Association between different types of preoperative anemia and tumor characteristics, systemic inflammation, and survival in colorectal cancer

Introduction

Colorectal cancer (CRC) is the world’s third most common malignant tumor and the second most common cause of cancer-related death (Han et al., 2021). Patients with colorectal cancer often have anemia and other symptoms after diagnosis, especially in patients with advanced colorectal cancer (Sinicrope, 2022). Anemia is a common disorder in CRC, with 40%–60% in colon cancer patients and 20%–51% in individuals with rectal cancer (Chapman et al., 2019). The forecast of CRC depends primarily on the tumor stage at diagnosis. With the increase of tumor focus area, the possibility of acute and chronic blood loss increases, and advanced patients are prone to malnutrition anemia when they suffer from tumor consumption for a long time (Gvirtzman et al., 2021). Numerous studies have suggested that the higher the pathological stage of CRC, the higher the probability of anemia (Lipton et al., 2021; Väyrynen et al., 2018). A recent study has highlighted that anemia incidence in CRC patients with Dukes stage C and D is up to 60%–75% (Deng, Weng & Zhang, 2023). According to statistics, the incidence of anemia in patients with gastrointestinal tumors in China is 51.13%, and more than 90% of them have not been given any treatment to correct anemia before finding a malignant tumor (Ciardiello et al., 2022). Thus, there is an urgent clinical need to explore the role of anemia in patients with CRC. However, few studies have evaluated the relationship between clinical and pathological characteristics of colorectal cancer patients and different types of anemia.

Emerging evidence indicates that some patients with colorectal cancer will have a systemic inflammatory consumption reaction, manifested by increased C-reactive protein (CRP) and decreased albumin, thus causing chronic inflammatory anemia (Hampel et al., 2022). Chronic inflammatory anemia is related to circulating cell inflammatory factors, which can be detected in infections, rheumatic diseases, and malignant tumors (Marques, Weiss & Muckenthaler, 2022). Many studies have reported the association between anemia and poor prognosis in colorectal cancer patients (Weng et al., 2022). However, more data are needed to confirm the relationship between essential parameters such as anemia, tumor characteristics, and systemic inflammation. Patients with CRC are usually accompanied by anemia and chronic inflammation symptoms. The most common is microcytic hypochromic anemia caused by iron deficiency (other uncommon causes include thalassemia and chronic disease anemia) (Phipps, Brookes & Al-Hassi, 2021). The causes of normal and large cell anemia are more diverse. Among them, microcytic hypochromic anemia caused by iron deficiency not only increases the demand for allogeneic blood transfusion during the perioperative period but also is closely related to the poor prognosis of tumor patients (Berg et al., 2023). Furthermore, normocytic anemia might increase the demand for perioperative blood transfusion and the incidence of postoperative complications (Holtedahl et al., 2021). Moreover, there is no report on the relationship between different types of anemia and prognosis in patients with colorectal cancer before operation. Therefore, we collected retrospectively collected the medical records of CRC patients in our hospital and carried out a retrospective analysis to explore the relationship between different types of preoperative anemia and characteristic tumor parameters and systemic inflammatory reaction in patients with CRC and explored the prognosis of CRC patients with different types of preoperative anemia.

Materials & Methods

Results

Comparison of preoperative anemia status and tumor marker index of participants

The preoperative anemia rate of colorectal cancer patients was 43.15% (41/95) in this study. Among patients with different types of anemia before the operation, there were statistically significant differences in mGPS scores among the three groups (P < 0.05, Table 3). However, there was no significant difference in CEA, CA199, CA242, CA724, and CA125 (P > 0.05, Table 3). The percentage of patients with CA199 (+) and CA199(−), different mGPS scores, and CEA(−) and CEA (+) among the three groups were demonstrated in Figs. 1, 2 and 3.

Table 3:

Comparison of preoperative anemia status and tumor marker index of participants among the three groups.

Item		n	Non anemia (n = 52)	Microcytic anemia (n = 14)	Normocytic anemia (n = 29)	χ2	P
CEA (µg/L)						2.339	0.196
	(−)	71	43	10	18
	(+)	24	9	4	11
CA199(U/mL)						1.435	0.326
	(−)	83	47	13	23
	(+)	12	5	1	6
CA724(U/mL)						6.871	0.291
	(−)	81	52	10	19
	(+)	14		4	10
CA242(U/mL)						0.765	0.572
	(−)	79	46	11	22
	(+)	16	6	3	7
CA125(U/ mL)						1.284	0.423
	(−)	76	47	10	19
	(+)	19	5	4	10
	mGPS score					0.970	0.000*
	0	39	31	1	7
	1	35	11	7	17
	2	21	10	6	5

DOI: 10.7717/peerj.16293/table-3

Notes:

P-values were obtained using χ2 tests for categorical variables.

The asterisk implies statistical significance.

Survival of colorectal cancer patients with different preoperative anemia types

The follow-up time of 95 patients was 6–60 months, the median follow-up time was 43 months, and the average survival time was 37 months. The 5-year survival rate of the normocytic anemia group was better than the microcytic anemia group. After the Log-rank test, the difference in survival time among the two groups was statistically significant (P = 0.038, Fig. 4).

