Systemic immune-inflammation index and serum lactoferrin: A novel tool for individualized prognostic assessment in elderly colon cancer

Table 1 Representative studies on systemic immune-inflammation index and lactoferrin in colorectal cancer (2020-2026)

Parameter	Ref.	Research type	Test set	Key findings
SII	Sato et al[34]	Retrospective study	86 patients	In patients with obstructive CRC, lower preoperative SII was independently associated with poorer RFS
	Hernandez-Ainsa et al[35]	Retrospective study	428 patients	SII levels were significantly elevated in CRC patients and varied with disease progression, suggesting its potential as an adjunct tool for early diagnosis
	Feier et al[36]	Retrospective study	296 patients	SII levels were significantly higher in colon cancer than in rectal cancer, indicating distinct systemic inflammatory response patterns between these tumor types
	Rimini et al[37]	Prospective study	3810 patients	SII was identified as an independent inflammatory biomarker predicting cancer risk in the general population, including CRC
	Feng et al[38]	Retrospective study	342 patients	SII levels were significantly higher in CRC compared with adenomatous polyps, demonstrating its utility in distinguishing early-stage cancer from benign adenomas
	Polk et al[39]	Retrospective study	170 patients	In colon cancer liver metastases, low SII predicted longer RFS; whereas in rectal cancer liver metastases, high SII independently predicted longer RFS and OS
	Murray et al[40]	Prospective study	181 patients	Elevated SII levels were significantly associated with more aggressive CTC-positive subtypes and poorer prognosis
	Passardi et al[41]	Prospective study	182 patients	High SII was an independent predictor of poor prognosis in metastatic CRC patients treated with chemotherapy plus bevacizumab
	Ma et al[42]	Retrospective study	248 patients	High SII was one of the independent risk factors for postoperative complications in stage II-III colon cancer patients
	Miyamoto et al[43]	Retrospective study	272 patients	The prognostic value of SII in metastatic CRC was influenced by KRAS status: Predictive for OS in KRAS wild-type patients but limited in KRAS-mutant patients
	Zeynelgil et al[44]	Retrospective study	155 patients	Low SII levels were associated with better OS in univariate analysis among metastatic CRC patients
	Wu et al[45]	Retrospective study	344 patients	The combination of SII and ferritin effectively predicted OS after curative surgery for colon cancer
	Zhang et al[46]	Retrospective study	188 patients	SII was an independent predictor of DFS after curative surgery for colon cancer, with high SII indicating poorer prognosis
	Chang et al[47]	Retrospective study	768 patients	In stage II colon cancer patients without adjuvant chemotherapy, SII levels differed significantly between left- and right-sided tumors
	Silaghi et al[48]	Retrospective study	219 patients	In emergency CRC surgery, elevated preoperative SII was associated with a higher risk of severe postoperative complications
LF	Liu et al[49]	Basic study	8 mice	In an AOM/DSS-induced mouse model of colitis-associated CRC, LF exerted both anti-inflammatory and anti-tumor effects
	Tanaka et al[50]	Interventional preclinical study	63 mice	Oral bLF significantly alleviated intestinal inflammation and improved histological injury in an AOM/DSS-induced model
	Elmorshedy et al[51]	Preclinical experimental study	50 mice	LF served as a targeting ligand in engineered NIMDs for oral colon-targeted delivery of docetaxel and atorvastatin, enhancing anti-CRC efficacy and inhibiting key pathways (p-AKT/p-ERK1/2/NF-κB)
	Elhamid et al[25]	Preclinical experimental study	120 mice	LF acted as a natural targeting ligand and drug carrier in a temperature/pH dual-responsive nanostructured microsphere system, enabling colon-targeted delivery of mesalazine and resveratrol, enhancing therapeutic efficacy and inducing tumor apoptosis
	Raval et al[27]	Basic study	63 rats	LF functioned as an efficient targeting ligand by binding to overexpressed lactoferrin receptors on cancer cells, enabling specific drug delivery and reducing systemic toxicity
	Li et al[52]	Basic study	130 mice	LF inhibited CRC progression under hyperglycemic conditions by targeting the WTAP/m6A/NT5DC3/HKDC1 axis
	Yang et al[53]	Basic study	29 mice	LF was used to trigger responsive aggregation and targeted delivery in an oral Ast delivery system, improving therapeutic effects in IBD
	Wei et al[54]	Basic study	-	Modulation of LF release rate in the colon via nanofiber carriers showed that faster release led to stronger inhibition of HCT116 CRC cells proliferation
	Bhattacharya et al[55]	Basic study	-	LF-modified nanoparticles enabled targeted delivery of methotrexate to CRC cells, enhancing antitumor efficacy and reducing systemic toxicity
	Upasana et al[56]	Basic study	36 rats	LF-functionalized nanoparticles specifically recognized CRC cells, improving targeted delivery and therapeutic efficacy of lapatinib while reducing systemic toxicity
	Ramírez-Sánchez et al[57]	Basic study	-	The anti-CRC activity of bLF depended on its glycosylation structure, inhibiting tumor growth via EGFR and ERK/Akt pathways; deglycosylation markedly reduced this effect
	Chen et al[58]	Basic study	3 samples	LF promoted the initiation and progression of LCC by activating the PI3K/AKT signaling pathway

SII: Systemic immune-inflammation index; LF: Lactoferrin; CRC: Colorectal cancer; RFS: Recurrence-free survival; OS: Overall survival; CTC: Circulating tumor cell; KRAS: Kirsten rat sarcoma viral oncogene; DFS: Disease-free survival; AOM: Azoxymethane; DSS: Dextarn sodium suipate; bLF: Bovine lactoferrin; NIMDs: Nano-in-micro delivery systems; IBD: Inflammatory bowel disease; Ast: Astaxanthin; EGFR: Epidermal growth factor receptor; LCC: Left-sided colon cancer.