenter cohort or a prospective study design would help strengthen the reliability of the conclusions.
CONCLUSION
In conclusion, the technique of SEMS placement for obstructive colon cancer appears feasible, yet there remains a lack of conclusive research regarding the influence of stent placement on tumor behavior via mechanical compression. Our study observed an elevation in GLUT-1 expression in tumor tissue following SEMS placement, correlating with a poorer patient prognosis. These findings offer valuable insights into this ongoing debate.
Footnotes
Provenance and peer review: Unsolicited article; Externally peer reviewed.
Peer-review model: Single blind
Specialty type: Gastroenterology and hepatology
Country of origin: China
Peer-review report’s classification
Scientific Quality: Grade B, Grade C
Novelty: Grade B, Grade C
Creativity or Innovation: Grade B, Grade C
Scientific Significance: Grade B, Grade C
P-Reviewer: Liu YX; Pan SJ S-Editor: Qu XL L-Editor: A P-Editor: Yu HG
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