Discussion

Patients with colorectal cancer usually have anemia and chronic inflammation (Weng et al., 2022). The most common cause is small cell hypochromic anemia caused by iron deficiency (other uncommon causes include thalassemia and chronic disease anemia). In contrast, the causes of normal and large cell anemia are more diverse (Patel, 2022). In this study, we observed an interaction between systemic inflammation and malignant tumors. There is a consensus that long-term chronic inflammation will cause anemia in the body (El Ghouayel et al., 2022). Inflammatory factors induce the production of excessive iron, which closes the iron output channel and reduces iron absorption in the gastrointestinal tract (Altintas et al., 2022). In this study, 95 patients with CRC were grouped according to different types of anemia. The relationship between oncological characteristics and systemic inflammatory reaction of patients with different preoperative anemia was evaluated, and the prognosis of patients was assessed as well.

Previous studies have shown that the decrease of hemoglobin in the blood of patients with colorectal cancer, especially normal cell anemia, is related to systemic inflammation (Jocić et al., 2022). Jocić et al. (2022) studied the pathogenesis of colorectal cancer and found that the development of intestinal dysfunction promoted bacterial translocation, leading to systemic inflammation (Schneider et al., 2018). This study also found that different types of anemia in colorectal cancer were related to the mGPS score. As we all know, the mGPS score is an inflammatory prognosis score, which can reflect chronic inflammation status by evaluating the body’s C-reactive protein and serum albumin (Hacker et al., 2022). This study shows a significant difference in the mGPS score between the non-anemia group and the two types of anemia group. Therefore, systemic inflammation is an essential determinant of hemoglobin in patients with colorectal cancer (Zhao et al., 2018). Giudice & Selleri (2022) showed that small cell anemia was related to tumor T stage and tumor location, so they believed that tumor size and TNM stage could determine a tumor load in the body, and excessive load would also cause the reduction of hemoglobin. Similarly, this study also found that different types of anemia were closely related to tumor location, tumor size, and TNM stage, consistent with Giudice & Selleri’s (2022) study. Auer et al. (2018) also found that compared with the distal colon and rectum, the hemoglobin of patients with proximal colon tumors was significantly lower. Disturbance of colonic microbiota can lead to the occurrence and development of colorectal cancer and interfere with the absorption of nutrients (Gomes et al., 2022).

Iron is the most important factor causing anemia, which is necessary for both prokaryotic and eukaryotic organisms to have cell functions (Chaparro & Suchdev, 2019). Most pathogenic bacteria have enhanced iron capture mechanisms, so they compete with protective bacteria for free iron (Jamwal, Sharma & Das, 2020). The intestinal flora of the proximal colon is abundant. More iron and other nutrients are absorbed than that of the distal colon, and the intestinal flora of men is more active than that of women (Deivita et al., 2021). Therefore, this is consistent with the conclusion of this study. Different types of anemia are closely related to gender and tumor location (Peake & Noguchi, 2022). Early research on the prognostic significance of blood Hb levels in patients with colorectal cancer has been controversial. It has been reported that the prognosis of colorectal cancer patients with anemia during the perioperative period or blood transfusion during operation will have adverse effects (Liu et al., 2022). Similarly, the study of Van Cutsem et al. (2019) believes that active gastrointestinal bleeding is not a risk factor for gastrointestinal malignant tumors, and the increased severity of anemia will not pose a risk to the prognosis of patients with colorectal cancer. The conclusion of this study on the prognosis of preoperative anemia in patients with CRC is significantly different from that of the study of Van Cutsem et al. (2019). We found that the five-year survival rate of the non-anemia group was significantly higher than that of the anemia group, and the multivariate analysis showed that anemia was an independent risk factor affecting the prognosis of colorectal cancer patients. Most studies now believe that preoperative anemia is an independent risk factor for postoperative incidence rate and mortality in surgical patients, which is consistent with the results of this study (Böhm, Schmalzing & Meybohm, 2022). Anemia is a common and significant problem in patients with colorectal cancer (Ploug et al., 2022). Common causes include tumor hemorrhage, malnutrition, chronic inflammation, tumor infiltration of bone marrow, reduction of erythropoietin synthesis, bone marrow suppression caused by cancer treatment among others (Sawayama et al., 2021). The study also found that tumor size, TNM stage, distant metastasis, mGPS score, and Ki-67 were independent risk factors affecting the prognosis of colorectal cancer patients. Other studies have shown that anemia, even mild anemia, is a risk factor for postoperative complications and more extended hospital stays in colorectal cancer patients (Liu et al., 2018). Gaspar, Sharma & Das (2015) believe that anemia will lead to increased tumor hypoxia and increased HIF-1 α Expression and promote the transcription of target genes involved in angiogenesis, proliferation, and metastasis (Voit & Sankaran, 2020). Because intraoperative bleeding may aggravate anemia, correcting preoperative anemia is more critical for colorectal cancer patients undergoing surgery. However, this study also has some limitations. As this study is a single-center retrospective study with a small sample size, a large-scale multicenter study still needs to verify the conclusion.

Conclusions

Anemia is common in colorectal cancer patients. The oncological characteristics of colorectal cancer patients with different types of preoperative anemia are different. Preoperative anemia is an independent risk factor for the prognosis of patients with colorectal cancer. Therefore, clinicians should correct patients’ anemia and systemic inflammation as early as possible in the stage of comprehensive management before operation, to provide a better prognosis for patients with colorectal cancer.

Supplemental Information